BICYCLIC AND TRICYCLIC SUBSTITUTED 2-PYRIDINONE

ANTIBACTERIAL COMPOUNDS

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Patent Provisional Application No.

62/048,166, filed September 9, 2014, the contents of which are incorporated by reference herein.

FIELD OF THE INVENTION

The present description relates to substituted 2-pyridinone compounds and forms and pharmaceutical compositions thereof and methods of using such compounds, forms or compositions thereof for treating or ameliorating Neisseria gonorrhoeae (N. gonorrhoeae). More particularly, the present description relates to bicyclic and tricyclic ring substituted 2-pyridinone compounds and forms and pharmaceutical compositions thereof and methods of using such compounds, forms or compositions thereof for treating or ameliorating a wild-type or drug-resistant form of N. gonorrhoeae.

BACKGROUND

Neisseria is a large genus of generally commensal Gram-negative bacteria that colonize the mucosal surfaces of many animals. The facile ability of N. gonorrhoeae to develop drug resistance makes N. gonorrhoeae a rapidly emerging global health threat, and is considered to be an emerging superbug. 820,000 new cases of N. gonorrhoeae are estimated to occur in the United States every year. With more than 100 million cases of

N. gonorrhoeae reported worldwide, about 12% of drug-resistant N. gonorrhoeae is estimated to be penicillin resistant (penicillin ), about 23% is estimated to be tetracycline resistant (tetracycline R ) and about 13% is estimated to be quinolone resistant (quinolone R ). The level of quinolone resistance in Taiwan and China is about 90% (Morbidity and

Mortality Weekly, Feb 15, 2013). Other forms of drug-resistant N. gonorrhoeae include streptomycin-resistant (streptomycin R ), ciprofloxacin-resistant (ciprofloxacin R ) and ampicillin-resistant (ampicillin ). Currently, ceftriaxone (a cephalosporin) is the drug of last resort for treating N. gonorrhoeae. With few clinical trials underway for new drugs targeting N. gonorrhoeae, the discovery of new antibacterial agents to treat wild-type or drug-resistant forms of N. gonorrhoeae is urgently needed. Although quinolones have been highly effective agents in the clinic, wide-scale deployment and generic usage of second generation quinolones (e.g., ciprofloxacin) has jeopardized their future long-term utility. Furthermore, fluoroquinolones had become the standard of care for treating N. gonorrhoeae in early 1999. As early as 2001, though, bacterial resistance to these agents was also on the rise. Within 6 years, N. gonorrhoeae resistance in certain patient populations went from less than 1% to greater than 40%. In 2007, the Centers for Disease Control (CDC) discontinued the use of ciprofloxacin as the standard of care for treating N. gonorrhoeae. Therefore, new drugs targeting wild-type or drug-resistant forms of N. gonorrhoeae would be expected to help address this important unmet medical need.

As resistance to marketed antibacterial agents continues to increase and new antibacterial agents have not been readily forthcoming from the pharmaceutical industry, the availability of new agents is essential to overcome pre-existing and burgeoning resistance. More particularly, an effective, orally deliverable monotherapy and novel compounds active against wild- type or drug-resistant forms of N. gonorrhoeae are urgently needed. New compounds and new therapies with combinations of antibacterial and antibiotic agents having additive or synergistic activities, including combinations with current agents, would enable longer clinical lifetimes for proven agents against N. gonorrhoeae. Accordingly, the availability of such compounds and therapies would provide a significant current and future human health benefit with a high probability of success on several fronts for the control of wild-type or drug-resistant forms of N. gonorrhoeae for a number of years to come.

All other documents referred to in the present application are incorporated by reference as though fully set forth herein.

SUMMARY The present description relates to a compound of Formula (I):

(I) wherein R _1; R ₂ and R ₃ are as defined herein, and forms and compositions thereof, and also relates to uses of a compound of Formula (I) or a form thereof and methods for treating or ameliorating Neisseria gonorrhoeae (N. gonorrhoeae) in a subject in need thereof, comprising, administering an effective amount of the compound to the subject.

In particular, the present description relates to a compound of Formula (I), and forms and compositions thereof, and to uses of a compound of Formula (I), and forms and compositions thereof, and methods for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising, administering an effective amount of the compound, and forms and compositions thereof, to the subject.

The present description also relates to a compound of Formula (I) or a form thereof having activity against wild- type or drug-resistant forms of N. gonorrhoeae.

In particular, the present description relates to a compound of Formula (I) or a form thereof having activity against wild-type or drug-resistant forms of N. gonorrhoeae.

The present description also relates to a compound of Formula (I) or a form thereof having activity against wild- type forms of N. gonorrhoeae.

In particular, the present description relates to a compound of Formula (I) or a form thereof having activity against wild- type forms of N. gonorrhoeae.

The present description also relates to a compound of Formula (I) or a form thereof having activity against drug-resistant forms of N. gonorrhoeae.

In particular, the present description relates to a compound of Formula (I) or a form thereof having activity against drug-resistant forms of N. gonorrhoeae.

The present description also relates to a compound of Formula (I) or a form thereof having activity against N. gonorrhoeae resistant to one or more known antibacterial or antibiotic agents, wherein drug resistance may be classified as intermediate resistance (IR), high level resistance (HLR), multi-drug resistant (MDR), multi-drug intermediate resistant (MD ^∑ R) or extensively drug resistant (XDR).

More particularly, the present description relates to a compound of Formula (I) or a form thereof having activity against a IR, HLR, MDR, MD ^∑ R or XDR form of

N. gonorrhoeae .

The present description also relates to a compound of Formula (I) or a form thereof having activity against an aminoglycoside-resistant, beta-lactam-resistant, cephalosporin- resistant, macrolide-resistant, quinolone-resistant or tetracycline-resistant form of

N. gonorrhoeae . The present description further relates to a compound of Formula (I) or a form thereof in combination with known agents having additive or synergistic activity, thus providing a combination product for the treatment of N. gonorrhoeae.

The present description further relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating wild- type or drug-resistant forms of N. gonorrhoeae.

More particularly, the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating wild- type forms of N. gonorrhoeae.

More particularly, the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating drug-resistant forms of N. gonorrhoeae.

The present description also relates to use of the compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae resistant to one or more known antibacterial or antibiotic agents, wherein drug resistance may be classified as intermediate resistance (IR), high level resistance (HLR), multi-drug resistant (MDR), multi-drug intermediate resistant (MD ^∑ R) or extensively drug resistant (XDR).

More particularly, the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating IR, HLR, MDR, MD ^∑ R or XDR forms of N. gonorrhoeae.

The present description also relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating an aminoglycoside-resistant, beta-lactam-resistant, cephalosporin-resistant, macrolide-resistant, quinolone-resistant or tetracycline-resistant form of N. gonorrhoeae.

The present description further relates to use of a compound of Formula (I) or a form thereof in combination with known agents having additive or synergistic activity, thus providing a combination product for the treatment of N. gonorrhoeae. DETAILED DESCRIPTION

The present description relates to substituted 2-pyridinone compounds selected from a compound of Formula (I):

(I)

or a form thereof, wherein

Ri is a bicyclic or tricyclic ring system selected from the group consisting

wherein "*" represents a point of attachment for Ri to the 2-pyridinone of Formula (I); and, wherein Ri is substituted on available valences with one to five substituents each selected from R ₅ ;

R ₂ is hydrogen, cyano, Ci_ ₈ alkyl, hydroxyl-Ci_ ₈ alkyl, formyl-Ci_ ₈ alkyl, Ci-galkoxy-Ci-galkyl,

Ci-galkoxy, C ₂ _galkenyl, C ₂ _galkynl, carboxyl, amino-Ci_galkyl, aryl or C3_i ₄ cycloalkyl; R ₃ is hydrogen, hydroxyl, Ci_galkoxy or amino;

R ₅ is hydrogen, halogen, hydroxyl, oxo, cyano, nitro, Ci_galkyl, hydroxyl-Ci-galkyl,

halo-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, Ci-galkyl-thio, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, C ₂ _galkenyl- amino, (C ₂ _galkenyl) ₂ -amino, C ₂ _galkynyl-amino, (C ₂ _galkynyl) ₂ -amino, amino-Ci-galkyl, Ci-ioalkyl-amino-Ci-galkyl,

(C ₁ - ₁ oalkyl) ₂ -amino-C ₁ _galkyl, C^galkenyl-amino-Ci-galkyl,

(C ₂ _galkenyl) ₂ -amino-C ₁ _galkyl, C^galkynyl-amino-Ci-galkyl,

(C ₂ _galkynyl) ₂ -amino-C ₁ _galkyl, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,

Ci-galkoxy-Ci-galkyl-amino, (Ci-galkoxy-Ci-galky^Ci-galky^-amino,

(C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino, Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl,

(C ₁ -galkoxy-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl-amino,

(amino-Ci-galky^Ci-galky^amino, Ci-galkyl-amino-Ci-galkyl-amino,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, amino-Ci-galkyl-amino-Ci-galkyl, (amino-Ci-galky^Ci-galky^amino-Ci-galkyl, (amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino-C ₁ _galkyl,

[(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl,

(C ₁ -galkyl-amino-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, hydroxyl-Ci-galkyl-amino,

(hydroxyl-Ci-galky^Ci-galky^amino, (hydroxyl-C ₁ _galkyl) ₂ -amino,

hydroxyl-Ci-galkyl-amino-Ci-galkyl, (hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(hydroxyl-Ci-galkyl-amino-Ci-galky^Ci-galky^amino,

(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl-amino,

[(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galky^Ci-galky^amin o,

(Ci-galkyl-carbony^Ci-galky^amino-Ci-galkyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-amino-Ci-galkyl-carbonyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-carbonyl, Cs-ncycloalkyl, Cs-ncycloalkyl-Ci-galkyl, Cs-ncycloalkyl-oxy, Cs-ncycloalkyl-Ci-galkoxy, Cs-wcycloalkyl-amino,

Cs-^cycloalkyl-amino-Ci-galkyl, (Cs-^cycloalky^Ci-galky^amino-Ci-galkyl, (C3- ₁₄ cycloalkyl) ₂ -amino-C ₁ _galkyl, Cs-wcycloalkyl-Ci-galkyl-amino-Ci-galkyl, (Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl, (C3_ ₁₄ cycloalkyl-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl, aryl, aryl-Ci-galkyl, aryl-Ci-galkoxy, aryl-amino, (aryl) ₂ -amino, aryl-amino-Ci-galkyl,

(ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino, (aryl-C ₁ _galkyl) ₂ -amino,

aryl-Ci-galkyl-amino-Ci-galkyl, (aryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroary^Ci-galky^amino-Ci-galkyl, (heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-oxy, heterocyclyl-Ci-galkoxy, heterocyclyl-amino, (heterocyclyl) ₂ -amino, heterocyclyl-amino-Ci-galkyl, (heterocycly^Ci-galky^amino-Ci-galkyl,

(heterocyclyl) ₂ -amino-C ₁ _galkyl,

(heterocycly^Cs- _H cycloalkyl-Ci-galky^amino-Ci-galkyl,

heterocyclyl-Ci-galkyl-amino-Ci-galkyl,

(heterocyclyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heterocyclyl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl-oxy-amino,

(heterocyclyl-oxy^i-galky^amino, (heterocyclyl-oxy) ₂ -amino,

(heterocyclyl-oxy-Ci-galky^Ci-galky^amino, heterocyclyl-carbonyl or

heterocyclyl-carbonyl-oxy;

wherein each instance of Cs-ncycloalkyl, aryl, heterocyclyl is optionally substituted with one, two or three substituents each selected from R ₆ ; and,

R ₆ is azido, halogen, hydroxyl, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxyl-Ci-galkyl, Ci-galkoxy-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, hydroxyl-Ci-galkoxy, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl-amino, (amino-Ci-galky^Ci-galky^amino,

Ci-galkyl-amino-Ci-galkyl-amino, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl, Ci-galkyl-amino-Ci-galkyl, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, [(C ₁ _galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl, Ci-galkyl-thio, amino-carbonyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-carbonyl-amino, (carboxyl-Ci-galky^Ci-galky^amino-carbonyl-amino, C ₃ _i ₄ cycloalkyl, Cs- _H cycloalkyl-amino, aryl, aryl-Ci_galkyl, aryl-amino, (aryl,Ci_galkyl)amino, (aryl) ₂ -amino, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino,

(aryl-Ci-galkyl amino, aryl-Ci-galkyl-amino-Ci-galkyl,

(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl, (aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl-amino-Ci-galkyl, (ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-amino-carbonyl, aryl-Ci-galkoxy, aryl-Ci-galkoxy-carbonyl-amino, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, (heteroaryl) ₂ -amino,

heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heteroaryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-amino-Ci-galkyl or heterocyclyl-oxy;

wherein each instance of C ₃ _i ₄ cycloalkyl is optionally substituted with one substituent

selected from R ₉ ; and,

wherein each instance of aryl is optionally substituted with one halogen substituent; and, R ₉ is Ci-galkyl, amino, Ci_galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci_galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to use of a compound of Formula (I) or a form thereof wherein, R5 is:

C ₃ _i ₄ cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from pyrrolyl, thiazolyl, 1H- 1,2,3- triazolyl, lH-tetrazolyl, 2H-tetrazolyl, lH-imidazolyl or pyridinyl; and,

heterocyclyl selected in each instance, when present, from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl,

2,5-dihydro- lH-pyrrolyl, 4,5-dihydro- lH-imidazolyl, 1 ,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl, indolinyl, 2,3- dihydrobenzo[d]oxazolyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, 3,4- dihydroisoquinolin-(lH)-yl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinoxalinyl, (6H)-pyrrolo[3,4-b][l,4]oxazin-(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrolyl, (cis)- octahydrocyclopenta[c]pyrrolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- (lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazinyl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- (2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9- tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3-dihydro-lH- pyrrolo[l,2-a]indolyl, l,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)- l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept- 5-enyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexanyl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexyl, (lR,5S,6s)-3-azabicyclo[3.1.0]hexanyl, (lR,5S)-3- azabicyclo[3.1.0]hexyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexyl, 3,6-diazabicyclo[3.1.0]hexanyl, (lS,5R,6R)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6R)-3-azabicyclo[3.2.0]heptanyl, (lS,5R,6S)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6S)-3-azabicyclo[3.2.0]heptanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptanyl, 2,6- diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7- diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decyl, 2- azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl or 2,8-diazaspiro[4.5]decanyl.

The present description further relates to use of a compound of Formula (I) or a form thereof wherein, R ₅ is:

Cs-^cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl; aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from IH-pyrrol-l-yl, thiazol-2-yl, 1H-

1,2,3-triazol-l-yl, lH-tetrazol-5-yl, 2H-tetrazol-2-yl, lH-imidazol-l-yl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl; or,

heterocyclyl selected in each instance, when present, from azetidin-l-yl, tetrahydrofuran-2-yl, pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-l-yl, piperazin-2-yl, morpholin-4-yl, 1,4- diazepan-l-yl, l,3-dioxolan-2-yl, 2,5-dihydro-lH-pyrrol-l-yl, 4,5-dihydro-lH- imidazol-2-yl, 1 ,4,5,6-tetrahydropyrimidin-2-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-6-yl, indolinyl, 2,3-dihydrobenzo[d]oxazol-6-yl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-4-yl,

3.4- dihydroisoquinolin-2(lH)-yl, 1,2,3,4-tetrahydroisoquinolin-l-yl, 1,2,3,4- tetrahydroquinoxalin-l-yl, (6H)-pyrrolo[3,4-b][l,4]oxazin-6(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-6(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-4(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrol-2-yl, (cis)- octahydrocyclopenta[c]pyrrol-4-yl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(lH)- yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- 2(lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazin-4-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-6(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- 6(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, (4aR,7aR)- hexahydro-lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridin- 6-yl, 2,3,4,9-tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3- dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, 1 ,3-dihydro-2H-isoindol-2-yl, octahydro-2H- isoindol-2-yl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-lH- isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl,

2.5- diazabicyclo[2.2.1]hept-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2- azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hex-3-yl, 3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S,6s)-3-azabicyclo[3.1.0]hex-3-yl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S)-3-azabicyclo[3.1.0]hex-6-yl, (lR,5S)-3- azabicyclo[3.1.0]hexan-6-yl, 3,6-diazabicyclo[3.1.0]hex-3-yl, 3,6- diazabicyclo[3.1.0]hexan-3-yl, (lS,5R,6R)-3-azabicyclo[3.2.0]hept-3-yl, (1S,5R,6S)- 3-azabicyclo[3.2.0]hept-3-yl, (lS,5R)-3-azabicyclo[3.2.0]heptan-3-yl, 5- azaspiro[2.4]hept-5-yl, 5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]dec-2-yl, 2- azaspiro[4.5]decan-2-yl, 2,8-diazaspiro[4.5]dec-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein:

R ₂ is hydrogen, cyano, Ci-galkyl, hydroxyl-Ci_galkyl, formyl-Ci_galkyl, Ci-galkoxy-Ci-galkyl, Ci-galkoxy, C ₂ _galkenyl, C ₂ _galkynl, carboxyl, amino-Ci-galkyl, aryl or C ₃ -i ₄ cycloalkyl; R ₃ is hydrogen, hydroxyl, Ci-galkoxy or amino;

R5 is hydrogen, halogen, cyano, Ci-galkyl, hydroxyl-Ci_galkyl, halo-Ci_galkyl,

(Ci_galkyl) ₂ -amino, amino-Ci-galkyl, Ci_ioalkyl-amino-Ci_galkyl,

(C ₁ - ₁ oalkyl) ₂ -amino-C ₁ -galkyl, Ci-galkyl-amino-Ci-galkyl-carbonyl,

(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-carbonyl or heterocyclyl-Ci_galkyl;

wherein heterocyclyl is optionally substituted with one, two or three substituents each

selected from R ₉ ; and,

R9 is Ci-galkyl, amino, Ci-galkyl-amino, (Ci_galkyl) ₂ -amino, amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl, (Ci-galkyl) ₂ -amino-Ci_galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R _la , and R _lc is selected from a R _lal , Ri _b i and R _lcl ring system, respectively:

wherein "*" represents a point of attachment for R _lal , Ri _b i and R _lcl to the 2-pyridinone of Formula (I); and,

wherein R _5a , R _5b , R _5c and R _5d , when present, are selected from the group consisting of: hydrogen, halogen, hydroxyl, cyano, nitro, Ci-galkyl, hydroxyl-Ci-galkyl, halo-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, Ci-galkyl-thio, carboxyl, Ci-galkyl-carbonyl,

Ci-galkoxy-carbonyl, amino-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, C ₂ _galkenyl- amino, (C ₂ _galkenyl) ₂ -amino, C ₂ _galkynyl-amino, (C ₂ _galkynyl) ₂ -amino, amino-Ci-galkyl, Ci-ioalkyl-amino-Ci-galkyl, (C ₁ _ ₁ oalkyl) ₂ -amino-C ₁ _galkyl, C^galkenyl-amino-Ci-galkyl, (C ₂ _galkenyl) ₂ -amino-C ₁ _galkyl,

C^galkynyl-amino-Ci-galkyl, (C ₂ _galkynyl) ₂ -amino-C ₁ _galkyl, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl,

(halo-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkoxy-Ci-galkyl-amino,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino, (C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino,

Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl,

(C ₁ -galkoxy-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl-amino,

(amino-Ci-galky^Ci-galky^amino, Ci-galkyl-amino-Ci-galkyl-amino,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ _galkyl]amino, amino-Ci-galkyl-amino-Ci-galkyl, (amino-Ci-galky^Ci-galky^amino-Ci-galkyl, (amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl-amino-C ₁ _galkyl,

[(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl,

(C ₁ _galkyl-amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, hydroxyl-Ci-galkyl-amino,

(hydroxyl-Ci-galky^Ci-galky^amino, (hydroxyl-C ₁ _galkyl) ₂ -amino,

hydroxyl-Ci-galkyl-amino-Ci-galkyl, (hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(hydroxyl-Ci-galkyl-amino-Ci-galky^Ci-galky^amino,

(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl-amino,

[(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galky^Ci-galky^amino,

(Ci-galkyl-carbony^Ci-galky^amino-Ci-galkyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-amino-Ci-galkyl-carbonyl, (C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl-carbonyl, Cs-ncycloalkyl, Cs-ncycloalkyl-Ci-galkyl, Cs-ncycloalkyl-oxy, Cs-ncycloalkyl-Ci-galkoxy, Cs-wcycloalkyl-amino,

Cs-^cycloalkyl-amino-Ci-galkyl, (Cs-wcycloalky^Ci-galky^amino-^galkyl,

(C ₃ - ₁₄ cycloalkyl) ₂ -amino-C ₁ _ ₈ alkyl, Cs-wcycloalkyl-^galkyl-amino-^galkyl, (Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₃ _ ₁₄ cycloalkyl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl, aryl-Ci-galkyl, aryl-Ci-galkoxy, aryl-amino, (aryl,^galkyl)amino, (aryl) ₂ -amino, aryl-amino-Ci-galkyl,

(ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino, (aryl-C ₁ _galkyl) ₂ -amino,

aryl-Ci-galkyl-amino-Ci-galkyl, (aryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(aryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroary^Ci-galky^amino-Ci-galkyl, (heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-oxy, heterocyclyl-Ci-galkoxy, heterocyclyl-amino, (heterocyclyl) ₂ -amino, heterocyclyl-amino-Ci-galkyl, (heterocycly^Ci-galky^amino-Ci-galkyl,

(heterocyclyl) ₂ -amino-C ₁ _galkyl,

(heterocycly^Cs-wcycloalkyl-Ci-galky^amino-Ci-galkyl,

heterocyclyl-Ci-galkyl-amino-Ci-galkyl,

(heterocyclyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heterocyclyl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl-oxy-amino,

(heterocyclyl-oxy^i-galky^amino, (heterocyclyl-oxy) ₂ -amino,

(heterocyclyl-oxy-Ci-galky^Ci-galky^amino, heterocyclyl-carbonyl or

heterocyclyl-carbonyl-oxy;

wherein each instance of Cs-ncycloalkyl, aryl, heterocyclyl is optionally substituted with one, two or three substituents each selected from R ₆ ; and,

R ₆ is azido, halogen, hydroxyl, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxyl-Ci-galkyl, Ci-galkoxy-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, hydroxyl-Ci-galkoxy, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl-amino, (amino-Ci-galky^Ci-galky^amino,

Ci-galkyl-amino-Ci-galkyl-amino, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, halo-Ci-galkyl-amino, (halo-C ₁ _ ₈ alkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _galkyl, amino-Ci_galkyl, Ci-galkyl-amino-Ci-galkyl, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, [(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl, Ci-galkyl-thio, amino-carbonyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci_galkyl-carbonyl-amino,

(carboxyl-Ci-galky^Ci-galky^amino-carbonyl-amino, C ₃ _i ₄ cycloalkyl,

Cs-^cycloalkyl-amino, aryl, aryl-Ci-galkyl, aryl-amino, (aryl,Ci-galkyl)amino, (aryl) ₂ -amino, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino,

(aryl-C ₁ _galkyl) ₂ -amino, aryl-Ci-galkyl-amino-Ci-galkyl,

(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl, (aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl-amino-Ci-galkyl, (ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-amino-carbonyl, aryl-Ci-galkoxy, aryl-Ci-galkoxy-carbonyl-amino, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, (heteroaryl) ₂ -amino,

heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heteroaryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl, heterocyclyl-Ci_galkyl, heterocyclyl-amino-Ci-galkyl or heterocyclyl-oxy;

wherein each instance of Cs-^cycloalkyl is optionally substituted with one substituent

selected from R ₉ ; and,

wherein each instance of aryl is optionally substituted with one halogen substituent; and, R ₉ is Ci-galkyl, amino, Ci_galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci_galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , R ₅ b, R _5c and R ₅ d substituted on a R _lal , Ribi and R _lcl ring system is: C ₃ _i ₄ cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from pyrrolyl, thiazolyl, 1H- 1,2,3- triazolyl, lH-tetrazolyl, 2H-tetrazolyl, lH-imidazolyl or pyridinyl; and, heterocyclyl selected in each instance, when present, from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl, 2,5-dihydro- IH-pyrrolyl, 4,5-dihydro- IH-imidazolyl, 1 ,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl, indolinyl, 2,3- dihydrobenzo[d]oxazolyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, 3,4- dihydroisoquinolin-(lH)-yl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinoxalinyl, (6H)-pyrrolo[3,4-b][l,4]oxazin-(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrolyl, (cis)- octahydrocyclopenta[c]pyrrolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- (lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazinyl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- (2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9- tetrahydro- lH-carbazolyl, 1 ,2,3,4-tetrahydropyrazino[ 1 ,2-a]indolyl, 2,3-dihydro- 1H- pyrrolo[l,2-a]indolyl, l,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)- l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept- 5-enyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexanyl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexyl, (lR,5S,6s)-3-azabicyclo[3.1.0]hexanyl, (lR,5S)-3- azabicyclo[3.1.0]hexyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexyl, 3,6-diazabicyclo[3.1.0]hexanyl, (lS,5R,6R)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6R)-3-azabicyclo[3.2.0]heptanyl, (lS,5R,6S)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6S)-3-azabicyclo[3.2.0]heptanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptanyl, 2,6- diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7- diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decyl, 2- azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl or 2,8-diazaspiro[4.5]decanyl.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , R _5c and R ₅ d substituted on a R _lal , Ribi and R _lcl ring system is:

Cs-ncycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from IH-pyrrol-l-yl, thiazol-2-yl, 1H-

1,2,3-triazol-l-yl, lH-tetrazol-5-yl, 2H-tetrazol-2-yl, lH-imidazol-l-yl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl; or,

heterocyclyl selected in each instance, when present, from azetidin-l-yl, tetrahydrofuran-2-yl, pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-l-yl, piperazin-2-yl, morpholin-4-yl, 1,4- diazepan-l-yl, l,3-dioxolan-2-yl, 2,5-dihydro-lH-pyrrol-l-yl, 4,5-dihydro-lH- imidazol-2-yl, 1 ,4,5,6-tetrahydropyrimidin-2-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-6-yl, indolinyl, 2,3-dihydrobenzo[d]oxazol-6-yl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-4-yl, 3,4-dihydroisoquinolin-2(lH)-yl, 1,2,3,4-tetrahydroisoquinolin-l-yl, 1,2,3,4- tetrahydroquinoxalin- 1-yl, (6H)-pyrrolo[3,4-b] [ 1 ,4] oxazin-6(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-6(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-4(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrol-2-yl, (cis)- octahydrocyclopenta[c]pyrrol-4-yl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(lH)- yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- 2(lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazin-4-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-6(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- 6(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, (4aR,7aR)- hexahydro-lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridin- 6-yl, 2,3,4,9-tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3- dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, 1 ,3-dihydro-2H-isoindol-2-yl, octahydro-2H- isoindol-2-yl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-lH- isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl, 2,5-diazabicyclo[2.2.1]hept-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2- azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hex-3-yl, 3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S,6s)-3-azabicyclo[3.1.0]hex-3-yl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S)-3-azabicyclo[3.1.0]hex-6-yl, (lR,5S)-3- azabicyclo[3.1.0]hexan-6-yl, 3,6-diazabicyclo[3.1.0]hex-3-yl, 3,6- diazabicyclo[3.1.0]hexan-3-yl, (lS,5R,6R)-3-azabicyclo[3.2.0]hept-3-yl, (1S,5R,6S)- 3-azabicyclo[3.2.0]hept-3-yl, (lS,5R)-3-azabicyclo[3.2.0]heptan-3-yl, 5- azaspiro[2.4]hept-5-yl, 5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]dec-2-yl, 2- azaspiro[4.5]decan-2-yl, 2,8-diazaspiro[4.5]dec-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R _la , R _¾ and R _lc is selected from the R _lal , Ri _b i and R _lcl ring system, respectively, and R _5a , R _5b , R _5c and R _5d , when present, are selected from the group consisting of:

hydrogen, halogen, cyano, Ci-galkyl, hydroxyl-Ci-galkyl, halo-Ci-galkyl, amino-Ci-galkyl,

Ci-ioalkyl-amino-Ci-galkyl, (Ci-ioalkyl amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl-carbonyl, (Ci-galkyl amino-Ci-galkyl-carbonyl or heterocyclyl-Ci-galkyl;

wherein heterocyclyl is optionally substituted with one, two or three substituents each

selected from R ₉ ; and,

R ₉ is Ci-galkyl, amino, Ci-galkyl-amino, (Ci-galkyl amino, amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein Rs _a , Rs , R _5c and Rsa substituted on a R _lal , R^i and R _lcl ring system is:

heterocyclyl selected in each instance, when present, from pyrrolidinyl. The present description also relates to use of a compound of Formula (I) or a form thereof wherein Rs _a , Rs _b , R _5c and Rsa substituted on a R _lal , Ri _b i and R _lcl ring system is:

heterocyclyl selected in each instance, when present, from pyrrolidin-l-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R _la , and R _lc is selected from the R _lal , R^i and R _lcl ring system, respectively, and Rs _a , Rs _b , R _5c and Rsa, when present, are selected from the group consisting of (where "Ring" in the table below indicates whether an R _lal , R^i or R _lcl ring system is selected; and, "— " indicates that one or more of R _5a , R _5b , R _5c or R _5d are not present):

53 Rial CH ₃ H H H wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof. The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R^, Rn and R _lm is selected from a Rm, Rni and R _lml ring system, respectively:

Riki, Rin, and R _lml wherein "*" represents a point of attachment for Rm, Rni and R _lml to the 2-pyridinone of Formula (I); and,

wherein R _5a , R ₅ b, R _5c , Rsa, R _5e and R5 when present, are selected from the group consisting of:

hydrogen, halogen, hydroxyl, cyano, nitro, Ci-galkyl, hydroxyl-Ci-galkyl, halo-Ci-galkyl, Ci- ₈ alkoxy, halo-Ci-galkoxy, Ci-galkyl-thio, carboxyl, Ci-galkyl-carbonyl,

Ci-galkoxy-carbonyl, amino-carbonyl, amino,

C ₂ - ₈ alkenyl- amino, (C ₂ _galkenyl) ₂ -amino, C ₂ _galkynyl-amino, (C ₂ _galkynyl) ₂ -amino, amino-Ci-galkyl, Ci-ioalkyl-amino-Ci-galkyl, (C ₁ _ ₁ oalkyl) ₂ -amino-C ₁ _galkyl,

C^galkenyl-amino-Ci-galkyl, (C ₂ _galkenyl) ₂ -amino-C ₁ _galkyl,

C^galkynyl-amino-Ci-galkyl, (C ₂ _galkynyl) ₂ -amino-C ₁ _galkyl, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl,

(halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkoxy-Ci-galkyl-amino,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino, (C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino,

Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl,

(C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl-amino,

(amino-Ci-galky^Ci-galky^amino, Ci-galkyl-amino-Ci-galkyl-amino,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, amino-Ci-galkyl-amino-Ci-galkyl, (amino-Ci-galky^Ci-galky^amino-Ci-galkyl, (amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino-C ₁ _galkyl,

[(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl,

(C ₁ -galkyl-amino-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, hydroxyl-Ci-galkyl-amino,

(hydroxyl-Ci-galky^Ci-galky^amino, (hydroxyl-C ₁ _galkyl) ₂ -amino,

hydroxyl-Ci-galkyl-amino-Ci-galkyl, (hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(hydroxyl-Ci-galkyl-amino-Ci-galky^Ci-galky^amino,

(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl-amino,

[(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galky^Ci-galky^amin o,

(Ci-galkyl-carbony^Ci-galky^amino-Ci-galkyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-amino-Ci-galkyl-carbonyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-carbonyl, Cs-ncycloalkyl, Cs-ncycloalkyl-Ci-galkyl, Cs-ncycloalkyl-oxy, Cs-ncycloalkyl-Ci-galkoxy, Cs-wcycloalkyl-amino,

Cs-^cycloalkyl-amino-Ci-galkyl, (Cs-^cycloalky^Ci-galky^amino-Ci-galkyl,

(C ₃ - ₁₄ cycloalkyl) ₂ -amino-C ₁ _galkyl, Cs-wcycloalkyl-Ci-galkyl-amino-Ci-galkyl, (Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₃ _ ₁₄ cycloalkyl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl, aryl-Ci-galkyl, aryl-Ci-galkoxy, aryl-amino, (aryl,^galkyl)amino, (aryl) ₂ -amino, aryl-amino-Ci-galkyl,

(ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino, (aryl-C ₁ _galkyl) ₂ -amino,

aryl-Ci-galkyl-amino-Ci-galkyl, (aryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(aryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroary^Ci-galky^amino-Ci-galkyl, (heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-oxy, heterocyclyl-Ci-galkoxy, heterocyclyl-amino, (heterocyclyl) ₂ -amino, heterocyclyl-amino-Ci-galkyl, (heterocycly^Ci-galky^amino-Ci-galkyl,

(heterocyclyl) ₂ -amino-C ₁ _galkyl,

(heterocycly^Cs-wcycloalkyl-Ci-galky^amino-Ci-galkyl,

heterocyclyl-Ci-galkyl-amino-Ci-galkyl,

(heterocyclyl-Ci-galky^Ci-galky^amino-Ci-galkyl, (heterocyclyl-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl, heterocyclyl-oxy-amino,

(heterocyclyl-oxy^i-galky^amino, (heterocyclyl-oxy) ₂ -amino,

(heterocyclyl-oxy-Ci-galky^^galky^amino, heterocyclyl-carbonyl or

heterocyclyl-carbonyl-oxy;

wherein each instance of Cs-ncycloalkyl, aryl, heterocyclyl is optionally substituted with one, two or three substituents each selected from R ₆ ; and,

R ₆ is azido, halogen, hydroxyl, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxyl-Ci-galkyl, Ci-galkoxy-Ci-galkyl, Ci- ₈ alkoxy, halo-Ci-galkoxy, hydroxyl-Ci-galkoxy, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl-amino, (amino-Ci-galky^Ci-galky^amino,

Ci-galkyl-amino-Ci-galkyl-amino, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl, Ci-galkyl-amino-Ci-galkyl, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, [(C ₁ _galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl, Ci-galkyl-thio, amino-carbonyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-carbonyl-amino,

(carboxyl-Ci-galky^Ci-galky^amino-carbonyl-amino, Cs-ncycloalkyl,

(aryl) ₂ -amino, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino,

(aryl-C ₁ _galkyl) ₂ -amino, aryl-Ci-galkyl-amino-Ci-galkyl,

(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl, (aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl-amino-Ci-galkyl, (ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-amino-carbonyl, aryl-Q-galkoxy, aryl-Ci-galkoxy-carbonyl-amino, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, (heteroaryl) ₂ -amino,

heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heteroaryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-amino-Ci-galkyl or heterocyclyl-oxy;

wherein each instance of Cs-^cycloalkyl is optionally substituted with one substituent

selected from R9; and,

wherein each instance of aryl is optionally substituted with one halogen substituent; and, R9 is Ci-galkyl, amino, Ci-galkyl-amino, (C ₁ _ ₈ alkyl) ₂ -amino, amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , Rs _c , R _5d , R _5e and R _5f substituted on a R , R ₁₁₁ and R _lml ring system is:

Cs-ncycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from pyrrolyl, thiazolyl, 1H- 1,2,3- triazolyl, lH-tetrazolyl, 2H-tetrazolyl, lH-imidazolyl or pyridinyl; and,

heterocyclyl selected in each instance, when present, from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl, 2,5-dihydro- lH-pyrrolyl, 4,5-dihydro- lH-imidazolyl, 1 ,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl, indolinyl, 2,3- dihydrobenzo[d]oxazolyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, 3,4- dihydroisoquinolin-(lH)-yl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinoxalinyl, (6H)-pyrrolo[3,4-b][l,4]oxazin-(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrolyl, (cis)- octahydrocyclopenta[c]pyrrolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- (lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazinyl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- (2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9- tetrahydro- lH-carbazolyl, 1 ,2,3,4-tetrahydropyrazino[ 1 ,2-a]indolyl, 2,3-dihydro- 1H- pyrrolo[l,2-a]indolyl, l,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)- l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept- 5-enyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexanyl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexyl, (lR,5S,6s)-3-azabicyclo[3.1.0]hexanyl, (lR,5S)-3- azabicyclo[3.1.0]hexyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexyl, 3,6-diazabicyclo[3.1.0]hexanyl, (lS,5R,6R)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6R)-3-azabicyclo[3.2.0]heptanyl, (lS,5R,6S)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6S)-3-azabicyclo[3.2.0]heptanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptanyl, 2,6- diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7- diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decyl, 2- azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl or 2,8-diazaspiro[4.5]decanyl.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , R ₅ b, R _5c , R ₅ d, R _5e and R ₅ f substituted on a R , Rin and R _lml ring system is:

Cs-ncycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from IH-pyrrol-l-yl, thiazol-2-yl, 1H-

1,2,3-triazol-l-yl, lH-tetrazol-5-yl, 2H-tetrazol-2-yl, lH-imidazol-l-yl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl; or,

heterocyclyl selected in each instance, when present, from azetidin-l-yl, tetrahydrofuran-2-yl, pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-l-yl, piperazin-2-yl, morpholin-4-yl, 1,4- diazepan-l-yl, l,3-dioxolan-2-yl, 2,5-dihydro-lH-pyrrol-l-yl, 4,5-dihydro-lH- imidazol-2-yl, 1 ,4,5,6-tetrahydropyrimidin-2-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-6-yl, indolinyl, 2,3-dihydrobenzo[d]oxazol-6-yl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-4-yl, 3,4-dihydroisoquinolin-2(lH)-yl, 1,2,3,4-tetrahydroisoquinolin-l-yl, 1,2,3,4- tetrahydroquinoxalin- 1-yl, (6H)-pyrrolo[3,4-b] [ 1 ,4] oxazin-6(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-6(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-4(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrol-2-yl, (cis)- octahydrocyclopenta[c]pyrrol-4-yl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(lH)- yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- 2(lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazin-4-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-6(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- 6(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, (4aR,7aR)- hexahydro-lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridin- 6-yl, 2,3,4,9-tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3- dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, 1 ,3-dihydro-2H-isoindol-2-yl, octahydro-2H- isoindol-2-yl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-lH- isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl, 2,5-diazabicyclo[2.2.1]hept-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2- azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hex-3-yl, 3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S,6s)-3-azabicyclo[3.1.0]hex-3-yl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S)-3-azabicyclo[3.1.0]hex-6-yl, (lR,5S)-3- azabicyclo[3.1.0]hexan-6-yl, 3,6-diazabicyclo[3.1.0]hex-3-yl, 3,6- diazabicyclo[3.1.0]hexan-3-yl, (lS,5R,6R)-3-azabicyclo[3.2.0]hept-3-yl, (1S,5R,6S)- 3-azabicyclo[3.2.0]hept-3-yl, (lS,5R)-3-azabicyclo[3.2.0]heptan-3-yl, 5- azaspiro[2.4]hept-5-yl, 5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]dec-2-yl, 2- azaspiro[4.5]decan-2-yl, 2,8-diazaspiro[4.5]dec-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system Ri _k , Rn and R _lm is selected from the R , Rin and R _lml ring system, respectively, and Rs _a , Rs , R _5c , R _5d , R _5e and Rs _f , when present, are selected from the group consisting of:

hydrogen, C _h alky! or (Ci-salkyl amino; wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R^, Rn and R _lm is selected from a Rm, Rni and R _lml ring system, respectively, and Rs _a , Rs , R _5c , R ₅ d, R _5e and R5 when present, are selected from the group consisting of (where "Ring" in the table below indicates whether an Rm, Rm or R _lml ring system is selected; and, "— " indicates that one or more of R _5a , R ₅ b, R _5c , Rsa, R _5e or R ₅ f are not present):

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R^, Rn and Ry is selected from a Rm, Rm and R^ ring system, respectively:

Rihi Rm, and R^, wherein "*" represents a point of attachment for Rm, R and R^ to the 2-pyridinone of Formula (I); and,

wherein Rs _a and Rs , when present, are selected from the group consisting of: hydrogen, halogen, hydroxyl, cyano, nitro, Ci-galkyl, hydroxyl-Ci-galkyl, halo-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, Ci-galkyl-thio, carboxyl, Ci-galkyl-carbonyl,

Ci-galkoxy-carbonyl, amino-carbonyl, amino, Ci-galkyl-amino,

C ₂ -galkenyl- amino, (C ₂ _galkenyl) ₂ -amino, C ₂ _galkynyl-amino, (C ₂ _galkynyl) ₂ -amino, amino-Ci-galkyl, Ci-ioalkyl-amino-Ci-galkyl, (C ₁ _ ₁ oalkyl) ₂ -amino-C ₁ _galkyl,

C^galkenyl-amino-Ci-galkyl, (C ₂ _galkenyl) ₂ -amino-C ₁ _galkyl,

C^galkynyl-amino-Ci-galkyl, (C ₂ _galkynyl) ₂ -amino-C ₁ _galkyl, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl,

(halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkoxy-Ci-galkyl-amino,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino, (C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino,

Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl,

(C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl-amino,

(amino-Ci-galky^Ci-galky^amino, Ci-galkyl-amino-Ci-galkyl-amino,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino,

[(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ _galkyl]amino, amino-Ci-galkyl-amino-Ci-galkyl, (amino-Ci-galky^Ci-galky^amino-Ci-galkyl, (amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl-amino-C ₁ _galkyl,

[(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino-C ₁ _galkyl,

(C ₁ _galkyl-amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, hydroxyl-Ci-galkyl-amino,

(hydroxyl-Ci-galky^Ci-galky^amino, (hydroxyl-C ₁ _galkyl) ₂ -amino,

hydroxyl-Ci-galkyl-amino-Ci-galkyl, (hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl, hydroxyl-Ci-galkyl-amino-Ci-galkyl-amino,

(hydroxyl-Ci-galkyl-amino-Ci-galky^Ci-galky^amino,

(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl-amino,

[(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galky^Ci-galky^amino,

(Ci-galkyl-carbony^Ci-galky^amino-Ci-galkyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-amino-Ci-galkyl-carbonyl,

(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-carbonyl,

Cs-wcycloalkyl-amino,

Cs- _H cycloalkyl-amino-Ci-galkyl, (Cs- _H cycloalky^Ci-galky^amino-Ci-galkyl, (C ₃ _ ₁₄ cycloalkyl) ₂ -amino-C ₁ _ ₈ alkyl, Cs-wcycloalkyl-Ci-galkyl-amino-Ci-galkyl, (Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₃ - ₁₄ cycloalkyl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, aryl, aryl-Ci-galkyl, aryl-Q-galkoxy, aryl-amino, (aryl,^galkyl)amino, (aryl) ₂ -amino, aryl-amino-Ci-galkyl,

(ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino, (aryl-C ₁ _galkyl) ₂ -amino,

aryl-Ci-galkyl-amino-Ci-galkyl, (aryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(aryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroary^Ci-galky^amino-Ci-galkyl, (heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-oxy, heterocyclyl-Ci-galkoxy, heterocyclyl-amino, (heterocyclyl) ₂ -amino, heterocyclyl-amino-Ci-galkyl, (heterocycly^Ci-galky^amino-Ci-galkyl,

(heterocyclyl) ₂ -amino-C ₁ _galkyl,

(heterocycly^Cs-wcycloalkyl-Ci-galky^amino-Ci-galkyl,

heterocyclyl-Ci-galkyl-amino-Ci-galkyl,

(heterocyclyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heterocyclyl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl-oxy-amino,

(heterocyclyl-oxy^i-galky^amino, (heterocyclyl-oxy) ₂ -amino,

(heterocyclyl-oxy-Ci-galky^Ci-galky^amino, heterocyclyl-carbonyl or

heterocyclyl-carbonyl-oxy;

wherein each instance of Cs-^cycloalkyl, aryl, heterocyclyl is optionally substituted with one, two or three substituents each selected from R ₆ ; and,

R ₆ is azido, halogen, hydroxyl, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxyl-Ci-galkyl, Ci-galkoxy-Ci-galkyl, Ci-galkoxy, halo-Ci-galkoxy, hydroxyl-Ci-galkoxy, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl-amino, (amino-Ci-galky^Ci-galky^amino,

Ci-galkyl-amino-Ci-galkyl-amino, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl, Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino-C ₁ _galkyl, Ci-galkyl-thio, amino-carbonyl, Ci-galkyl-amino-carbonyl,

(C ₁ _ ₈ alkyl) ₂ -amino-carbonyl, Ci-galkyl-carbonyl-amino,

(carboxyl-Ci-galky^^galky^amino-carbonyl-amino, Cs-^cycloalkyl,

(aryl) ₂ -amino, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino,

(aryl-C ₁ _galkyl) ₂ -amino, aryl-Ci-galkyl-amino-Ci-galkyl,

(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl, (aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl-amino-Ci-galkyl, (ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-amino-carbonyl, aryl-Ci-galkoxy, aryl-Ci-galkoxy-carbonyl-amino, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, (heteroaryl) ₂ -amino,

heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heteroaryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-amino-Ci-galkyl or heterocyclyl-oxy;

wherein each instance of Cs-^cycloalkyl is optionally substituted with one substituent

selected from R ₉ ; and,

wherein each instance of aryl is optionally substituted with one halogen substituent; and, R9 is Ci-galkyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein Rs _a and Rs substituted on a Rmi, Rm and R _1j1 ring system is:

Cs-ncycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from pyrrolyl, thiazolyl, 1H- 1,2,3- triazolyl, lH-tetrazolyl, 2H-tetrazolyl, lH-imidazolyl or pyridinyl; and,

heterocyclyl selected in each instance, when present, from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl, 2,5-dihydro- lH-pyrrolyl, 4,5-dihydro- lH-imidazolyl, 1 ,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl, indolinyl, 2,3- dihydrobenzo[d]oxazolyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, 3,4- dihydroisoquinolin-(lH)-yl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinoxalinyl, (6H)-pyrrolo[3,4-b][l,4]oxazin-(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-(4aH)-yl, hexahydro- lH-cyclopenta[c]pyrrolyl, (cis)- octahydrocyclopenta[c]pyrrolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- (lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazinyl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- (2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9- tetrahydro- lH-carbazolyl, 1 ,2,3,4-tetrahydropyrazino[ 1 ,2-a]indolyl, 2,3-dihydro- 1H- pyrrolo[l,2-a]indolyl, l,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)- l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept- 5-enyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexanyl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexyl, (lR,5S,6s)-3-azabicyclo[3.1.0]hexanyl, (lR,5S)-3- azabicyclo[3.1.0]hexyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexyl, 3,6-diazabicyclo[3.1.0]hexanyl, (lS,5R,6R)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6R)-3-azabicyclo[3.2.0]heptanyl, (lS,5R,6S)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6S)-3-azabicyclo[3.2.0]heptanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptanyl, 2,6- diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7- diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decyl, 2- azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl or 2,8-diazaspiro[4.5]decanyl. The present description also relates to use of a compound of Formula (I) or a form thereof wherein Rs _a and Rs substituted on a Rmi, Rm and R _1j1 ring system is:

Cs-^cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from IH-pyrrol-l-yl, thiazol-2-yl, 1H-

1,2,3-triazol-l-yl, lH-tetrazol-5-yl, 2H-tetrazol-2-yl, lH-imidazol-l-yl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl; or,

heterocyclyl selected in each instance, when present, from azetidin-l-yl, tetrahydrofuran-2-yl, pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-l-yl, piperazin-2-yl, morpholin-4-yl, 1,4- diazepan-l-yl, l,3-dioxolan-2-yl, 2,5-dihydro-lH-pyrrol-l-yl, 4,5-dihydro-lH- imidazol-2-yl, 1 ,4,5,6-tetrahydropyrimidin-2-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-6-yl, indolinyl, 2,3-dihydrobenzo[d]oxazol-6-yl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-4-yl, 3,4-dihydroisoquinolin-2(lH)-yl, 1,2,3,4-tetrahydroisoquinolin-l-yl, 1,2,3,4- tetrahydroquinoxalin- 1-yl, (6H)-pyrrolo[3,4-b] [ 1 ,4] oxazin-6(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-6(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b][l,4]oxazin-4(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrol-2-yl, (cis)- octahydrocyclopenta[c]pyrrol-4-yl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(lH)- yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- 2(lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazin-4-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-6(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- 6(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, (4aR,7aR)- hexahydro-lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridin- 6-yl, 2,3,4,9-tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3- dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, 1 ,3-dihydro-2H-isoindol-2-yl, octahydro-2H- isoindol-2-yl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-lH- isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl, 2,5-diazabicyclo[2.2.1]hept-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2- azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hex-3-yl, 3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S,6s)-3-azabicyclo[3.1.0]hex-3-yl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S)-3-azabicyclo[3.1.0]hex-6-yl, (lR,5S)-3- azabicyclo[3.1.0]hexan-6-yl, 3,6-diazabicyclo[3.1.0]hex-3-yl, 3,6- diazabicyclo[3.1.0]hexan-3-yl, (lS,5R,6R)-3-azabicyclo[3.2.0]hept-3-yl, (1S,5R,6S)- 3-azabicyclo[3.2.0]hept-3-yl, (lS,5R)-3-azabicyclo[3.2.0]heptan-3-yl, 5- azaspiro[2.4]hept-5-yl, 5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]dec-2-yl, 2- azaspiro[4.5]decan-2-yl, 2,8-diazaspiro[4.5]dec-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system Rm Rn and Ry is selected from the Ri _h i, Rm and R _1j1 ring system, respectively, and Rs _a and Rs , when present, are selected from the group consisting of:

hydrogen or Ci^alkyl;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system Rm Rn and Ry is selected from the R^i, Rm and R _1j1 ring system, respectively, and Rs _a and Rs , when present, are selected from the group consisting of (where "Ring" in the table below indicates whether an Rm, Rm and R^ ring system is selected; and, "— " indicates that one or more of R _5a or R _5b are not present):

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R ₁₍₁ , Ri _e , Ri _f and R _lg is selected from a R ₁₍ JI, R _le i, Rin and R _lgl ring system, respectively:

wherein "*" represents a point of attachment for R ₁₍ JI, R _le i, Rin and R _lgl to the 2-pyridinone of Formula (I); and,

wherein Rs _a , Rs _t ,, R _5c and Rsa, when present, are selected from the group consisting of: hydrogen, halogen, hydroxyl, , cyano, nitro, Ci-galkyl, hydroxyl-Ci-galkyl, halo-Ci-galkyl, Ci- ₈ alkoxy, halo-Ci-galkoxy, Ci-galkyl-thio, carboxyl, Ci-galkyl-carbonyl,

Ci-galkoxy-carbonyl, amino-carbonyl, amino,

C ₂ - ₈ alkenyl- amino, (C ₂ _galkenyl) ₂ -amino, C ₂ _galkynyl-amino, (C ₂ _galkynyl) ₂ -amino, amino-Ci-galkyl, Ci-ioalkyl-amino-Ci-galkyl, (C ₁ _ ₁ oalkyl) ₂ -amino-C ₁ _galkyl,

C^galkenyl-amino-Ci-galkyl, (C ₂ _galkenyl) ₂ -amino-C ₁ _galkyl,

C^galkynyl-amino-Ci-galkyl, (C ₂ _galkynyl) ₂ -amino-C ₁ _galkyl, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl,

(halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkoxy-Ci-galkyl-amino,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino, (C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino,

Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl,

(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl,

(C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl-amino,

(amino-Ci-galky^Ci-galky^amino, Ci-galkyl-amino-Ci-galkyl-amino,

(Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, amino-Ci-galkyl-amino-Ci-galkyl,

(amino-Ci-galky^Ci-galky^amino-Ci-galkyl, (amino-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-amino-C ₁ _galkyl,

[(C ₁ -galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl,

(C ₁ -galkyl-amino-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, hydroxyl-Ci-galkyl-amino,

(hydroxyl-Ci-galky^Ci-galky^amino, (hydroxyl-C ₁ _galkyl) ₂ -amino,

hydroxyl-Ci-galkyl-amino-Ci-galkyl, (hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(hydroxyl-Ci-galkyl-amino-Ci-galky^Ci-galky^amino,

(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galkyl-amino,

[(hydroxyl-Ci-galky^Ci-galky^amino-Ci-galky^Ci-galky^amin o,

(Ci-galkyl-carbony^Ci-galky^amino-Ci-galkyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-amino-Ci-galkyl-carbonyl,

(C ₁ _galkyl) ₂ -amino-C ₁ _galkyl-carbonyl, Cs-ncycloalkyl, Cs-ncycloalkyl-Ci-galkyl, Cs-ncycloalkyl-oxy, Cs-ncycloalkyl-Ci-galkoxy, Cs-wcycloalkyl-amino,

Cs-^cycloalkyl-amino-Ci-galkyl, (Cs-^cycloalky^Ci-galky^amino-Ci-galkyl,

(C ₃ - ₁₄ cycloalkyl) ₂ -amino-C ₁ _galkyl, Cs-wcycloalkyl-Ci-galkyl-amino-Ci-galkyl, (Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(C ₃ _ ₁₄ cycloalkyl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl, aryl-Ci-galkyl, aryl-Ci-galkoxy, aryl-amino, (aryl,^galkyl)amino, (aryl) ₂ -amino, aryl-amino-Ci-galkyl,

(ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino, (aryl-C ₁ _galkyl) ₂ -amino,

aryl-Ci-galkyl-amino-Ci-galkyl, (aryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(aryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroary^Ci-galky^amino-Ci-galkyl, (heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-oxy, heterocyclyl-Ci-galkoxy, heterocyclyl-amino, (heterocyclyl) ₂ -amino, heterocyclyl-amino-Ci-galkyl, (heterocycly^Ci-galky^amino-Ci-galkyl,

(heterocyclyl) ₂ -amino-C ₁ _galkyl,

(heterocycly^Cs-wcycloalkyl-Ci-galky^amino-Ci-galkyl,

heterocyclyl-Ci-galkyl-amino-Ci-galkyl,

(heterocyclyl-Ci-galky^Ci-galky^amino-Ci-galkyl, (heterocyclyl-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl, heterocyclyl-oxy-amino,

(heterocyclyl-oxy^i-galky^amino, (heterocyclyl-oxy) ₂ -amino,

(heterocyclyl-oxy-Ci-galky^^galky^amino, heterocyclyl-carbonyl or

heterocyclyl-carbonyl-oxy;

wherein each instance of Cs-ncycloalkyl, aryl, heterocyclyl is optionally substituted with one, two or three substituents each selected from R ₆ ; and,

R ₆ is azido, halogen, hydroxyl, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxyl-Ci-galkyl, Ci-galkoxy-Ci-galkyl, Ci- ₈ alkoxy, halo-Ci-galkoxy, hydroxyl-Ci-galkoxy, carboxyl, Ci-galkyl-carbonyl, Ci-galkoxy-carbonyl, amino, Ci-galkyl-amino, (C ₁ _galkyl) ₂ -amino, amino-Ci-galkyl-amino, (amino-Ci-galky^Ci-galky^amino,

Ci-galkyl-amino-Ci-galkyl-amino, (Ci-galkyl-amino-Ci-galky^Ci-galky^amino, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-amino, [(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl,C ₁ _galkyl]amino, halo-Ci-galkyl-amino, (halo-C ₁ _galkyl) ₂ -amino, halo-Ci-galkyl-amino-Ci-galkyl, (halo-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, amino-Ci-galkyl, Ci-galkyl-amino-Ci-galkyl, (C ₁ -galkyl) ₂ -amino-C ₁ _galkyl, [(C ₁ _galkyl) ₂ -amino-C ₁ -galkyl,C ₁ -galkyl]amino-C ₁ _galkyl, Ci-galkyl-thio, amino-carbonyl, Ci-galkyl-amino-carbonyl,

(C ₁ _galkyl) ₂ -amino-carbonyl, Ci-galkyl-carbonyl-amino,

(carboxyl-Ci-galky^Ci-galky^amino-carbonyl-amino, Cs-ncycloalkyl,

(aryl) ₂ -amino, aryl-Ci-galkyl-amino, (aryl-Ci-galky^Ci-galky^amino,

(aryl-C ₁ _galkyl) ₂ -amino, aryl-Ci-galkyl-amino-Ci-galkyl,

(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl, (aryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, aryl-amino-Ci-galkyl, (ary^Ci-galky^amino-Ci-galkyl, (aryl) ₂ -amino-C ₁ _galkyl, aryl-amino-carbonyl, aryl-Q-galkoxy, aryl-Ci-galkoxy-carbonyl-amino, heteroaryl, heteroaryl-Ci-galkyl, heteroaryl-amino, (heteroaryl) ₂ -amino,

heteroaryl-Ci-galkyl-amino, (heteroaryl-Ci-galky^Ci-galky^amino,

(heteroaryl-C ₁ _galkyl) ₂ -amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl,

(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl,

(heteroaryl-C ₁ _galkyl) ₂ -amino-C ₁ _galkyl, heterocyclyl, heterocyclyl-Ci-galkyl, heterocyclyl-amino-Ci-galkyl or heterocyclyl-oxy;

wherein each instance of Cs-^cycloalkyl is optionally substituted with one substituent

selected from R9; and,

wherein each instance of aryl is optionally substituted with one halogen substituent; and, R9 is Ci-galkyl, amino, Ci-galkyl-amino, (C ₁ _ ₈ alkyl) ₂ -amino, amino-Ci-galkyl,

Ci-galkyl-amino-Ci-galkyl, (C ₁ _galkyl) ₂ -amino-C ₁ _galkyl or aryl-Ci-galkyl-amino; and, wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , R _5c and R _5d substituted on a R ₁₍ JI, R _le i, Rin and R _lgl ring system is: Cs-^cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from pyrrolyl, thiazolyl, 1H- 1,2,3- triazolyl, lH-tetrazolyl, 2H-tetrazolyl, lH-imidazolyl or pyridinyl; and,

heterocyclyl selected in each instance, when present, from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 1,3-dioxolanyl, 2,5-dihydro- lH-pyrrolyl, 4,5-dihydro- lH-imidazolyl, 1 ,4,5,6-tetrahydropyrimidinyl, 1,2,3,6-tetrahydropyridinyl, tetrahydro-2H-pyranyl, indolinyl, 2,3- dihydrobenzo[d]oxazolyl, 3,4-dihydro-2H-benzo[b] [l,4]oxazinyl, 3,4- dihydroisoquinolin-(lH)-yl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4- tetrahydroquinoxalinyl, (6H)-pyrrolo[3,4-b] [l,4]oxazin-(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b] [l,4]oxazin-(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrolyl, (cis)- octahydrocyclopenta[c]pyrrolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- (lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b] [l,4]oxazinyl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- (2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9- tetrahydro- lH-carbazolyl, 1 ,2,3,4-tetrahydropyrazino[ 1 ,2-a]indolyl, 2,3-dihydro- 1H- pyrrolo[l,2-a]indolyl, l,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)- l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)- lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept- 5-enyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexanyl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexyl, (lR,5S,6s)-3-azabicyclo[3.1.0]hexanyl, (lR,5S)-3- azabicyclo[3.1.0]hexyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexyl, 3,6-diazabicyclo[3.1.0]hexanyl, (lS,5R,6R)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6R)-3-azabicyclo[3.2.0]heptanyl, (lS,5R,6S)-3- azabicyclo[3.2.0]heptyl, (lS,5R,6S)-3-azabicyclo[3.2.0]heptanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptyl, 5-azaspiro[2.4]heptanyl, 2,6- diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7- diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decyl, 2- azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl or 2,8-diazaspiro[4.5]decanyl.

The present description also relates to use of a compound of Formula (I) or a form thereof wherein R _5a , R _5b , R _5c and R _5d substituted on a R ₁₍ JI, R _le i, Rin and R _lgl ring system is: Cs-^cycloalkyl selected in each instance, when present, from cyclopropyl, cyclobutyl,

cyclopentyl, cyclohexyl or cycloheptyl;

aryl selected in each instance, when present, from phenyl;

heteroaryl selected in each instance, when present, from IH-pyrrol- l-yl, thiazol-2-yl, 1H-

1,2,3-triazol- l-yl, lH-tetrazol-5-yl, 2H-tetrazol-2-yl, lH-imidazol-l-yl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl; or,

heterocyclyl selected in each instance, when present, from azetidin- l-yl, tetrahydrofuran-2-yl, pyrrolidin-l-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin- l-yl, piperazin-2-yl, morpholin-4-yl, 1,4- diazepan- l-yl, l,3-dioxolan-2-yl, 2,5-dihydro-lH-pyrrol- l-yl, 4,5-dihydro- lH- imidazol-2-yl, 1 ,4,5,6-tetrahydropyrimidin-2-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, tetrahydro-2H-pyran-2-yl, tetrahydro-2H-pyran-4-yl, tetrahydro-2H-pyran-6-yl, indolinyl, 2,3-dihydrobenzo[d]oxazol-6-yl, 3,4-dihydro-2H-benzo[b][l,4]oxazin-4-yl, 3,4-dihydroisoquinolin-2(lH)-yl, 1,2,3,4-tetrahydroisoquinolin- l-yl, 1,2,3,4- tetrahydroquinoxalin- 1-yl, (6H)-pyrrolo[3,4-b] [ 1 ,4] oxazin-6(2H)-yl,

hexahydropyrrolo[3,4-b][l,4]oxazin-6(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4- b] [l,4]oxazin-4(4aH)-yl, hexahydro-lH-cyclopenta[c]pyrrol-2-yl, (cis)- octahydrocyclopenta[c]pyrrol-4-yl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-3a(lH)- yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,4S,6aS)- hexahydrocyclopenta[c]pyrrol-2(lH)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol- 2(lH)-yl, hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, 3,4-dihydro-2H-pyrido[3,2- b][l,4]oxazin-4-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-5(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-6(7H)-yl, 5,7- dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl, tetrahydro-lH-pyrrolo[3,4-b]pyridin- 6(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, (4aR,7aR)- hexahydro-lH-pyrrolo[3,4-b]pyridin-6(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridin- 6-yl, 2,3,4,9-tetrahydro-lH-carbazolyl, l,2,3,4-tetrahydropyrazino[l,2-a]indolyl, 2,3- dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, 1 ,3-dihydro-2H-isoindol-2-yl, octahydro-2H- isoindol-2-yl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-lH- isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4R,7aS)-octahydro-2H-isoindol-2-yl, (3aR,4S,7aS)-octahydro-2H-isoindol-2-yl, 2,5-diazabicyclo[2.2.1]hept-2-yl, 2,5-diazabicyclo[2.2.1]heptan-2-yl, 2- azabicyclo[2.2.1]hept-5-en-2-yl, 3-azabicyclo[3.1.0]hex-3-yl, 3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S,6s)-3-azabicyclo[3.1.0]hex-3-yl, (lR,5S,6s)-3- azabicyclo[3.1.0]hexan-3-yl, (lR,5S)-3-azabicyclo[3.1.0]hex-6-yl, (lR,5S)-3- azabicyclo[3.1.0]hexan-6-yl, 3,6-diazabicyclo[3.1.0]hex-3-yl, 3,6- diazabicyclo[3.1.0]hexan-3-yl, (lS,5R,6R)-3-azabicyclo[3.2.0]hept-3-yl, (1S,5R,6S)- 3-azabicyclo[3.2.0]hept-3-yl, (lS,5R)-3-azabicyclo[3.2.0]heptan-3-yl, 5- azaspiro[2.4]hept-5-yl, 5-azaspiro[2.4]heptan-5-yl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,5-diazaspiro[3.4]octan-2-yl, 2,6-diazaspiro[3.4]octan-6-yl, 2,7- diazaspiro[3.5]nonan-2-yl, 2,7-diazaspiro[4.4]nonan-2-yl, 2-azaspiro[4.5]dec-2-yl, 2- azaspiro[4.5]decan-2-yl, 2,8-diazaspiro[4.5]dec-2-yl or 2,8-diazaspiro[4.5]decan-2-yl.

The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R ₁₍₁ , Ri _e , Ri _f and R _lg is selected from the R ₁₍ JI, Ri _e i, Rin and R _lgl ring system, respectively, and R _5a , R _5b , R _5c and R _5d , when present, are selected from the group consisting of:

hydrogen, halogen, Ci-galkyl or hydroxyl-Ci-galkyl; and,

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof. The present description further relates to a compound of Formula (I) or a form thereof, wherein the ring system R ₁₍₁ , Ri _e , Ri _f and R _lg is selected from the R ₁₍ JI, Riei , Rin and R _lgl ring system, respectively, and R _5a , R ₅ b, R _5c and R ₅ d, when present, are selected from the group consisting of (where "Ring" in the table below indicates whether an R ₁₍ JI, R _le i, Rin or R _lgl ring system is selected; and, "— " indicates that one or more of Rs _a , Rs , R _5c or Rsa are not present):

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In one embodiment of the present description, the compound of Formula (I) or a form thereof is selected from the group consisting of:

15045440

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In one embodiment of the present description, the compound of Formula (I) or a form thereof (wherein compound number (#*) indicates that the salt form was isolated) is selected from the group consisting of:

Cpd Name

Ϊ ¹ 6-(lH-benzimidazol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydro pyridine-3- carboxylic acid

2 6-(2,3-dihydro-lH-indol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-di hydropyridine-3- carboxylic acid

3 ¹ 5-ethyl-4-hydroxy-2-oxo-6-[3-(pyrrolidin-l-ylmethyl)-lH-indo l-6-yl]-l,2- dihydropyridine-3-carboxylic acid

4 ¹ 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-lH-indol-6-yl)-4-hydroxy-2-oxo-l ,2- dihydropyridine-3-carboxylic acid

5 ¹ 6-[2-(aminomethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l, 2-dihydropyridine-

3-carboxylic acid

6 5-ethyl-4-hydroxy-6-(2-methyl-lH-benzimidazol-5-yl)-2-oxo-l, 2- dihydropyridine-3-carboxylic acid

7 ¹ 5-ethyl-6-(l, 2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid

8 ¹ 5-ethyl-4-hydroxy-6-(3-methyl- 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

9 5-cyclopropyl-4-hydroxy-6-(lH-indol-6-yl)-2-oxo-l,2-dihydrop yridine-3- carboxylic acid

10 ¹ 6-{3-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid

ll ¹ 5-ethyl-4-hydroxy-6-(l-methyl-l,2,3,4-tetrahydroquinoxalin-6 -yl)-2-oxo-l,2- dihydropyridine-3-carboxylic acid

12 ¹ 6-[l-(dimethylamino)-2,3,4,9-tetrahydro-lH-carbazol-7-yl]-5- ethyl-4-hydroxy-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid Cpd Name

13 6-(3,4-dihydro-2H- 1 ,4-benzoxazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

14 ¹ 6-{2-[(dimethylamino)methyl]-3-methyl-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

15 ¹ 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-3-methyl-lH-indol-6-yl)-4-hydrox y-

2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

16 ¹ 6-(3,4-dihydro-2H- 1 ,4-benzothiazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

17 ¹ 5-ethyl-6-(l, 2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid

18 ¹ 5-ethyl-4-hydroxy-6-(2-methyl- 1,2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-

2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

19 5-ethyl-4-hydroxy-6- [2-(2-hydroxyethyl)- 1 -methyl- lH-indol-5-yl] -2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

20 6-(3-cyano-lH-indol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydr opyridine-3- carboxylic acid

21 ¹ 5-ethyl-4-hydroxy-2-oxo-6-( 1 ,2,3,4-tetrahydroquinoxalin-6-yl)- 1 ,2- dihydropyridine-3-carboxylic acid

22 6-{2-[2-(dimethylamino)ethyl]-l-methyl-lH-indol-5-yl}-5-ethy l-4-hydroxy-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

23 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(pyrrolidin-l-yl)ethyl]-lH-indol-5-yl}-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

24 ¹ 6-[2-(2-aminoethyl)- 1 -methyl- lH-indol-5-yl] -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

25 ¹ 6-{2-[(dimethylamino)methyl]-3-(trifluoromethyl)-lH-indol-6- yl}-5-ethyl-4- hydroxy-2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

26 ¹ 5-ethyl-6-{2-[(ethylamino)methyl]-3-(trifluoromethyl)-lH-ind ol-6-yl}-4-hydroxy-

2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

27 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(methylamino)ethyl]-lH-indol-5-yl}-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid Cpd Name

28 ¹ 5-ethyl-6- { 2- [2- (ethylamino)ethyl] - 1 -methyl- 1 H-indol-5-yl } -4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

29 ¹ 6-{3-chloro-2-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

30 ¹ 6-{2-[(dimethylamino)methyl]-lH-indol-5-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid

31 ¹ 5-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-l-ylmethyl)-lH-indo l-5-yl]-l,2- di ydropyridine-3-carboxylic acid

32 ¹ 6-[2-(2-aminoethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l ,2-dihydropyridine-

3-carboxylic acid

33 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[(propylamino)methyl]-lH-indol-5-yl}-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

34 ¹ 6-{2-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

35 ¹ 5-ethyl-4-hydroxy-2-oxo-6-{2-[2-(pyrrolidin-l-yl)ethyl]-lH-i ndol-6-yl}-l,2- dihydropyridine-3-carboxylic acid

36 ¹ 6-{3-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

37 ammonium 6-{2-[(dimethylamino)methyl]-3-fluoro-lH-indol-6-yl}-5-ethyl -4- hydroxy-2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

38 ¹ 5-ethyl-6-{3-fluoro-2-[(methylamino)methyl]-lH-indol-6-yl}-4 -hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

39 ¹ 5-ethyl-4-hydroxy-6-[3-methyl-2-(N-methylglycyl)-lH-indol-6- yl]-2-oxo-l,2- dihydropyridine-3-carboxylic acid

40 ¹ 6-[2-(N,N-dimethylglycyl)-3-methyl-lH-indol-6-yl]-5-ethyl-4- hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

41 5-ethyl-6-(5-fluoro- lH-indol-6-yl)-4-hydroxy-2-oxo- l,2-dihydropyridine-3- carboxylic acid

42 ¹ 5-ethyl-4-hydroxy-6-{2-[l-(methylamino)ethyl]-lH-indol-6-yl} -2-oxo-l,2- dihydropyridine-3-carboxylic acid Cpd Name

43 ¹ 6- { 2- [ 1 - (dimethylamino)ethyl] - 1 H-indol-6-yl } -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

44 ¹ 4-hydroxy-6-[4-(2-hydroxyethyl)-2,3-dihydro-lH-indol-5-yl]-5 -methoxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

45 5-ethyl-6-(6-fluoro-l-methyl-lH-indol-5-yl)-4-hydroxy-2-oxo- l,2- dihydropyridine-3-carboxylic acid

46 5-ethyl-6-(6-fluoro- lH-indol-5-yl)-4-hydroxy-2-oxo- l,2-dihydropyridine-3- carboxylic acid

47 ¹ 5-ethyl-6-(6-fluoro-2,3-dihydro-lH-indol-5-yl)-4-hydroxy-2-o xo-l,2- dihydropyridine-3-carboxylic acid

48 ¹ 5-ethyl-6-(6-fluoro-l-methyl-2,3-dihydro-lH-indol-5-yl)-4-hy droxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

49 4-hydroxy-6-(lH-indol-7-yl)-5-methyl-2-oxo-l,2-dihydropyridi ne-3-carboxylic acid

50 5-ethyl-4-hydroxy-6-(lH-indol-7-yl)-2-oxo-l,2-dihydropyridin e-3-carboxylic acid

51 4-hydroxy-5-methyl-6-( 1 -methyl- 1 H-indol-7-yl)-2-oxo- 1 ,2-dihydropyridine-3- carboxylic acid

52 5-ethyl-4-hydroxy-6-(l-methyl-lH-indol-7-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid, and

53 ¹ 5-amino-4-hydroxy-6-(l-methyl-lH-indol-5-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid; wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In another embodiment of the present description, the compound or a form thereof is isolated as a salt. In another embodiment of the present description, a compound salt of Formula (I) or a form thereof selected from the group consisting of:

Cpd Name

I 6-(lH-benzimidazol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydro pyridine-3- carboxylic acid trifluoroacetate

3 5-ethyl-4-hydroxy-2-oxo-6-[3-(pyrrolidin-l-ylmethyl)-lH-indo l-6-yl]-l,2- dihydropyridine-3-carboxylic acid hydrochloride

4 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-lH-indol-6-yl)-4-hydroxy-2-oxo-l ,2- dihydropyridine-3-carboxylic acid hydrochloride

5 6-[2-(aminomethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l, 2-dihydropyridine- 3-carboxylic acid hydrochloride

7 5-ethyl-6-(l, 2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid hydrochloride

8 5-ethyl-4-hydroxy-6-(3-methyl- 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

10 6-{3-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

II 5-ethyl-4-hydroxy-6-(l-methyl-l,2,3,4-tetrahydroquinoxalin-6 -yl)-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

12 6-[l-(dimethylamino)-2,3,4,9-tetrahydro-lH-carbazol-7-yl]-5- ethyl-4-hydroxy-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

14 6-{2-[(dimethylamino)methyl]-3-methyl-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

15 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-3-methyl-lH-indol-6-yl)-4-hydrox y-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

16 6-(3,4-dihydro-2H- 1 ,4-benzothiazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

17 5-ethyl-6-(l, 2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid hydrochloride

18 5-ethyl-4-hydroxy-6-(2-methyl- 1,2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride Cpd Name

21 5-ethyl-4-hydroxy-2-oxo-6-( 1 ,2,3,4-tetrahydroquinoxalin-6-yl)- 1 ,2-dihydropyridine- 3-carboxylic acid hydrochloride

23 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(pyrrolidin-l-yl)ethyl]-lH-indol-5-yl}-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

24 6-[2-(2-aminoethyl)- 1 -methyl- lH-indol-5-yl] -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

25 6-{2-[(dimethylamino)methyl]-3-(trifluoromethyl)-lH-indol-6- yl}-5-ethyl-4- hydroxy-2-oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

26 5-ethyl-6-{2-[(ethylamino)methyl]-3-(trifluoromethyl)-lH-ind ol-6-yl}-4-hydroxy-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

27 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(methylamino)ethyl]-lH-indol-5-yl}-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

28 5-ethyl-6- { 2- [2- (ethylamino)ethyl] - 1 -methyl- 1 H-indol-5-yl } -4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

29 6-{3-chloro-2-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

30 6-{2-[(dimethylamino)methyl]-lH-indol-5-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

31 5-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-l-ylmethyl)-lH-indo l-5-yl]-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

32 6-[2-(2-aminoethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l ,2-dihydropyridine- 3-carboxylic acid hydrochloride

33 5-ethyl-4-hydroxy-6-{ l-methyl-2-[(propylamino)methyl]-lH-indol-5-yl}-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

34 6-{2-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

35 5-ethyl-4-hydroxy-2-oxo-6-{2-[2-(pyrrolidin-l-yl)ethyl]-lH-i ndol-6-yl}-l,2- dihydropyridine-3-carboxylic acid hydrochloride

36 6-{3-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride Cpd Name

38 5-ethyl-6-{3-fluoro-2-[(methylamino)methyl]-lH-indol-6-yl}-4 -hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

39 5-ethyl-4-hydroxy-6-[3-methyl-2-(N-methylglycyl)-lH-indol-6- yl]-2-oxo-l,2- di ydropyridine-3-carboxylic acid hydrochloride

40 6-[2-(N,N-dimethylglycyl)-3-methyl-lH-indol-6-yl]-5-ethyl-4- hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

42 5-ethyl-4-hydroxy-6-{2-[l-(methylamino)ethyl]-lH-indol-6-yl} -2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

43 6- { 2- [ 1 - (dimethylamino)ethyl] - 1 H-indol-6-yl } -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

44 4-hydroxy-6-[4-(2-hydroxyethyl)-2,3-dihydro-lH-indol-5-yl]-5 -methoxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

47 5-ethyl-6-(6-fluoro-2,3-dihydro-lH-indol-5-yl)-4-hydroxy-2-o xo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

48 5-ethyl-6-(6-fluoro-l-methyl-2,3-dihydro-lH-indol-5-yl)-4-hy droxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride, and

53 5-amino-4-hydroxy-6-(l-methyl-lH-indol-5-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid hydrochloride; wherein a form of the compound salt is selected from the group consisting of a prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In another embodiment, the present description includes a method of use for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound or a form thereof for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof (wherein compound number (#*) indicates that the salt form was isolated) to the subject, selected from the group consisting of:

Cpd Name

Ϊ ¹ 6-(lH-benzimidazol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydro pyridine-3- carboxylic acid

2 6-(2,3-dihydro-lH-indol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-di hydropyridine-3- carboxylic acid

3 ¹ 5-ethyl-4-hydroxy-2-oxo-6-[3-(pyrrolidin-l-ylmethyl)-lH-indo l-6-yl]-l,2- dihydropyridine-3-carboxylic acid

4 ¹ 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-lH-indol-6-yl)-4-hydroxy-2-oxo-l ,2- dihydropyridine-3-carboxylic acid

5 ¹ 6-[2-(aminomethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l, 2-dihydropyridine-3- carboxylic acid

6 5-ethyl-4-hydroxy-6-(2-methyl- lH-benzimidazol-5-yl)-2-oxo- 1 ,2-dihydropyridine-3- carboxylic acid

7 ¹ 5-ethyl-6-(l, 2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid

8 ¹ 5-ethyl-4-hydroxy-6-(3-methyl- 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

9 5-cyclopropyl-4-hydroxy-6-(lH-indol-6-yl)-2-oxo-l,2-dihydrop yridine-3-carboxylic acid

10 ¹ 6-{3-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid

ll ¹ 5-ethyl-4-hydroxy-6-(l-methyl-l,2,3,4-tetrahydroquinoxalin-6 -yl)-2-oxo-l,2- dihydropyridine-3-carboxylic acid

12 ¹ 6-[l-(dimethylamino)-2,3,4,9-tetrahydro-lH-carbazol-7-yl]-5- ethyl-4-hydroxy-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

13 6-(3,4-dihydro-2H- 1 ,4-benzoxazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

14 ¹ 6-{2-[(dimethylamino)methyl]-3-methyl-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid Cpd Name

15 ¹ 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-3-methyl-lH-indol-6-yl)-4-hydrox y-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

16 ¹ 6-(3,4-dihydro-2H- 1 ,4-benzothiazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- di ydropyridine-3-carboxylic acid

17 ¹ 5-ethyl-6-(l, 2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid

18 ¹ 5-ethyl-4-hydroxy-6-(2-methyl- 1,2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

19 5-ethyl-4-hydroxy-6- [2-(2-hydroxyethyl)- 1 -methyl- lH-indol-5-yl] -2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

20 6-(3-cyano-lH-indol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydr opyridine-3- carboxylic acid

21 ¹ 5-ethyl-4-hydroxy-2-oxo-6-( 1 ,2,3,4-tetrahydroquinoxalin-6-yl)- 1 ,2-dihydropyridine- 3-carboxylic acid

22 6-{2-[2-(dimethylamino)ethyl]-l-methyl-lH-indol-5-yl}-5-ethy l-4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

23 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(pyrrolidin-l-yl)ethyl]-lH-indol-5-yl}-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid

24 ¹ 6-[2-(2-aminoethyl)- 1 -methyl- lH-indol-5-yl] -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

25 ¹ 6-{2-[(dimethylamino)methyl]-3-(trifluoromethyl)-lH-indol-6- yl}-5-ethyl-4- hydroxy-2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

26 ¹ 5-ethyl-6-{2-[(ethylamino)methyl]-3-(trifluoromethyl)-lH-ind ol-6-yl}-4-hydroxy-2- oxo- 1 ,2-dihydropyridine-3-carboxylic acid

27 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(methylamino)ethyl]-lH-indol-5-yl}-2-oxo-l,2- dihydropyridine-3-carboxylic acid

28 ¹ 5-ethyl-6- { 2- [2- (ethylamino)ethyl] - 1 -methyl- 1 H-indol-5-yl } -4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

29 ¹ 6-{3-chloro-2-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo-

1 ,2-dihydropyridine-3-carboxylic acid Cpd Name

30 ¹ 6-{2-[(dimethylamino)methyl]-lH-indol-5-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- di ydropyridine-3-carboxylic acid

31 ¹ 5-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-l-ylmethyl)-lH-indo l-5-yl]-l,2- di ydropyridine-3-carboxylic acid

32 ¹ 6-[2-(2-aminoethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l ,2-dihydropyridine-3- carboxylic acid

33 ¹ 5-ethyl-4-hydroxy-6-{ l-methyl-2-[(propylamino)methyl]-lH-indol-5-yl}-2-oxo-l,2- di ydropyridine-3-carboxylic acid

34 ¹ 6-{2-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

35 ¹ 5-ethyl-4-hydroxy-2-oxo-6-{2-[2-(pyrrolidin-l-yl)ethyl]-lH-i ndol-6-yl}-l,2- dihydropyridine-3-carboxylic acid

36 ¹ 6-{3-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

37 ammonium 6-{2-[(dimethylamino)methyl]-3-fluoro-lH-indol-6-yl}-5-ethyl -4- hydroxy-2-oxo- 1 ,2-dihydropyridine-3-carboxylic acid

38 ¹ 5-ethyl-6-{3-fluoro-2-[(methylamino)methyl]-lH-indol-6-yl}-4 -hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

39 ¹ 5-ethyl-4-hydroxy-6-[3-methyl-2-(N-methylglycyl)-lH-indol-6- yl]-2-oxo-l,2- dihydropyridine-3-carboxylic acid

40 ¹ 6-[2-(N,N-dimethylglycyl)-3-methyl-lH-indol-6-yl]-5-ethyl-4- hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

41 5-ethyl-6-(5-fluoro- lH-indol-6-yl)-4-hydroxy-2-oxo- l,2-dihydropyridine-3- carboxylic acid

42 ¹ 5-ethyl-4-hydroxy-6-{2-[l-(methylamino)ethyl]-lH-indol-6-yl} -2-oxo-l,2- dihydropyridine-3-carboxylic acid

43 ¹ 6- { 2- [ 1 - (dimethylamino)ethyl] - 1 H-indol-6-yl } -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid

44 ¹ 4-hydroxy-6-[4-(2-hydroxyethyl)-2,3-dihydro-lH-indol-5-yl]-5 -methoxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid Cpd Name

45 5-ethyl-6-(6-fluoro-l-methyl-lH-indol-5-yl)-4-hydroxy-2-oxo- l,2-dihydropyridine- 3-carboxylic acid

46 5-ethyl-6-(6-fluoro- lH-indol-5-yl)-4-hydroxy-2-oxo- l,2-dihydropyridine-3- carboxylic acid

47 ¹ 5-ethyl-6-(6-fluoro-2,3-dihydro-lH-indol-5-yl)-4-hydroxy-2-o xo-l,2- dihydropyridine-3-carboxylic acid

48 ¹ 5-ethyl-6-(6-fluoro-l-methyl-2,3-dihydro-lH-indol-5-yl)-4-hy droxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

49 4-hydroxy-6-(lH-indol-7-yl)-5-methyl-2 -oxo- 1 ,2-dihydropyridine-3-carboxylic acid

50 5-ethyl-4-hydroxy-6-(lH-indol-7-yl)-2-oxo-l,2-dihydropyridin e-3-carboxylic acid

51 4-hydroxy-5-methyl-6-( 1 -methyl- 1 H-indol-7-yl)-2-oxo- 1 ,2-dihydropyridine-3- carboxylic acid

52 5-ethyl-4-hydroxy-6-(l-methyl-lH-indol-7-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid, and

53 ¹ 5-amino-4-hydroxy-6-(l-methyl-lH-indol-5-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid; wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

Another embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound salt or a form thereof for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound salt of Formula (I) or a form thereof to the subject, selected from the group consisting of:

Cpd Name

1 6-(lH-benzimidazol-6-yl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydro pyridine-3- carboxylic acid trifluoroacetate

3 5-ethyl-4-hydroxy-2-oxo-6-[3-(pyrrolidin-l-ylmethyl)-lH-indo l-6-yl]-l,2- dihydropyridine-3-carboxylic acid hydrochloride Cpd Name

4 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-lH-indol-6-yl)-4-hydroxy-2-oxo-l ,2- di ydropyridine-3-carboxylic acid hydrochloride

5 6-[2-(aminomethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l, 2-dihydropyridine- 3-carboxylic acid hydrochloride

7 5-ethyl-6-(l, 2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid hydrochloride

8 5-ethyl-4-hydroxy-6-(3-methyl- 1,2,3,4,5, 6-hexahydroazepino[4,5-b]indol-8-yl)-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

10 6-{3-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

11 5-ethyl-4-hydroxy-6-(l-methyl-l,2,3,4-tetrahydroquinoxalin-6 -yl)-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

12 6-[l-(dimethylamino)-2,3,4,9-tetrahydro-lH-carbazol-7-yl]-5- ethyl-4-hydroxy-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

14 6-{2-[(dimethylamino)methyl]-3-methyl-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

15 5-ethyl-6-(2-{ [ethyl(methyl)amino]methyl}-3-methyl-lH-indol-6-yl)-4-hydrox y-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

16 6-(3,4-dihydro-2H- 1 ,4-benzothiazin-6-yl)-5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

17 5-ethyl-6-(l, 2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-4-hydroxy-2-oxo- 1,2- dihydropyridine-3-carboxylic acid hydrochloride

18 5-ethyl-4-hydroxy-6-(2-methyl- 1,2,3,4,5, 10-hexahydroazepino[3,4-b]indol-8-yl)-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

21 5-ethyl-4-hydroxy-2-oxo-6-( 1 ,2,3,4-tetrahydroquinoxalin-6-yl)- 1 ,2-dihydropyridine- 3-carboxylic acid hydrochloride

23 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(pyrrolidin-l-yl)ethyl]-lH-indol-5-yl}-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

24 6-[2-(2-aminoethyl)- 1 -methyl- lH-indol-5-yl] -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride Cpd Name

25 6-{2-[(dimethylamino)methyl]-3-(trifluoromethyl)-lH-indol-6- yl}-5-ethyl-4- hydroxy-2-oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

26 5-ethyl-6-{2-[(ethylamino)methyl]-3-(trifluoromethyl)-lH-ind ol-6-yl}-4-hydroxy-2- oxo-l,2-dihydropyridine-3-carboxylic acid hydrochloride

27 5-ethyl-4-hydroxy-6-{ l-methyl-2-[2-(methylamino)ethyl]-lH-indol-5-yl}-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

28 5-ethyl-6- { 2- [2- (ethylamino)ethyl] - 1 -methyl- 1 H-indol-5-yl } -4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

29 6-{3-chloro-2-[(dimethylamino)methyl]-lH-indol-6-yl}-5-ethyl -4-hydroxy-2-oxo- l,2-dihydropyridine-3-carboxylic acid hydrochloride

30 6-{2-[(dimethylamino)methyl]-lH-indol-5-yl}-5-ethyl-4-hydrox y-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

31 5-ethyl-4-hydroxy-2-oxo-6-[2-(pyrrolidin-l-ylmethyl)-lH-indo l-5-yl]-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

32 6-[2-(2-aminoethyl)-lH-indol-6-yl]-5-ethyl-4-hydroxy-2-oxo-l ,2-dihydropyridine- 3-carboxylic acid hydrochloride

33 5-ethyl-4-hydroxy-6-{ l-methyl-2-[(propylamino)methyl]-lH-indol-5-yl}-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

34 6-{2-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

35 5-ethyl-4-hydroxy-2-oxo-6-{2-[2-(pyrrolidin-l-yl)ethyl]-lH-i ndol-6-yl}-l,2- dihydropyridine-3-carboxylic acid hydrochloride

36 6-{3-[2-(dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hydro xy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

38 5-ethyl-6-{3-fluoro-2-[(methylamino)methyl]-lH-indol-6-yl}-4 -hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate

39 5-ethyl-4-hydroxy-6-[3-methyl-2-(N-methylglycyl)-lH-indol-6- yl]-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

40 6-[2-(N,N-dimethylglycyl)-3-methyl-lH-indol-6-yl]-5-ethyl-4- hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid trifluoroacetate Cpd Name

42 5-ethyl-4-hydroxy-6-{2-[l-(methylamino)ethyl]-lH-indol-6-yl} -2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

43 6- { 2- [ 1 - (dimethylamino)ethyl] - 1 H-indol-6-yl } -5-ethyl-4-hydroxy-2-oxo- 1 ,2- dihydropyridine-3-carboxylic acid hydrochloride

44 4-hydroxy-6-[4-(2-hydroxyethyl)-2,3-dihydro-lH-indol-5-yl]-5 -methoxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

47 5-ethyl-6-(6-fluoro-2,3-dihydro-lH-indol-5-yl)-4-hydroxy-2-o xo-l,2- dihydropyridine-3-carboxylic acid hydrochloride

48 5-ethyl-6-(6-fluoro-l-methyl-2,3-dihydro-lH-indol-5-yl)-4-hy droxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid hydrochloride, and

53 5-amino-4-hydroxy-6-(l-methyl-lH-indol-5-yl)-2-oxo-l,2-dihyd ropyridine-3- carboxylic acid hydrochloride; wherein a form of the compound salt is selected from the group consisting of a prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In another embodiment, the present description includes a method of use for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

In another embodiment, the present description includes a method of use for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound salt of Formula (I) or a form thereof to the subject.

In another embodiment of the present description, the compound salt or a form thereof is isolated for use.

Chemical Definitions The chemical terms used above and throughout the description herein, unless specifically defined otherwise, shall be understood by one of ordinary skill in the art to have the following indicated meanings. As used herein, the term "Ci-ioalkyl" generally refers to saturated hydrocarbon radicals having from one to ten carbon atoms in a straight or branched chain configuration, including, without limitation, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl and the like. In some embodiments, Ci-ioalkyl includes Ci-galkyl, Ci_ ₆ alkyl, C ₁ _ ₄ alkyl and the like. A Ci-ioalkyl radical may be optionally substituted where allowed by available valences.

As used herein, the term "C ₂ -galkenyl" generally refers to partially unsaturated hydrocarbon radicals having from two to eight carbon atoms in a straight or branched chain configuration and one or more carbon-carbon double bonds therein, including, without limitation, ethenyl, allyl, propenyl and the like. In some embodiments, C ₂ -galkenyl includes C ₂ - ₆ alkenyl, C ₂ - ₄ alkenyl and the like. A C ₂ -galkenyl radical may be optionally substituted where allowed by available valences.

As used herein, the term "C ₂ - ₈ alkynyl" generally refers to partially unsaturated hydrocarbon radicals having from two to eight carbon atoms in a straight or branched chain configuration and one or more carbon-carbon triple bonds therein, including, without limitation, ethynyl, propynyl and the like. In some embodiments, C ₂ -galkynyl includes C ₂ - ₆ alkynyl, C ₂ - ₄ alkynyl and the like. A C ₂ - ₈ alkynyl radical may be optionally substituted where allowed by available valences.

As used herein, the term "Ci-salkoxy" generally refers to saturated hydrocarbon radicals having from one to eight carbon atoms in a straight or branched chain configuration of the formula: -O-Ci-galkyl, including, without limitation, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy and the like. In some embodiments, Ci-salkoxy includes Ci^alkoxy, Ci_ ₄ alkoxy and the like. A Ci-salkoxy radical may be optionally substituted where allowed by available valences.

As used herein, the term "C ₃ _i ₄ cycloalkyl" generally refers to a saturated monocyclic, bicyclic or polycyclic hydrocarbon radical, including, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, lH-indanyl, indenyl, tetrahydro-naphthalenyl and the like. In some embodiments, C ₃ _ ₁₄ cycloalkyl includes C ₃ _gcycloalkyl, Cs-gcycloalkyl, C ₃ _iocycloalkyl and the like. A C3_ ₁₄ cycloalkyl radical may be optionally substituted where allowed by available valences.

As used herein, the term "aryl" generally refers to a monocyclic, bicyclic or polycyclic aromatic carbon atom ring structure radical, including, without limitation, phenyl, naphthyl, anthracenyl, fluorenyl, azulenyl, phenanthrenyl and the like. An aryl radical may be optionally substituted where allowed by available valences.

As used herein, the term "heteroaryl" generally refers to a monocyclic, bicyclic or polycyclic aromatic carbon atom ring structure radical in which one or more carbon atom ring members have been replaced, where allowed by structural stability, with one or more heteroatoms, such as an O, S or N atom, including, without limitation, furanyl, thienyl (also referred to as thiophenyl), pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolyl, indazolyl, indolizinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, 9H-purinyl, quinoxalinyl, isoindolyl, quinolinyl, isoquinolinyl, quinazolinyl, acridinyl and the like. A heteroaryl radical may be optionally substituted on a carbon or nitrogen atom ring member where allowed by available valences.

As used herein, the term "heterocyclyl" generally refers to a saturated or partially unsaturated monocyclic, bicyclic or polycyclic carbon atom ring structure radical in which one or more carbon atom ring members have been replaced, where allowed by structural stability, with a heteroatom, such as an O, S or N atom, including, without limitation, oxiranyl, oxetanyl, azetidinyl, dihydrofuranyl, tetrahydrofuranyl, dihydrothienyl,

tetrahydrothienyl, pyrrolinyl, pyrrolidinyl, dihydropyrazolyl, pyrazolinyl, pyrazolidinyl, 4,5- dihydro-lH-imidazolyl, imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl, isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, triazolinyl, triazolidinyl, oxadiazolinyl, oxadiazolidinyl, thiadiazolinyl, thiadiazolidinyl, tetrazolinyl, tetrazolidinyl, dihydro-2H-pyranyl, dihydro-pyridinyl, tetrahydro-pyridinyl, 1,2,3,6- tetrahydropyridinyl, hexahydro-pyridinyl, dihydro-pyrimidinyl, tetrahydro-pyrimidinyl, 1,4,5,6-tetrahydropyrimidinyl, dihydro-pyrazinyl, tetrahydro-pyrazinyl, dihydro-pyridazinyl, tetrahydro-pyridazinyl, piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl,

dihydro-triazinyl, tetrahydro-triazinyl, hexahydro-triazinyl, 1,4-diazepanyl, dihydro-indolyl, indolinyl, tetrahydro-indolyl, dihydro-indazolyl, tetrahydro-indazolyl, dihydro-isoindolyl, dihydro-benzofuranyl, tetrahydro-benzofuranyl, dihydro-benzothienyl,

tetrahydro-benzothienyl, dihydro-benzimidazolyl, tetrahydro-benzimidazolyl,

dihydro-benzooxazolyl, 2,3-dihydrobenzo[d]oxazolyl, tetrahydro-benzooxazolyl,

dihydro-benzooxazinyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, tetrahydro-benzooxazinyl, benzo[l,3]dioxolyl, benzo[l,4]dioxanyl, dihydro-purinyl, tetrahydro-purinyl, dihydro-quinolinyl, tetrahydro-quinolinyl, 1 ,2,3,4-tetrahydroquinolinyl,

dihydro-isoquinolinyl, 3,4-dihydroisoquinolin-(lH)-yl, tetrahydro-isoquinolinyl, 1,2,3,4- tetrahydroisoquinolinyl, dihydro-quinazolinyl, tetrahydro-quinazolinyl, dihydro-quinoxalinyl, tetrahydro-quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dioxolanyl, 2,5-dihydro-lH- pyrrolyl, 4,5-dihydro-lH-imidazolyl, tetrahydro-2H-pyranyl, hexahydropyrrolo[3,4- b][l,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4-b][l,4]oxazin-(4aH)-yl, 3,4-dihydro- 2H-pyrido[3,2-b][l,4]oxazinyl, (cis)-octahydrocyclopenta[c]pyrrolyl, hexahydropyrrolo[3,4- b]pyrrol-(lH)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(lH)-yl, (3aR,6aS)- hexahydropyrrolo[3,4-c]pyrrol-(lH)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7-dihydro-6H- pyrrolo[3,4-b]pyridinyl, tetrahydro-lH-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl, hexahydro- lH-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro-lH-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9-tetrahydro-lH-carbazolyl, 1,2,3,4- tetrahydropyrazino[ 1 ,2-a]indolyl, 2,3-dihydro- lH-pyrrolo[ 1 ,2-a]indolyl, (3aR,6aR)- hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(lH)-yl, (3aR,5r,6aS)- hexahydrocyclopenta[c]pyrrol-( lH)-yl, 1 ,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)-l,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-lH-isoindol- (3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)- octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5- diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]hept-5-enyl, 3-azabicyclo[3.1.0]hexanyl, 3,6- diazabicyclo[3.1.0]hexanyl, (lR,5S)-3-azabicyclo[3.1.0]hexanyl, (lS,5R)-3- azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,5- diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2,7- diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl and the like. A heterocyclyl radical may be optionally substituted on a carbon or nitrogen atom ring member where allowed by available valences.

As used herein, the term "C ₂ - ₈ alkenyl-amino" refers to a radical of the formula:

-NH-C ₂ - ₈ alkenyl.

As used herein, the term "(C ₂ - ₈ alkenyl) ₂ -amino" refers to a radical of the formula: -N(C ₂ _ ₈ alkenyl) ₂ .

As used herein, the term refers to a radical of the formula: -Ci-salkyl-NH-C^alkenyl. As used herein, the term ' C ₂ - ₈ alkenyl) ₂ -amino-C ₁ _ ₈ alkyr refers to a radical of the formula: -C ₁ _ ₈ alkyl-N(C ₂ - ₈ alkenyl) ₂ .

As used herein, the term "Ci-salkoxy-Ci-salkyl" refers to a radical of the formula: -Ci-galkyl-O-Ci-galkyl.

As used herein, the term "Ci-galkoxy-Ci-galkyl-amino" refers to a radical of the formula: -O-Ci.galkyl-NH-C^alkyl-O-C^alkyl.

As used herein, the term "(C ₁ _galkoxy-C ₁ _galkyl) ₂ -amino" refers to a radical of the formula: -N(C ₁ _galkyl-0-C ₁ -galkyl) ₂ .

As used herein, the term "Ci-galkoxy-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci.galkyl-NH-C^alkyl-O-Ci.galkyl.

As used herein, the term "(C ₁ _galkoxy-C ₁ -galkyl) ₂ -amino-C ₁ -galkyl" refers to a radical of the formula: -C ₁ -galkyl-N(C ₁ - ₈ alkyl-0-C ₁ -galkyl) ₂ .

As used herein, the term "(Ci-galkoxy-Ci-galky^Ci-galky^-amino" refers to a radical of the formula: -NK^galkylX^galkyl-O-Ci.galkyl)].

As used herein, the term "(Ci-galkoxy-Ci-galky^Ci-galky^-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NfCCi-galky CCi-galkyl-O-Ci-galkyl)].

As used herein, the term "Ci-galkoxy-carbonyl" refers to a radical of the formula: -C(0)-0-Ci_ ₈ alkyl.

As used herein, the term "Ci-galkyl-amino" refers to a radical of the formula:

-NH-Ci-galkyl.

As used herein, the term "(C ₁ _galkyl) ₂ -amino" refers to a radical of the formula:

-N(C ₁ . ₈ alkyl) ₂ .

As used herein, the term "Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-Ci-galkyl.

As used herein, the term "Ci-ioalkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci.galkyl-NH-C oalkyl.

As used herein, the term "(C ₁ _ ₁ oalkyl) ₂ -amino-C ₁ -galkyl" refers to a radical of the formula: -C ₁ _galkyl-N(C ₁ _ ₁ oalkyl) ₂ .

As used herein, the term "Ci-galkyl-amino-Ci-galkyl-amino" refers to a radical of the formula: -NH-Ci.galkyl-NH-Ci.galkyl.

As used herein, the term "(C ₁ -galkyl) ₂ -amino-C ₁ _galkyl-amino" refers to a radical of the formula: -NH-C ₁ - ₈ alkyl-N(C ₁ -galkyl) ₂ . As used herein, the term "Ci-galkyl-amino-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -C _1-8 alkyl-NH-C _1-8 alkyl-NH-C _1-8 alkyl.

As used herein, the term "(Ci-salky^i-amino-Ci-salkyl-amino-Ci-salkyl" refers to a radical of the formula: -C _1-8 alkyl-NH-C _1-8 alkyl-N(C _1-8 alkyl) ₂ .

As used herein, the term "(Ci-salkyl-amino-Ci-salky^Ci-salky^amino" refers to a radical of the formula: -NKC^alkylXCi.galkyl-NH-C^alkyl)].

As used herein, the term "[(Ci-galky^i-amino-Ci-galky^Ci-galky^amino" refers to a radical of the formula: -N{ (Ci-8alkyl)[Ci- ₈ alkyl-N(Ci-8alkyl) ₂ ] } .

As used herein, the term "(Ci-galkyl-amino-Ci-galky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci- ₈ alkyl-N[(Ci- ₈ alkyl)(Ci- ₈ alkyl-NH-Ci- ₈ alkyl)] .

As used herein, the term "[(C _1-8 alkyl) ₂ -aiidno-C _1-8 alkyl,C _1-8 alkyl]amino-C _1-8 alky ' refers to a radical of the formula: -C _1-8 alkyl-N{ (C _1-8 alkyl)[C _1-8 alkyl-N(C _1-8 alkyl) ₂ ] }.

As used herein, the term "(C ₁ _ ₈ alkyl-amino-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl" refers to a radical of the formula: -C ₁ _ ₈ alkyl-N(C ₁ _ ₈ alkyl-NH-C ₁ _ ₈ alkyl) ₂ .

As used herein, the term "Ci-salkyl-amino-carbonyl" refers to a radical of the formula:

-C(0)-NH-C _1-8 alkyl.

As used herein, the term "(C ₁ _galkyl) ₂ -amino-carbonyl" refers to a radical of the formula: -C(0)-N(C ₁ _ ₈ alkyl) ₂ .

As used herein, the term "C^alkyl-amino-C^alkyl-carbonyr refers to a radical of the formula: -C(0)-C ₁ - ₈ alkyl-NH-C ₁ _ ₈ alkyl.

As used herein, the term "(C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl-carbonyl" refers to a radical of the formula: -C(0)-C ₁ _ ₈ alkyl-N(C ₁ _ ₈ alkyl) ₂ .

As used herein, the term "Ci-salkyl-carbonyl" refers to a radical of the formula:

-C(0)-Ci- ₈ alkyl.

As used herein, the term "Ci-salkyl-carbonyl-amino" refers to a radical of the formula:

-NH-C(0)-Ci_ ₈ alkyl.

As used herein, the term "(Ci-salkyl-carbony^Ci-salky^amino-Ci-salkyl" refers to a radical of the formula: -C ₁ - ₈ alkyl-N[(C ₁ _ ₈ alkyl)(-C(0)-C ₁ - ₈ alkyl)].

As used herein, the term "Ci-salkyl-thio" refers to a radical of the formula:

-S-Ci_ ₈ alkyl.

As used herein, the term "C^salkynyl-Ci-salkyl" refers to a radical of the formula: -Ci-salkyl-C^salkynyl. As used herein, the term "C ₂ _galkynyl- amino" refers to a radical of the formula:

-NH-C ₂ _ ₈ alkynyl.

As used herein, the term "(C ₂ - ₈ alkynyl) ₂ -amino" refers to a radical of the formula: -N(C ₂ -8alkynyl) ₂ .

As used herein, the term refers to a radical of the formula: -C ₁ _ ₈ alkyl-NH-C ₂ - ₈ alkynyl.

As used herein, the term "(C ₂ - ₈ alkynyl) ₂ -amino-C ₁ - ₈ alkyl" refers to a radical of the formula: -C ₁ _8alkyl-N(C ₂ -8alkynyl) ₂ .

As used herein, the term "amino" refers to a radical of the formula: -NH ₂ .

As used herein, the term "amino-Ci-galkyl" refers to a radical of the formula:

-Ci. ₈ alkyl-NH ₂ .

As used herein, the term "amino-Ci-galkyl-amino" refers to a radical of the formula: -NH-C ₁ _ ₈ alkyl-NH ₂ .

As used herein, the term "(amino-C ₁ _galkyl) ₂ -amino" refers to a radical of the formula: -N(C ₁ _ ₈ alkyl-NH ₂ ) ₂ .

As used herein, the term "(amino-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ - ₈ alkyl" refers to a radical of the formula: -C ₁ _ ₈ alkyl-N(C ₁ _ ₈ alkyl-NH ₂ ) ₂ .

As used herein, the term "amino-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -C ₁ - ₈ alkyl-NH-C ₁ - ₈ alkyl-NH ₂ .

As used herein, the term "(amino-^galky^Ci-galky^amino" refers to a radical of the formula: -N[(C ₁ _ ₈ alkyl)(C ₁ _ ₈ alkyl-NH ₂ )] .

As used herein, the term "(amino-Ci-galky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -C ₁ - ₈ alkyl-N[(C ₁ - ₈ alkyl)(C ₁ - ₈ alkyl-NH ₂ )].

As used herein, the term "amino-carbonyl" refers to a radical of the formula:

-C(0)-NH ₂ .

As used herein, the term "aryl-Ci-galkoxy" refers to a radical of the formula:

-O-Ci-galkyl-aryl.

As used herein, the term "aryl-^galkoxy-carbonyl-amino" refers to a radical of the formula: -NH-C(0)-0-C ₁ _ ₈ alkyl-aryl.

As used herein, the term "aryl-Ci-galkyl" refers to a radical of the formula:

-Ci-galkyl-aryl.

As used herein, the term refers to a radical of the formula: -NH-Ci-galkyl-aryl. As used herein, the term "(aryl-C ₁ _ ₈ alkyl) ₂ -amino" refers to a radical of the formula: -NtCd-galkyl-aryDJ.

As used herein, the term "aryl-^galkyl-amino-Ci-galkyl" refers to a radical of the formula: -^galkyl-NH-Ci-galkyl-aryl.

As used herein, the term "(aryl-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl" refers to a radical of the formula: -C ₁ _ ₈ alkyl-N[(C ₁ _galkyl-aryl) ₂ ].

As used herein, the term refers to a radical of the formula: -N[(Ci_ ₈ alkyl)(aryl)] .

As used herein, the term "(ary^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci. ₈ alkyl-N[(Ci- ₈ alkyl)(aryl)].

As used herein, the term refers to a radical of the formula: -N[(Ci- ₈ alkyl)(Ci- ₈ alkyl-aryl)] .

As used herein, the term "(aryl-Ci-galky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci- ₈ alkyl-N[(Ci- ₈ alkyl)(Ci- ₈ alkyl-aryl)].

As used herein, the term "aryl-amino" refers to a radical of the formula: -NH-aryl.

As used herein, the term "(aryl) ₂ -amino" refers to a radical of the formula: -N[(aryl) ₂ ].

As used herein, the term "aryl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-aryl.

As used herein, the term "(aryl) ₂ -amino-C ₁ _galkyl" refers to a radical of the formula: -Ci. ₈ alkyl-N[(aryl) ₂ ].

As used herein, the term "aryl-amino-carbonyl" refers to a radical of the formula: -C(0)-NH-aryl.

As used herein, the term "azido" refers to a radical of the formula: -N=N ⁺ =N ^" .

As used herein, the term "carboxyl" refers to a radical of the formula: -COOH, -C(0)OH or -C0 ₂ H.

As used herein, the term "(carboxyl-Ci-galky^Ci-galky^amino-carbonyl-amino" refers to a radical of the formula: -NH-C(0)-N[(C ₁ _galkyl)(C ₁ -galkyl-C0 ₂ H)].

As used herein, the term "Cs-wcycloalkyl-Ci-galkoxy" refers to a radical of the formula:

As used herein, the term refers to a radical of the formula:

As used herein, the term "Cs-^cycloalkyl-amino" refers to a radical of the formula: -NH-C _3-14 cycloalkyl. As used herein, the term "Cs- _H cycloalkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-Cs-wcycloalkyl.

As used herein, the term "(Cs- _M cycloalkyl amino-Ci-galkyl" refers to a radical of the formula: -^galkyl-N[(C ₃ -i ₄ cycloalkyl) ₂ ] .

As used herein, the term "Cs- _H cycloalkyl-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-Ci-galkyl-Cs- _H cycloalkyl.

As used herein, the term "(Cs- _M cycloalkyl-Ci-galkyl amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-N ^galkyl-Cs-wcycloalkyl)^.

As used herein, the term "(Cs- _H cycloalky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-N Ci-galkylXCs- _H cycloalkyl)].

As used herein, the term "(Cs-wcycloalkyl-Ci-galky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NfiCi-galky^iCi-galkyl-Cs-^cycloalkyl)].

As used herein, the term "C ₃ _i ₄ cycloalkyl-oxy" refers to a radical of the formula: -O-Cs-ncycloalkyl.

As used herein, the term "formyl" refers to a radical of the formula: -C(0)-H.

As used herein, the term "formyl-Ci-galkyl" refers to a radical of the formula:

-Ci_ ₈ alkyl-C(0)-H.

As used herein, the term "halo" or "halogen" generally refers to a halogen atom radical, including fluoro, chloro, bromo and iodo.

As used herein, the term "halo-Ci-galkoxy" refers to a radical of the formula:

-O-Ci-galkyl-halo, wherein Ci_galkyl may be partially or completely substituted where allowed by available valences with one or more halogen atoms. In some embodiments, halo-Ci-galkoxy includes halo-C i^alkoxy, halo-Ci^alkoxy and the like.

As used herein, the term "halo-Ci-galkyl" refers to a radical of the formula:

-Ci-galkyl-halo, wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more halogen atoms. In some embodiments, halo-Ci-galkyl includes halo-Ci_ ₆ alkyl, halo-C i^alkyl and the like.

As used herein, the term "halo-Ci-galkyl-amino" refers to a radical of the formula: -NH-Ci-galkyl-halo.

As used herein, the term "(halo-Ci-galkyl^-amino" refers to a radical of the formula:

-N(Ci-galkyl-halo) ₂ .

As used herein, the term "halo-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -NH-Ci_galkyl-halo. As used herein, the term "(halo-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _ ₈ alkyl" refers to a radical of the formula: -C ₁ _ ₈ alkyl-N(C ₁ _galkyl-halo) ₂ .

As used herein, the term "heteroaryl-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-heteroaryl.

As used herein, the term "heteroaryl- amino" refers to a radical of the formula:

-NH-heteroaryl.

As used herein, the term "(heteroaryl) ₂ -amino" refers to a radical of the formula: -N[(heteroaryl) ₂ ].

As used herein, the term "heteroaryl-Ci-galkyl-amino" refers to a radical of the formula: -NH-Ci-galkyl-heteroaryl.

As used herein, the term "(heteroaryl-C ₁ _ ₈ alkyl) ₂ -amino" refers to a radical of the formula: -N[(C ₁ _ ₈ alkyl-heteroaryl) ₂ ] .

As used herein, the term "heteroaryl-Ci-galkyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-Ci-galkyl-heteroaryl.

As used herein, the term "(heteroaryl-C ₁ -galkyl) ₂ -amino-C ₁ _galkyl" refers to a radical of the formula: -C ₁ _galkyl-N[(C ₁ _galkyl-heteroaryl) ₂ ].

As used herein, the term "(heteroaryl-Ci-galky^Ci-galky^amino" refers to a radical of the formula: -N Ci-galkylXCi-galkyl-heteroaryl)].

As used herein, the term "(heteroary^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci- ₈ alkyl-N[(Ci- ₈ alkyl)(heteroaryl)].

As used herein, the term "(heteroaryl-Ci-galky^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-N Ci-galkylXCi-galkyl -heteroaryl)].

As used herein, the term "heterocyclyl-Ci-galkoxy" refers to a radical of the formula: -O-Ci-galkyl-heterocyclyl.

As used herein, the term "heterocyclyl-Ci-galkyl" refers to a radical of the formula:

-Ci-galkyl-heterocyclyl.

As used herein, the term "heterocyclyl-amino" refers to a radical of the formula: -NH-heterocyclyl.

As used herein, the term "(heterocyclyl) ₂ -amino" refers to a radical of the formula: -N[(heterocyclyl) ₂ ].

As used herein, the term "heterocyclyl-amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-NH-heterocyclyl. As used herein, the term "(heterocyclyl) ₂ -amino-C ₁ _ ₈ alkyl" refers to a radical of the formula: -C ₁ _galkyl-N[(heterocyclyl) ₂ ] .

As used herein, the term "heterocyclyl-Ci-salkyl-amino-C^alkyl" refers to a radical of the formula: -Ci-salkyl-NH-C^alkyl-heterocyclyl.

As used herein, the term "(heterocyclyl-C ₁ _ ₈ alkyl) ₂ -amino-C ₁ _galkyl" refers to a radical of the formula: -C ₁ _ ₈ alkyl-N[(C ₁ _galkyl-heterocyclyl) ₂ ].

As used herein, the term "(heterocyclyl,C^alkyl)amino" refers to a radical of the formula: -NIXCi-salkylXheterocyclyl)] .

As used herein, the term "(heterocycly^Ci-galky^amino-Ci-galkyl" refers to a radical of the formula: -C _1-8 alkyl-N[(C _1-8 alkyl)(heterocyclyl)].

As used herein, the term "(heterocyclyl-Ci-salky^Ci-salky^amino-Ci-salkyl" refers to a radical of the formula: -C^alkyl-N Ci-salkylXC^alkyl-heterocyclyl)].

As used herein, the term "(heterocycly^Cs- _H cycloalkyl-Ci-salky^amino-Ci-salkyl" refers to a radical of the formula: -Ci-salkyl-Nfiheterocycly^iCi-salkyl-Cs-wcycloalkyl)].

As used herein, the term "heterocyclyl-carbonyl" refers to a radical of the formula:

-C(0)-heterocyclyl.

As used herein, the term "heterocyclyl-carbonyl-oxy" refers to a radical of the formula: -0-C(0)-heterocyclyl.

As used herein, the term "heterocyclyl-oxy" refers to a radical of the formula:

-O-heterocyclyl.

As used herein, the term "heterocyclyl-oxy-amino" refers to a radical of the formula: -NH-O-heterocyclyl.

As used herein, the term "(heterocyclyl-oxy) ₂ -amino" refers to a radical of the formula: -N[(-0-heterocyclyl) ₂ ].

As used herein, the term "(heterocyclyl-oxy^i-salky^amino" refers to a radical of the formula: -N[(C _1-8 alkyl)(-0-heterocyclyl)] .

As used herein, the term "(heterocyclyl-oxy-Ci-salky^C^alky^amino" refers to a radical of the formula: -N C^alkylXCi-salkyl-O-heterocyclyl)].

As used herein, the term "hydroxyl-Ci-salkoxy" refers to a radical of the formula: -O-Ci-salkyl-OH, wherein Ci-salkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals. As used herein, the term ''hydroxyl-Ci-galkyl'' refers to a radical of the formula:

-Ci-galkyl-OH, wherein Ci_galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxy radicals.

As used herein, the term "hydroxyl-Ci-salkyl-amino" refers to a radical of the formula: -NH-Ci-galkyl-OH, wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "(hydroxyl-Ci-galkyl amino" refers to a radical of the formula: -N(Ci-galkyl-OH)2, wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term '¾ydroxyl-Ci_galkyl-amino-Ci_galkyr refers to a radical of the formula: -Ci-galkyl-NH-Ci-galkyl-OH, wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "hydroxyl-Ci-galkyl-amino-Ci-galkyl-amino" refers to a radical of the formula: -NH-Ci-galkyl-NH-Ci-galkyl-OH, wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "(hydroxyl-Ci_galkyl,Ci_galkyl)amino" refers to a radical of the formula: -N^Ci-galkylXCi-galkyl-OH)], wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "(hydroxyl-Ci-galkyl,Ci-galkyl)amino-Ci-galkyl" refers to a radical of the formula: -Ci-galkyl-N Ci-galkylXCi-galkyl-OH)], wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "[(hydroxyl-Ci-galky^Ci-galky^amino- refers to a radical of the formula:

N Ci-galkylXCi-galkyl-OH)] }], wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "(hydroxyl-Ci-galkyl-amino-Ci-galkyl,Ci_galkyl)amino" refers to a radical of the formula: -N Ci-galkylXCi-galkyl-NH-Ci-galkyl-OH)], wherein Ci-galkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term "substituent" means positional variables on the atoms of a core molecule that are substituted at a designated atom position, replacing one or more hydrogens on the designated atom, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. A person of ordinary skill in the art should note that any carbon as well as heteroatom with valences that appear to be unsatisfied as described or shown herein is assumed to have a sufficient number of hydrogen atom(s) to satisfy the valences described or shown. In certain instances one or more substituents having a double bond (e.g., "oxo" or "=0") as the point of attachment may be described, shown or listed herein as part of a substituent group having a single bond as the point of attachment to the core structure of Formula (I) with the understanding that it would be clear to a person of ordinary skill in the art that a double bond was included within the scope of the substituent group showing only a single bond as the point of attachment to the core structure of Formula (I).

As used herein, the term "and the like," with reference to the definitions of chemical terms provided herein, means that variations in chemical structures that could be expected by one skilled in the art include, without limitation, isomers (including chain, branching or positional structural isomers), hydration of ring systems (including saturation or partial unsaturation of monocyclic, bicyclic or polycyclic ring structures) and all other variations where allowed by available valences which result in a stable compound.

For the purposes of this description, where one or more substituent variables for a compound of Formula (I) or a form thereof encompass functionalities incorporated into a compound of Formula (I), each functionality appearing at any location within the disclosed compound may be independently selected, and as appropriate, independently and/or optionally substituted.

As used herein, the terms "independently selected," or "each selected" refer to functional variables in a substituent list that may occur more than once on the structure of

Formula (I), the pattern of substitution at each occurrence is independent of the pattern at any other occurrence. Further, the use of a generic substituent variable on any formula or structure for a compound described herein is understood to include the replacement of the generic substituent with species substituents that are included within the particular genus, e.g. , aryl may be replaced with phenyl or naphthalenyl and the like, and that the resulting compound is to be included within the scope of the compounds described herein.

As used herein, the terms "each instance of or "in each instance, when present," when used preceding a phrase such as "...Cs-ncycloalkyl, Cs-ncycloalkyl-Ci-galkyl, aryl, aryl-Ci-galkyl, heteroaryl, heteroaryl-Ci-galkyl, heterocyclyl and heterocyclyl-Ci-galkyl," are intended to refer to the Cs-^cycloalkyl, aryl, heteroaryl and heterocyclyl ring systems when each are present either alone or as a substituent.

As used herein, the term "optionally substituted" means optional substitution with the specified substituent variables, groups, radicals or moieties.

As used herein, the terms "stable compound' or "stable structure" mean a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture and formulations thereof into an efficacious therapeutic agent.

Compound names used herein were obtained using the ACD Labs Index Name software provided by ACD Labs; and/or, were obtained using the naming function of

ChemDraw Ultra provided by CambridgeSoft. When the compound name disclosed herein conflicts with the structure depicted, the structure shown will supercede the use of the name to define the compound intended.

Compound Forms

As used herein, the term "form" means a compound of Formula (I) having a form selected from the group consisting of a free acid, free base, prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a free acid, free base or salt thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a salt thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is an isotopologue thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a stereoisomer, racemate, enantiomer or diastereomer thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a tautomer thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a pharmaceutically acceptable form.

In certain embodiments described herein, the compound of Formula (I) or a form thereof is isolated for use. As used herein, the term "isolated" means the physical state of a compound of Formula (I) or a form thereof after being isolated and/or purified from a synthetic process (e.g., from a reaction mixture) or natural source or combination thereof according to an isolation or purification process or processes described herein or which are well known to the skilled artisan (e.g., chromatography, recrystallization and the like) in sufficient purity to be characterizable by standard analytical techniques described herein or well known to the skilled artisan.

As used herein, the term "protected" means that a functional group in a compound of Formula (I) or a form thereof is in a form modified to preclude undesired side reactions at the protected site when the compound is subjected to a reaction. Suitable protecting groups will be recognized by those with ordinary skill in the art as well as by reference to standard textbooks such as, for example, T.W. Greene et al, Protective Groups in organic Synthesis (1991), Wiley, New York.

Prodrugs and solvates of the compounds described herein are also contemplated. As used herein, the term "prodrug" means a form of an instant compound (e.g., a drug precursor) that is transformed in vivo to yield an active compound of Formula (I) or a form thereof. The transformation may occur by various mechanisms (e.g., by metabolic and/or non-metabolic chemical processes), such as, for example, by hydrolysis and/or metabolism in blood, liver and/or other organs and tissues. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, "Pro-drugs as Novel Delivery Systems," Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.

In one example, when a compound of Formula (I) or a form thereof contains a carboxylic acid functional group, a prodrug can comprise an ester formed by the replacement of the hydrogen atom of the acid group with a functional group such as alkyl and the like. In another example, when a compound of Formula (I) or a form thereof contains a hydroxyl functional group, a prodrug form can be prepared by replacing the hydrogen atom of the hydroxyl with another functional group such as alkyl, alkylcarbonyl or a phosphonate ester and the like. In another example, when a compound of Formula (I) or a form thereof contains an amine functional group, a prodrug form can be prepared by replacing one or more amine hydrogen atoms with a functional group such as alkyl or substituted carbonyl.

Pharmaceutically acceptable prodrugs of compounds of Formula (I) or a form thereof include those compounds substituted with one or more of the following groups: carboxylic acid esters, sulfonate esters, amino acid esters, phosphonate esters and mono-, di- or triphosphate esters or alkyl substituents, where appropriate. As described herein, it is understood by a person of ordinary skill in the art that one or more of such substituents may be used to provide a compound of Formula (I) or a form thereof as a prodrug.

One or more compounds described herein may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and the description herein is intended to embrace both solvated and unsolvated forms.

As used herein, the term "solvate" means a physical association of a compound described herein with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. As used herein, "solvate" encompasses both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like.

One or more compounds described herein may optionally be converted to a solvate.

Preparation of solvates is generally known. The preparation of solvates of the antifungal fluconazole in ethyl acetate as well as from water has been described (see, M. Caira et al, J. Pharmaceutical Sci., 93(3), 601-611 (2004)). Similar preparations of solvates, hemisolvate, hydrates and the like have also been described (see, E.C. van Tonder et al, AAPS

PharmSciTech., 5(1), article 12 (2004); and A.L. Bingham et al, Chem. Commun., 603-604 (2001)). A typical, non-limiting process involves dissolving a compound in a desired amount of the desired solvent (organic or water or mixtures thereof) at a higher than ambient temperature, and cooling the solution at a rate sufficient to form crystals which are then isolated by standard methods. Analytical techniques such as, for example infrared spectroscopy, show the presence of the solvent (or water) in the crystals as a solvate (or hydrate).

As used herein, the term "hydrate" means a solvate wherein the solvent molecule is water.

The compounds of Formula (I) can form salts, which are intended to be included within the scope of this description. Reference to a compound of Formula (I) or a form thereof herein is understood to include reference to salt forms thereof, unless otherwise indicated. The term "salt(s)", as employed herein, denotes acidic salts formed with inorganic and/or organic acids, as well as basic salts formed with inorganic and/or organic bases. In addition, when a compound of Formula (I) or a form thereof contains both a basic moiety, such as, without limitation an amine moiety, and an acidic moiety, such as, but not limited to a carboxylic acid, zwitterions ("inner salts") may be formed and are included within the term "salt(s)" as used herein.

The term "pharmaceutically acceptable salt(s)", as used herein, means those salts of compounds described herein that are safe and effective (i.e., non-toxic, physiologically acceptable) for use in mammals and that possess biological activity, although other salts are also useful. Salts of the compounds of the Formula (I) may be formed, for example, by reacting a compound of Formula (I) or a form thereof with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization.

Pharmaceutically acceptable salts include one or more salts of acidic or basic groups present in compounds described herein. Embodiments of acid addition salts include, and are not limited to, acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, bitartrate, borate, bromide, butyrate, chloride, citrate, camphorate, camphorsulfonate, ethanesulfonate, formate, fumarate, gentisinate, gluconate, glucaronate, glutamate, iodide, isonicotinate, lactate, maleate, methanesulfonate, naphthalenesulfonate, nitrate, oxalate, pamoate, pantothenate, phosphate, propionate, saccharate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate (also known as tosylate), trifluoroacetate salts and the like. Certain embodiments of acid addition salts include chloride, bromide, acetate or trifluoroacetate salts.

Additionally, acids which are generally considered suitable for the formation of pharmaceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley- VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International ], of Pharmaceutics (1986) 33, 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D.C. on their website). These disclosures are incorporated herein by reference thereto.

Suitable basic salts include, but are not limited to, aluminum, ammonium, calcium, lithium, magnesium, potassium, sodium and zinc salts. Certain compounds described herein can also form pharmaceutically acceptable salts with organic bases (for example, organic amines) such as, but not limited to, dicyclohexylamines, t-butyl amines and the like, and with various amino acids such as, but not limited to, arginine, lysine and the like. Basic nitrogen- containing groups may be quarternized with agents such as lower alkyl halides (e.g. , methyl, ethyl, and butyl chlorides, bromides and iodides), dialkyl sulfates (e.g., dimethyl, diethyl, and dibutyl sulfates), long chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides and iodides), aralkyl halides (e.g., benzyl and phenethyl bromides) and the like.

All such acid salts and base salts are intended to be included within the scope of pharmaceutically acceptable salts as described herein. In addition, all such acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of this description.

Compounds of Formula (I) and forms thereof, may further exist in a tautomeric form (for example, the 4-hydroxy-2-pyridinone core of Formula (I) may exist in either the 2,4- dihydroxy-pyridine or the 2-hydroxy-4-pyridinone form). All such tautomeric forms are contemplated and intended to be included within the scope of the compounds of Formula (I) or a form thereof as described herein.

The compounds of Formula (I) or a form thereof may contain asymmetric or chiral centers, and, therefore, exist in different stereoisomeric forms. The present description is intended toinclude all stereoisomeric forms of the compounds of Formula (I) as well as mixtures thereof, including racemic mixtures.

The compounds described herein may include one or more chiral centers, and as such may exist as racemic mixtures (R/S) or as substantially pure enantiomers and diastereomers. The compounds may also exist as substantially pure (R) or (S) enantiomers (when one chiral center is present). In one embodiment, the compounds described herein are (S) isomers and may exist as enantiomerically pure compositions substantially comprising only the (S) isomer. In another embodiment, the compounds described herein are (R) isomers and may exist as enantiomerically pure compositions substantially comprising only the (R) isomer. As one of skill in the art will recognize, when more than one chiral center is present, the compounds described herein may also exist as a (R,R), (R,S), (S,R) or (S,S) isomer, as defined by IUPAC Nomenclature Recommendations.

As used herein, the term "substantially pure" refers to compounds consisting substantially of a single isomer in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100% of the single isomer. In one aspect of the description, a compound of Formula (I) or a form thereof is a substantially pure (S) enantiomer form present in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100%.

In one aspect of the description, a compound of Formula (I) or a form thereof is a substantially pure (R) enantiomer form present in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100%.

As used herein, a "racemate" is any mixture of isometric forms that are not

"enantiomeric ally pure", including mixtures such as, without limitation, in a ratio of about 50/50, about 60/40, about 70/30, or about 80/20.

In addition, the present description embraces all geometric and positional isomers. For example, if a compound of Formula (I) or a form thereof incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the description. Diastereomeric mixtures can be separated into their individual

diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and/or fractional crystallization. Enantiomers can be separated by use of chiral HPLC column or other chromatographic methods known to those skilled in the art. Enantiomers can also be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher' s acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Also, some of the compounds of Formula (I) may be atropisomers (e.g. , substituted biaryls) and are considered as part of this description.

All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds (including those of the salts, solvates, esters and prodrugs of the compounds as well as the salts, solvates and esters of the prodrugs), such as those which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, and diastereomeric forms, are contemplated within the scope of this description, as are positional isomers (such as, for example, 4-pyridyl and 3-pyridyl). Individual stereoisomers of the compounds described herein may, for example, be substantially free of other isomers, or may be present in a racemic mixture, as described supra.

The use of the terms "salt", "solvate", "ester", "prodrug" and the like, is intended to equally apply to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or isotopologues of the instant compounds.

The term "isotopologue" refers to isotopically-enriched compounds described herein which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ 0, ¹⁷ 0, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ³⁵ C1 and ³⁶ C1, respectively, each of which are also within the scope of this description.

Certain isotopically-enriched compounds described herein (e.g., those labeled with H and ¹⁴ C) are useful in compound and/or substrate tissue distribution assays. Tritiated (i.e., ³ H) and carbon- 14 (i.e., ¹⁴ C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e., H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances.

Polymorphic crystalline and amorphous forms of the compounds of Formula (I) and of the salts, solvates, hydrates, esters and prodrugs of the compounds of Formula (I) are further intended to be included in the present description.

Compound Uses

The present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound or a form thereof to the subject.

The present description further relates to use of the compound of Formula (I) or a form thereof for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof.

The present description further relates to use of the compound of Formula (I) or a form thereof having activity toward wild-type or drug-resistant N. gonorrhoeae. The present description also relates to use of a compound of Formula (I) or a form thereof having activity against aminoglycoside-resistant, beta-lactam-resistant,

cephalosporin-resistant, macrolide-resistant, quinolone-resistant or tetracycline-resistant N. gonorrhoeae .

The present description also relates to use of a compound of Formula (I) or a form thereof having activity against aminoglycoside-resistant (including drug-resistant forms of N. gonorrhoeae that are spectinomycin-resistant, streptomycin -resistant, and the like), beta- lactam-resistant (including drug-resistant forms of N. gonorrhoeae that are ampicillin- resistant, penicillin-resistant, and the like), cephalosporin-resistant (including drug-resistant forms of N. gonorrhoeae that are ceftriaxone-resistant, cefixime-resistant, and the like), macrolide-resistant (including drug-resistant forms of N. gonorrhoeae that are azithromycin- resistant, and the like), quinolone-resistant (including drug-resistant forms of N. gonorrhoeae that are ciprofloxacin-resistant, and the like) or tetracycline-resistant N. gonorrhoeae (including drug-resistant forms of N. gonorrhoeae that are tetracycline-resistant).

The present description also relates to use of the compound of Formula (I) or a form thereof having activity against ampicillin-resistant, azithromycin-resistant, ceftriaxone- resistant, cefixime-resistant, ciprofloxacin-resistant, penicillin-resistant, spectinomycin- resistant, streptomycin-resistant and tetracycline-resistant forms of N. gonorrhoeae.

The present description also relates to use of the compound of Formula (I) or a form thereof having activity against aminoglycoside-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against beta-lactam-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against cephalosporin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against macrolide-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against quinolone-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against tetracycline-resistant forms of

N. gonorrhoeae.

The present description also relates to use of the compound of Formula (I) or a form thereof having activity against ampicillin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against azithromycin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against ceftriaxone-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against cefixime-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against ciprofloxacin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against penicillin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against spectinomycin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against streptomycin-resistant forms of N. gonorrhoeae. The present description also relates to use of the compound of Formula (I) or a form thereof having activity against tetracycline -resistant forms of N. gonorrhoeae.

The present description further relates to use of the compound of Formula (I) or a form thereof in a combination therapy with known antibacterial or antibiotic agents to provide additive or synergistic activity, thus enabling the development of a combination product for the treatment of a wild-type or drug-resistant form of N. gonorrhoeae.

The compounds of the present description have demonstrated an ability to inhibit the replication of a wide variety of N. gonorrhoeae isolates. The instant compounds possess in vitro activity against a wide spectrum of N. gonorrhoeae isolates which have developed resistance to almost all known treatments and are expected to successfully treat wild-type or drug-resistant forms of N. gonorrhoeae compared to current antibacterial agents. The compounds are also effective in vivo and lack cellular toxicity. In addition to

monotherapeutic use, the instant compounds are useful in a combination therapy with current standard of care antibacterial or antibiotic agents, having additive or synergistic activity with one or more known antibacterial or antibiotic agents.

A combination therapy comprising compounds described herein in combination with one or more known antibacterial or antibiotic drugs may be used to treat wild-type or drug- resistant forms of N. gonorrhoeae regardless of whether N. gonorrhoeae is resistant or responsive to the known antibacterial or antibiotic drug.

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a combination therapy for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof and an effective amount of one or more antibiotic or

antibacterial agent(s).

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a combination therapy for treating or ameliorating wild-type or drug- resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof and an effective amount of one or more antibiotic or antibacterial agent(s).

An embodiment of the present description includes the use of a compound of Formula (I) or a form thereof in the preparation of a kit comprising the compound of Formula (I) or a form thereof and instructions for administering an effective amount of the compound of Formula (I) or a form thereof and an effective amount of one or more antibiotic or

antibacterial agent(s) in a combination therapy for treating or ameliorating N. gonorrhoeae in a subject in need thereof.

In one embodiment, the agents used in the combination therapy may include, without limitation, one or more agents selected from Amikacin, Amoxicillin, Ampicillin,

Arsphenamine, Azithromycin, Azlocillin, Aztreonam, Bacitracin, Capreomycin,

Carbenicillin, Cefaclor, Cefadroxil, Cefalexin, Cefalotin, Cefamandole, Cefazolin, Cefdinir, Cefditoren, Cefixime, Cefoperazone, Cefotaxime, Cefoxitin, Cefpodoxime, Cefprozil, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefuroxime, Chloramphenicol, Cilastatin, Ciprofloxacin, Clarithromycin, Clavulanate, Clindamycin, Clofazimine, CloxaciUin, Colistin, Cycloserine, Dalfopristin, Dapsone, Daptomycin, Dicloxacillin, Dirithromycin, Doripenem, Doxycycline, Enoxacin, Erythromycin, Ethambutol, Ethionamide, Flucloxacillin,

Fosfomycin, Furazolidone, Fusidic acid, Gatifloxacin, Gemifloxacin, Gentamicin, Imipenem, Isoniazid, Kanamycin, Levofloxacin, Lincomycin, Linezolid, Lomefloxacin, Loracarbef,

Mafenide, Meropenem, Methicillin, Metronidazole, Mezlocillin, Minocycline, Moxifloxacin, Mupirocin, Nafcillin, Nalidixic acid, Neomycin, Netilmicin, Nitrofurantoin, Norfloxacin, Ofloxacin, Oxacillin, Oxytetracycline, Paromomycin, Penicillin G, Penicillin V, Piperacillin, Platensimycin, Polymyxin B, Pyrazinamide, Quinupristin, Rapamycin, Rifabutin, Rifampicin, Rifampin, Rifapentine, Rifaximin, Roxithromycin, Silver sulfadiazine, Solithromycin, Spectinomycin, Streptomycin, Sulbactam, Sulfacetamide, Sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sulfanamide, Sulfasalazine, Sulfisoxazole, Tazobactam, Teicoplanin, Telavancin, Telithromycin, Temocillin, Tetracycline, Thiamphenicol, TicarciUin,

Tigecycline, Tinidazole, Tobramycin, Trimethoprim, Troleandomycin or Vancomycin.

In another embodiment, the agents used in the combination therapy may include, without limitation, one or more agents selected from Amikacin, Amoxicillin, Arsphenamine, Azlocillin, Aztreonam, Bacitracin, Capreomycin, Carbenicillin, Cefaclor, Cefadroxil, Cefalexin, Cefalotin (Cefalothin), Cefamandole, Cefazolin, Cefdinir, Cefditoren,

Cefoperazone, Cefotaxime, Cefoxitin, Cefpodoxime, Cefprozil, Ceftazidime, Ceftibuten, Ceftizoxime, Cefuroxime, Chloramphenicol, Cilastatin, Clarithromycin, Clavulanate, Clindamycin, Clofazimine, Cloxacillin, Colistin, Cycloserine, Dalfopristin, Dapsone, Daptomycin, Dicloxacillin, Dirithromycin, Doripenem, Doxycycline, Enoxacin,

Erythromycin, Ethambutol, Ethionamide, Flucloxacillin, Fosfomycin, Furazolidone, Fusidic acid, Gatifloxacin, Gemifloxacin, Gentamicin, Imipenem, Isoniazid, Kanamycin,

Levofloxacin, Lincomycin, Linezolid, Lomefloxacin, Loracarbef, Mafenide, Meropenem, Methicillin, Metronidazole, Mezlocillin, Minocycline, Moxifloxacin, Mupirocin, Nafcillin, Nalidixic acid, Neomycin, Netilmicin, Nitrofurantoin, Norfloxacin, Ofloxacin, Oxacillin, Oxytetracycline, Paromomycin, Piperacillin, Platensimycin, Polymyxin B, Pyrazinamide, Quinupristin, Rapamycin, Rifabutin, Rifampicin, Rifampin, Rifapentine, Rifaximin,

Roxithromycin, Silver sulfadiazine, Solithromycin, Sulbactam, Sulfacetamide, Sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Tazobactam, Teicoplanin, Telavancin, Telithromycin, Temocillin, Thiamphenicol, TicarciUin, Tigecycline, Tinidazole, Tobramycin, Trimethoprim, Troleandomycin or Vancomycin.

In another embodiment, the agents used in the combination therapy may include, without limitation, one or more agents selected from Amoxicillin, Ampicillin, Azithromycin, Ciprofloxacin, Doxycycline, Enoxacin, Erythromycin, Gatifloxacin, Gemifloxacin,

Gentamicin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Rapamycin, Solithromycin, Spectinomycin, Streptomycin, Tetracycline or Vancomycin.

In another embodiment, the agents used in the combination therapy may particularly include one or more agents selected from Amoxicillin, Azithromycin, Ciprofloxacin, Doxycycline, Enoxacin, Erythromycin, Gatifloxacin, Gemifloxacin, Gentamicin,

Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin,

Rapamycin, Solithromycin or Vancomycin. In another embodiment, the agents used in the combination therapy may include, without limitation, one or more agents selected from Ampicillin, Azithromycin, Cefixime, Ceftriaxone, Ciprofloxacin, Penicillin G, Penicillin V, Spectinomycin, Streptomycin or Tetracycline.

Accordingly, the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating wild- type forms of N. gonorrhoeae, for treating or ameliorating drug-resistant forms of N. gonorrhoeae or for treating or ameliorating multidrug resistant forms of N. gonorrhoeae.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae resulting from wild-type forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae resulting from drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating wild-type or drug-resistant forms N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating wild-type or drug-resistant forms N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject. One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating wild-type forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating wild-type forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating wild-type forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.

One embodiment of the use of the present description relates to use of a compound of

Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the preparation of a kit comprising the compound of Formula (I) or a form thereof and instructions for administering the compound for treating or ameliorating N. gonorrhoeae in a subject in need thereof. One embodiment of the use of the present description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of a compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to use of a compound of

Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the the medicament to the subject.

In one respect, for each of such embodiments, the subject is treatment naive. In another respect, for each of such embodiments, the subject is not treatment naive.

As used herein, the term "treating" refers to: (i) preventing a disease, disorder or condition from occurring in a subject that may be predisposed to the disease, disorder and/or condition but has not yet been diagnosed as having the disease, disorder and/or condition; (ii) inhibiting a disease, disorder or condition, i.e., arresting the development thereof; and/or (iii) relieving a disease, disorder or condition, i.e., causing regression of the disease, disorder and/or condition.

As used herein, the term "subject" refers to an animal or any living organism having sensation and the power of voluntary movement, and which requires oxygen and organic food. Nonlimiting examples include members of the human, primate, equine, porcine, bovine, murine, rattus, canine and feline specie. In some embodiments, the subject is a mammal or a warm-blooded vertebrate animal. In other embodiments, the subject is a human. As used herein, the term "patient" may be used interchangeably with "subject" and "human".

Another aspect of the description particularly relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae resulting from wild type forms of N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof.

Another aspect of the description particularly relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae resulting from drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof. One aspect of the description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against N. gonorrhoeae clinical isolates and their derivatives selected from ATCC penicillin- sensitive wild- type N. gonorrhoeae FA 19 (ATCC BAA- 1838), ATCC streptomycin-resistant (streptomycin ) N. gonorrhoeae FA1090 (ATCC 700825; GenBank Acc. No. AE004969), ATCC N. gonorrhoeae MS11 (ATCC BAA-1833) and ATCC wild-type N. gonorrhoeae 49226 (ATCC 49226) (see, http://www.atcc.org).

Another aspect of the description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against N. gonorrhoeae isolates engineered from clinical isolate FA 19 to contain mutations in gyrA and parC, including those selected from ciprofloxacin-resistant (ciprofloxacin ) N. gonorrhoeae AK1 (gyrAgi _/ g ₅ ) and

ciprofloxacin N. gonorrhoeae AK2 (gyrAgws, parC%e) (see, Anjali N. Kunz, Afrin A.

Begum, Hong Wu, Jonathan A. D'Ambrozio, James M. Robinson, William M. Shafer, Margaret C. Bash and Ann E. Jerse. Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations. J. Infect Dis., 2012, Jun 15; 205(12): 1821-9).

Another aspect of the description relates to a method of use for a compound of

Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against N. gonorrhoeae World Health

Organization (WHO) isolates selected from: tetracycline ER N. gonorrhoeae 13477 (WHO tetracycline intermediate resistant isolate F), ciprofloxacin ER /tetracycline R N. gonorrhoeae 13478 (WHO ciprofloxacin intermediate resistant and tetracycline resistant isolate G), quinoline N. gonorrhoeae 13479 (WHO quinolone high level resistant isolate K), MDR N. gonorrhoeae 13480 (WHO multi-drug resistant isolate L) and MD ^∑ R N. gonorrhoeae 13481 (WHO multi-drug intermediate resistant isolate M) (see, Unemo M, Fasth O, Fredlund H, Limnios A, Tapsall J. Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J.

Antimicrobial Chemother., 2009, Jun; 63(6): 1142-51). Another aspect of the description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against the

ciprofloxacin XDR /cefixime XDR /ceftriaxone XDR extensively drug resistant N. gonorrhoeae F89 (see, Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother., 2012, Mar; 56(3): 1273-80).

Another aspect of the description relates to a method of use for a compound of

Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against a N. gonorrhoeae isolate engineered from WHO isolate F (N. gonorrhoeae 13477), where DNA from FA1090 was isolated and used to transform 13477 with the streptomycin determinant. The resulting isolate SP1364 is streptomycin at >1250 μg/mL.

Another aspect of the description relates to a method of use for a compound of Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against a N. gonorrhoeae clinical isolate LG24 (see, Garvin LE, Bash MC, Keys C, Warner DM, Ram S, Shafer WM and Jerse AE.

Phenotypic and genotypic analyses of Neisseria gonorrhoeae isolates that express frequently recovered PorB PIA variable region types suggest that certain Pla porin sequences confer a selective advantage for urogenital tract infection. Infect Immun., 2008, Aug;76(8):3700-9).

Another aspect of the description relates to a method of use for a compound of

Formula (I) or a form thereof for treating or ameliorating N. gonorrhoeae in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I) or a form thereof having activity against N. gonorrhoeae clinical isolates selected from penicillin-resistant (penicillin ) N. gonorrhoeae LGB3, tetracycline-resistant

(tetracycline R ) N. gonorrhoeae LGB24 and ampicillin-resistant (ampicillin R ) N. gonorrhoeae LGB50 (see, McKnew DL, Lynn F, Zenilman JM, Bash MC. Porin variation among clinical isolates of N. gonorrhoeae over a 10-year period, as determined by Por variable region typing. J. Infect Dis., 2003, Apr 15;187(8): 1213-22). An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate wild- type N. gonorrhoeae 49226 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate clinical isolate N. gonorrhoeae LG24 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate

N. gonorrhoeae MS 11 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate ampicillin N. gonorrhoeae LGB50 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate penicillin-sensitive N. gonorrhoeae FA19 or LGB3 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate streptomycin N. gonorrhoeae FA 1090 or SP1364 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate ciprofloxacin N. gonorrhoeae AK1 or AK2 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate N. gonorrhoeae caused by an isolate selected from 13477, 13478, 13479, 13480 or 13481 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate tetracycline N. gonorrhoeae LGB24 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use for a compound of Formula (I) or a form thereof to treat or ameliorate ciprofloxacin XDR /cefixime XDR /ceftriaxone XDR N. gonorrhoeae F89 in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

As used herein, the terms "effective amount" or "therapeutically effective amount" mean an amount of compound of Formula (I) or a form, composition or medicament thereof effective in inhibiting the above-noted diseases and thus producing the desired therapeutic, ameliorative, inhibitory or preventative effect in a subject in need thereof.

The dose administered to achieve an effective target plasma concentration may also be administered based upon the weight of the subject or patient. Doses administered on a weight basis may be in the range of about 0.001 mg/kg/day to about 3500 mg/kg/day, or about 0.01 mg/kg/day to about 2000 mg/kg/day, or about 0.01 mg/kg/day to about 1500 mg/kg/day, or about 0.01 mg/kg/day to about 1000 mg/kg/day, or about 0.01 mg/kg/day to about 600 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day to about 300 mg/kg/day, or about 0.015 mg/kg/day to about 200 mg/kg/day, or about 0.02 mg/kg/day to about 100 mg/kg/day, or about 0.025 mg/kg/day to about 100 mg/kg/day, or about 0.03 mg/kg/day to about 100 mg/kg/day, wherein said amount is orally administered once (once in approximately a 24 hour period), twice (once in approximately a 12 hour period) or thrice (once in approximately an 8 hour period) daily according to subject weight.

In certain embodiments, the effective amount will be in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.1 mg to about 500 mg/kg/day, or about 1.0 mg/day to about 500 mg/kg/day, in single, divided, or a continuous dose for a patient or subject having a weight in a range of between about 40 to about 200 kg (which dose may be adjusted for patients or subjects above or below this range, particularly children under 40 kg). The typical adult subject is expected to have a median weight in a range of about 70 kg.

In another embodiment, where daily doses are adjusted based upon the weight of the subject or patient, compounds described herein may be formulated for delivery at about 0.02, 0.025, 0.03, 0.05, 0.06, 0.075, 0.08, 0.09, 0.10, 0.20, 0.25, 0.30, 0.50, 0.60, 0.75, 0.80, 0.90, 1.0, 1.10, 1.20, 1.25, 1.50, 1.75, 2.0, 3.0, 5.0, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 400 or 500 mg/kg/day. Daily doses adjusted based upon the weight of the subject or patient may be administered as a single, divided, or continuous dose. In embodiments where a dose of compound is given more than once per day, the dose may be administered twice, thrice, or more per day.

In certain embodiments, the "effective amount" of a compound of Formula (I) or a form thereof for use in the manufacture of a medicament, the preparation of a pharmaceutical kit or in a method of treating or ameliorating N. gonorrhoeae in a subject in need thereof, is intended to include an amount in a range of from about 0.001 mg to about 3500 mg administered daily; 1.0 mg to about 3500 mg administered daily; 1.0 mg to about 1500 mg administered daily; 1.0 mg to about 1000 mg administered daily; 10.0 mg to about 600 mg administered daily; 0.5 mg to about 2000 mg administered daily; or, an amount in a range of from about 5.0 mg to about 300 mg administered daily.

In one example, the effective amount may be the amount required to treat

N. gonorrhoeae in a subject or the amount required to inhibit N. gonorrhoeae replication in a subject or cell, or more specifically, in a human subject or in a human cell.

In some instances, the desired effect can be determined by analyzing the presence of bacterial DNA. The effective amount for a subject will depend upon various factors, including the subject's body weight, size and health. Effective amounts for a given patient can be determined by routine experimentation that is within the skill and judgment of the clinician.

For any compound, the effective amount can be estimated initially either in cell culture assays or in relevant animal models, such as a mouse, chimpanzee, marmoset or tamarin animal model. Relevant animal models may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED ₅₀ (the dose therapeutically effective in 50% of the population) and LD ₅₀ (the dose lethal to 50% of the population). The dose ratio between therapeutic and toxic effects is therapeutic index, and can be expressed as the ratio, LD ₅₀ /ED ₅₀ . In some embodiments, the effective amount is such that a large therapeutic index is achieved. In further embodiments, the dosage is within a range of circulating concentrations that include an ED ₅₀ with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration.

More specifically, the concentration-biological effect relationships observed with regard to a compound of Formula (I) or a form thereof indicate a target plasma concentration ranging from approximately 0.001 μg/mL to approximately 50 μg/mL, from approximately 0.01 μg/mL to approximately 20 μg/mL, from approximately 0.05 μg/mL to approximately 10 μg/mL, or from approximately 0.1 μg/mL to approximately 5 μg/mL. To achieve such plasma concentrations, the compounds described herein may be administered at doses that vary, such as, for example, without limitation, from 0.1 ng to 10,000 mg, depending upon the route of administration in single, divided, or continuous doses for a patient weighing between about 10 to about 100 kg (which dose may be adjusted for patients within this weight range, particularly for children under 40 kg).

The exact dosage will be determined by the practitioner, in light of factors related to the subject. Dosage and administration may be adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, general health of the subject, ethinicity, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, experience with other antibacterial therapies, and tolerance/response to therapy. Long-acting pharmaceutical compositions may be administered every 2, 3 or 4 days, once every week, or once every two weeks depending on half-life and clearance rate of the particular formulation.

The compounds and compositions described herein may be administered to the subject via any drug delivery route known in the art. Nonlimiting examples include oral, ocular, rectal, buccal, topical, nasal, ophthalmic, subcutaneous, intramuscular, intraveneous (bolus and infusion), intracerebral, transdermal, and pulmonary routes of administration. Metabolites of the Compounds

Also included within the scope of the present description are the use of in vivo metabolic products of the compounds described herein. Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification and the like of the administered compound, primarily due to enzymatic processes. Accordingly, the description includes the use of compounds produced by a process comprising contacting a compound described herein with a mammalian tissue or a mammal for a period of time sufficient to yield a metabolic product thereof.

Such products typically are identified by preparing a radio-labeled isotopologue (e.g.,

¹⁴ C or ³ H) of a compound described herein, administering the radio-labeled compound in a detectable dose (e.g., greater than about 0.5 mg/kg) to a mammal such as a rat, mouse, guinea pig, dog, monkey or human, allowing sufficient time for metabolism to occur (typically about 30 seconds to about 30 hours), and identifying the metabolic conversion products from urine, bile, blood or other biological samples. The conversion products are easily isolated since they are "radiolabeled" by virtue of being isotopically-enriched (others are isolated by the use of antibodies capable of binding epitopes surviving in the metabolite). The metabolite structures are determined in conventional fashion, e.g., by MS or NMR analysis. In general, analysis of metabolites may be done in the same way as conventional drug metabolism studies well-known to those skilled in the art. The conversion products, so long as they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the compounds described herein even if they possess no biological activity of their own.

Pharmaceutical Compositions

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a pharmaceutical composition for treating or ameliorating

N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof in admixture with one or more

pharmaceutically acceptable excipient(s).

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a pharmaceutical composition for treating or ameliorating wild-type or drug-resistant forms of N. gonorrhoeae in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof in admixture with one or more pharmaceutically acceptable excipient(s).

An embodiment of the present description includes the use of a pharmaceutical composition of the compound of Formula (I) or a form thereof in the preparation of a kit comprising the pharmaceutical composition of the compound of Formula (I) or a form thereof and instructions for administering the compound for treating or ameliorating N. gonorrhoeae in a subject in need thereof. As used herein, the term "composition" means a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.

The pharmaceutical composition may be formulated to achieve a physiologically compatible pH, ranging from about pH 3 to about pH 11. In some embodiments, the pharmaceutical composition is formulated to achieve a pH of from about pH 3 to about pH 7. In other embodiments, the pharmaceutical composition is formulated to achieve a pH of from about pH 5 to about pH 8.

The term "pharmaceutically acceptable excipient" refers to an excipient for administration of a pharmaceutical agent, such as the compounds described herein. The term refers to any pharmaceutical excipient that may be administered without undue toxicity. Pharmaceutically acceptable excipients may be determined in part by the particular composition being administered, as well as by the particular mode of administration and/or dosage form. Nonlimiting examples of pharmaceutically acceptable excipients include carriers, solvents, stabilizers, adjuvants, diluents, etc. Accordingly, there exists a wide variety of suitable formulations of pharmaceutical compositions for the instant compoounds described herein {see, e.g., Remington's Pharmaceutical Sciences).

Suitable excipients may be carrier molecules that include large, slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, and inactive antibodies. Other exemplary excipients include antioxidants such as ascorbic acid; chelating agents such as EDTA;

carbohydrates such as dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose {e.g., hydroxypropylmethylcellulose, also known as HPMC), stearic acid; liquids such as oils, water, saline, glycerol and ethanol; wetting or emulsifying agents; pH buffering substances; and the like. Liposomes are also included within the definition of pharmaceutically acceptable excipients.

The pharmaceutical compositions described herein may be formulated in any form suitable for the intended use described herein. Suitable formulations for oral administration include solids, liquid solutions, emulsions and suspensions, while suitable inhaleable formulations for pulmonary administration include liquids and powders. Alternative formulations include syrups, creams, ointments, tablets, and lyophilized solids which can be reconstituted with a physiologically compatible solvent prior to administration. When intended for oral use for example, tablets, troches, lozenges, aqueous or oil suspensions, non-aqueous solutions, dispersible powders or granules (including micronized particles or nanoparticles), emulsions, hard or soft capsules, syrups or elixirs may be prepared. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents including sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a palatable preparation.

Pharmaceutically acceptable excipients suitable for use in conjunction with tablets include, for example, inert diluents, such as celluloses, calcium or sodium carbonate, lactose, calcium or sodium phosphate; disintegrating agents, such as croscarmellose sodium, cross- linked povidone, maize starch, or alginic acid; binding agents, such as povidone, starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. Tablets may be uncoated or may be coated by known techniques including

microencapsulation to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed.

Formulations for oral use may be also presented as hard gelatin capsules where the active ingredient is mixed with an inert solid diluent, for example celluloses, lactose, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with non-aqueous or oil medium, such as glycerin, propylene glycol, polyethylene glycol, peanut oil, liquid paraffin or olive oil.

In other embodiments, pharmaceutical compositions described herein may be formulated as suspensions comprising a compound of Formula (I) or a form thereof in admixture with one or more pharmaceutically acceptable excipient(s) suitable for the manufacture of a suspension. In yet other embodiments, pharmaceutical compositions described herein may be formulated as dispersible powders and granules suitable for preparation of a suspension by the addition of one or more excipient(s).

Excipients suitable for use in connection with suspensions include suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methylcelluose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, dispersing or wetting agents such as a naturally occurring phosphatide (e.g. , lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g. , polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g. , heptadecaethyleneoxycethanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol anhydride (e.g. , polyoxyethylene sorbitan monooleate); and thickening agents, such as carbomer, beeswax, hard paraffin or cetyl alcohol. The suspensions may also contain one or more preservatives such as acetic acid, methyl and/or n-propyl p-hydroxy-benzoate; one or more coloring agents; one or more flavoring agents; and one or more sweetening agents such as sucrose or saccharin.

The pharmaceutical compositions described herein may also be in the form of oil-in- water emulsions. The oily phase may be a vegetable oil, such as olive oil or arachis oil, a mineral oil, such as liquid paraffin, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth; naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids;

hexitol anhydrides, such as sorbitan monooleate; and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. The emulsion may also contain sweetening and flavoring agents. Syrups and elixirs may be formulated with sweetening agents, such as glycerol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, a flavoring or a coloring agent.

Additionally, the pharmaceutical compositions described herein may be in the form of a sterile injectable preparation, such as a sterile injectable aqueous emulsion or oleaginous suspension. Such emulsion or suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,2-propane-diol. The sterile injectable preparation may also be prepared as a lyophilized powder. Among the acceptable vehicles and solvents that may be employed are water, Ringer' s solution, and isotonic sodium chloride solution. In addition, sterile fixed oils may be employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid may likewise be used in the preparation of injectables.

The compounds described herein may be substantially insoluble in water and sparingly soluble in most pharmaceutically acceptable protic solvents and vegetable oils, but generally soluble in medium-chain fatty acids (e.g. , caprylic and capric acids) or triglycerides and in propylene glycol esters of medium-chain fatty acids. Thus, contemplated in the description are compounds which have been modified by substitutions or additions of chemical or biochemical moieties which make them more suitable for delivery (e.g., increase solubility, bioactivity, palatability, decrease adverse reactions, etc.), for example by esterification, glycosylation, PEGylation, etc.

In some embodiments, the compound described herein is formulated for oral administration in a lipid-based composition suitable for low solubility compounds. Lipid- based formulations can generally enhance the oral bioavailability of such compounds. As such, pharmaceutical compositions described herein may comprise a effective amount of a compound of Formula (I) or a form thereof, together with at least one pharmaceutically acceptable excipient selected from medium chain fatty acids or propylene glycol esters thereof (e.g., propylene glycol esters of edible fatty acids such as caprylic and capric fatty acids) and pharmaceutically acceptable surfactants, such as polysorbate 20 or 80 (also referred to as Tween 20 or Tween 80, respectively) or polyoxyl 40 hydrogenated castor oil.

In other embodiments, the bioavailability of low solubility compounds may be enhanced using particle size optimization techniques including the preparation of

nanoparticles or nanosuspensions using techniques known to those skilled in the art. The compound forms present in such preparations include amorphous, partially amorphous, partially crystalline or crystalline forms.

In alternative embodiments, the pharmaceutical composition may further comprise one or more aqueous solubility enhancer(s), such as a cyclodextrin. Nonlimiting examples of cyclodextrin include hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of α-, β-, and γ-cyclodextrin, and hydroxypropyl- β-cyclodextrin (HPBC). In some embodiments, the pharmaceutical composition further comprises HPBC in a range of from about 0.1% to about 20%, from about 1% to about 15%, or from about 2.5% to about 10%. The amount of solubility enhancer employed may depend on the amount of the compound in the composition.

Preparation of Compounds

General Synthetic Examples

As disclosed herein, many of the starting materials used are commercially available or can be prepared using the routes described below using techniques known to those skilled in the art. General Schemes

Compounds of Formula (I) can be prepared as described in the Schemes below. Scheme 1

Rx2 = Rsb or CH ₂ OTBS

General Procedure for Scheme 1

Halogenated pyridones of Type lc (where Hal represents a halogen such as CI) are prepared through the reaction of nitriles of Type lb with malonyl halides of Type la.

Pyridines of Type Id are prepared from pyridones of Type lc via Mitsunobu reaction with a suitable dialkyl azodicarboxylate (such as diisopropyl azodicarboxylate and the like) and benzyl alcohol.

Functionalized pyridines of Type le are prepared from pyridines of Type Id via deprotonation of pyridine of Type Id with an appropriate alkyl lithium species (such as n- BuLi and the like) followed by reaction with benzylchloroformate.

Boronic ester intermediates of Type lg are prepared from aryl halides of Type If (where Hal represents a halogen such as Br or I, R _xl is either Rs _a or a suitable protecting group such as Boc, and R _x2 is R _5b or CH ₂ OTBS (CH ₂ -0-tert-butyldimethylsilyl)) via a Miyaura borylation reaction with a suitable Pd catalyst (such as PdCl ₂ (dppf) and the like) and an appropriate diboron ester (such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2- dioxaborolane and the like).

Biaryl intermediates of Type lh are prepared from the respective boronic esters of Type lg via Pd catalyzed Suzuki coupling with functionalized pyridines of Type le in the presence of a suitable phosphine ligand (such as t-Bu ₃ P and the like) in a suitable biphasic mixture (such as a mixture of THF and water and the like).

Compounds of Type li, representative of Compound Formula (I), are prepared from biaryl intermediates of Type lh by global benzyl group deprotection via suitable methods (such as hydrogenation in the presence of a suitable Pd catalyst (such as Pd/C and the like) or treatment with a suitable acid (such as TFA and the like).

Scheme 2

General Procedure for Scheme 2

Boronic ester intermediates of Type 2b are prepared from 6-haloindoles of Type 2a (where Hal represents a halogen such as Br or I) via a Miyaura borylation reaction with a suitable Pd catalyst (such as PdCl ₂ (dppf) and the like) and an appropriate diboron ester (such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2-dioxaborolane and the like).

Biaryl pyridines of Type 2c are prepared from the corresponding boronic esters of

Type 2b through a Pd catalyzed Suzuki coupling with functionalized pyridines of Type le in the presence of a suitable phosphine ligand (such as t-Bu ₃ P and the like) in a suitable biphasic mixture (such as a mixture of THF and water and the like).

Indoles of Type 2d are prepared from the corresponding N-Boc amines of Type 2c via Boc cleavage using a suitable acid (such as TFA and the like) followed by treatment with an appropriate aldehyde in the presence of a hydride source (such as NaBH(OAc) ₃ and the like).

Compounds of Type 2e, representative of Compound Formula (I), are prepared via global benzyl group deprotection of pyridines of Type 2d with a suitable acid (such as TFA and the like).

Scheme 3

General Procedure for Scheme 3

Amides of Type 3b are prepared via treatment of oximes of Type 3a (where Hal represents a halogen such as Br or I) with an acid (such as PPA and the like).

Boc-protected amines of Type 3c are prepared via reduction of amides of Type 3b with a suitable hydride source (such as borane and the like) followed by treatment with Boc ₂ 0.

Boronic ester intermediates of Type 3d are prepared from amines of Type 3c via a Miyaura borylation reaction with a suitable Pd catalyst (such as PdCl ₂ (dppf) and the like) and an appropriate diboron ester (such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2- dioxaborolane and the like). Biaryl pyridines of Type 3e are prepared from the corresponding boronic esters of Type 3d through a Pd catalyzed Suzuki coupling with functionalized pyridines of Type le in the presence of a suitable phosphine ligand (such as t-Bu ₃ P and the like) in a suitable biphasic mixture (such as a mixture of THF and water and the like).

Substituted biaryl pyridines of Type 3f are prepared from the corresponding N-Boc amines of Type 3e via Boc cleavage using a suitable acid (such as TFA and the like) followed by treatment with an appropriate aldehyde in the presence of a hydride source (such as NaBH(OAc) ₃ and the like).

Compounds of Type 3g, representative of Compound Formula (I), are prepared via global benzyl group deprotection of pyridines of Type 3f with a suitable acid (such as TFA and the like).

Scheme 4

General Procedure for Scheme 4

Boronic ester intermediates of Type 4b are prepared from 6-haloindoles of Type 4a (where Hal represents a halogen such as Br or I) via a Miyaura borylation reaction with a suitable Pd catalyst (such as PdCl ₂ (dppf) and the like) and an appropriate diboron ester (such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2-dioxaborolane and the like).

Biaryl pyridines of Type 4c are prepared from the corresponding boronic esters of

Type 4b through a Pd catalyzed Suzuki coupling with functionalized pyridines of Type le in the presence of a suitable phosphine ligand (such as t-Bu ₃ P and the like) in a suitable biphasic mixture (such as a mixture of THF and water and the like).

Compounds of Type 4d, representative of Compound Formula (I), are accessed via a three-step process: Step 1, reductive amination with a primary alkylamine in the presence of a hydride source (such as NaBH ₄ and the like); Step 2, reductive amination with an appropriate aldehyde in the presence of a hydride source (such as NaBH(OAc) ₃ and the like); and, Step 3, global benzyl group deprotection with a suitable acid (such as TFA and the like).

Schem 5

General Procedure for Scheme 5

Boronic ester intermediates of Type 5b are prepared from halogenated anilines of Type 5a (where Hal represents a halogen such as Br or I) via a Miyaura borylation reaction with a suitable Pd catalyst (such as PdCl ₂ (dppf) and the like) and an appropriate diboron ester (such as 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-l,3,2-dioxaborolane and the like).

Biaryl intermediates of Type 5c are prepared from the respective boronic esters of

Type 5b via Pd catalyzed Suzuki coupling with functionalized pyridines of Type le in the presence of a suitable phosphine ligand (such as t-Bu P and the like) in a suitable biphasic mixture (such as a mixture of THF and water and the like).

Compounds of Type 5d, representative of Compound Formula (I), are prepared from biaryl pryidines of Type 5c by global deprotection via suitable methods (such as

hydrogenation in the presence of a suitable Pd catalyst (such as Pd/C and the like).

Specific Examples

To assist in understanding the present description, the following specific examples are included. The experiments relating to this description should not, of course, be construed as specifically limiting the description and such variations of the description, now known or later developed, which would be within the purview of one skilled in the art are considered to fall within the scope of the description as described herein and hereinafter claimed.

Other than in the working examples, unless indicated to the contrary, all numbers expressing quantities of ingredients, reaction conditions, experimental data, and so forth used in the specification and claims are to be understood as being modified by the term "about". Accordingly, all such numbers represent approximations that may vary depending upon the desired properties sought to be obtained by a reaction or as a result of variable experimental conditions. Therefore, within an expected range of experimental reproducibility, the term "about" in the context of the resulting data, refers to a range for data provided that may vary according to a standard deviation from the mean. As well, for experimental results provided, the resulting data may be rounded up or down to present data consistently, without loss of significant figures. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding techniques.

While the numerical ranges and parameters setting forth the broad scope of the description are approximations, the numerical values set forth in the working examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

Synthetic Examples

Greater details of the present description are provided with reference to the following non-limiting examples, which are offered to more fully illustrate the description, but are not to be construed as limiting the scope thereof. The examples illustrate the preparation of certain compounds described herein, and the testing of these compounds in vitro and/or in vivo. Those of skill in the art will understand that the techniques described in these examples represent techniques described by the inventors to function well in the practice of the description, and as such constitute preferred modes for the practice thereof. However, those of skill in the art should appreciate in light of the present disclosure that many changes can be made to the specific methods that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the description. For example, various conditions were used to obtain LC-MS characterization for the compounds described herein. Unless indicated otherwise for certain compounds, the 2 Minute Method was used, having the following column and mobile phase ratios:

Column: Acquity UPLC HSS C18 Column 2.1 x 50 mm, 1.8μπι

Mobile Phase A: H ₂ O/0.1% HC0 ₂ H

Mobile Phase B : Acetonitrile/0.1 % HC0 ₂ H

Flow

Gradient Time (min) %A %B

(mL/min)

1 0 0.8 100 0

2 0.2 0.8 100 0

3 1.5 0.8 0 100

4 2.0 0.8 100 0

As used above, and throughout this description, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings:

Abbreviation Meaning

AcOH or HOAc acetic acid

ACN or MeCN acetonitrile

4A MS 4 Angstrom Molecular Sieves

Atm atmosphere

Bn benzyl

BnBr benzyl bromide

BnO or OBn benzyloxy

BnOH benzyl alcohol

Boc ie/t-butoxycarbonyl

Boc ₂ 0 or (Boc) ₂ 0 di-iert-butyl dicarbonate

BORSM based on recovered starting material

Cbz benzyloxycarbonyl

CDI 1 , 1 '-carbonyldiimidazole

DCE dichloroethane

DCM dichloromethane (CH ₂ C1 ₂ ) Abbreviation Meaning

DDQ 2.3- dichloro-5,6-dicyano-l,4-benzoquinone

DIAD diisopropyl azodicarboxylate

DIBAL-H diisobutylaluminium hydride

DMF dimethyl formamide

DMA dimethylacetamide

DMAP 4-dimethylaminopyridine

DMB 2.4- dimethoxybenzyl

DMSO dimethylsulfoxide

EA or EtOAc ethyl acetate

EtOH ethanol

Et ₂ 0 diethyl ether

HPLC high performance liquid chromatography h/hr/min/s hour(h or hr)/minute(min)/second(s)

KOAc potassium acetate

LAH lithium aluminium hydride

LC/MS, LCMS or liquid chromatographic mass spectroscopy

LDA lithium diisopropylamide

Mel methyl iodide

MeOH methanol

Me ₂ NH or NHMe ₂ dimethyl amine

MS mass spectroscopy

NaBH(OAc) ₃ sodium triacetoxyborohydride

NBS N-bromo succinimide

NIS N-iodo succinimide

NMO N-methylmorpholine-N-oxide

n-BuLi n-butyl lithium Abbreviation Meaning

NMR nuclear magnetic resonance

Pd/C palladium on carbon

Pd ₂ (dba) ₃ tris(dibenzylideneacetone)dipalladium(0)

PdCl ₂ dppf [1,1 '-bis(diphenylphosphino)ferrocene]

dichloropalladium(II)

Pd(PPh ) ₄ tetrakis(triphenylphosphine)palladium

Ph ₂ 0 diphenyl ether

Pin pinacol

PPA polyphosphoric acid

PPh ₃ triphenylphosphine

Psi pounds per square inch pressure

PTFE polytetrafluoroethylene

RT retention time

rt room temperature

RCM ring closing methathesis

S-Phos 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl

TBAF tetra-n-butylammonium fluoride

TBS tert-butyldimethylsilyl

TBSC1 tert-butyldimethylsilyl chloride

t-BuOK potassium tert-butoxide

t-Bu ₃ P tert-butyl phosphine

TEA or NEt ₃ triethylamine

TFA trifluoroacetic acid

THF tetrahydrofuran

THP tetrahydro-2H-pyranyl

THPO or OTHP tetrahydro-2H-pyran-2-yl-oxy Abbreviation Meaning

TIPS-H triisopropyl silane

TLC thin layer chromatography

TMSI trimethylsilyl iodide

TMSOK potassium trimethylsilanolate

TPAP -propylammonium perruthenate

Example 1

5-Ethyl-6-(5-fluoro-lH-indol-6-yl)-4-hydroxy-2-oxo-l,2-dihyd ropyridine-3-carboxylic acid

(Cpd 41)

Part 1: Preparation of benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate

Step A: A mixture of butyronitrile (30 mL) and malonyl dichloride (25.0 g, 177 mmol) was stirred at room temperature under N ₂ atmosphere for 3 days. The mixture was diluted with dioxane (100 mL) and the resulting precipitate was filtered, washed with dioxane (20 mL) then ethyl ether (2 X 30 mL), and dried in air to provide intermediate 6-chloro-5- ethyl-4-hydroxypyridin-2(lH)-one (12.7 g, 67% pure, contains 33% of 6-chloro-2-propyl- l,2-dihydropyrimidin-4-ol by-product, based on 1H NMR), which was used directly in the next step.

1H NMR (500 MHz, methanol- d ₄ ) δ ppm, 1.09 - 1.19 (3H, m), 2.72 (2H, q, J=7.36 Hz), 6.43 (1 H, s).

Step B: The pyridinone intermediate (12.7 g) was dissolved in THF (250 mL) followed by the addition of Ph ₃ P (54.0 g, 210 mmol). The mixture was cooled in an ice- water bath and DIAD (42 mL, 211 mmol) was added dropwise. The mixture was stirred for 5 min, followed by the addition of benzyl alcohol (23.6 mL, 228 mmol) dropwise. The cooling bath was removed and the mixture was stirred for 4 hr. Solvent was removed on a rotovap and the residue was treated with 1: 1 hexanes and ethyl ether (600 mL), then stirred for 0.5 hr. The precipitate was filtered and washed with the hexanes-ether mix until no desired product was found in the wash. The filtrates were combined, concentrated and chromatographed (silica gel, ethyl acetate in hexanes 0 - 3 % gradient) to furnish a dibenzylated intermediate, 4,6-bis(benzyloxy)-2-chloro-3-ethylpyridine, as an colorless oil (7.7 g, 12.3% yield over two steps). 1H NMR (500 MHz, CDC1 ₃ ) δ ρρηι 1.08 - 1.19 (3H, m), 2.75 (2H, q, J=7.25 Hz), 5.08 (2H, s), 5.30 - 5.39 (2H, m), 6.27 (1H, s), 7.28 - 7.56 (10 H, m).

Step C: To a solution of the dibenzylated intermediate (7.7 g, 21.8 mmol) in THF (80 mL) at -78 °C was added w-BuLi (21.8 mL, 54.4 mmol) dropwise. The reaction mixture was stirred for an additional 15 min. at -78 °C, then benzyl chloroformate (4.7 mL, 32.6 mmol) was added. The resulting mixture was stirred for 10 min then the cooling bath was removed. The mixture was allowed to warm to room temperature while stirring. The reaction was quenched with an aqueous solution of NH ₄ C1 (5 mL), diluted with ethyl ether (150 mL), then washed with water (2 x 30 mL) and brine (30 mL). After drying with Na ₂ S0 ₄ , the solvent was removed and the residue was chromato graphed (silica gel, ethyl acetate in hexanes, 0 - 5 %) to provide the product as a white crystalline material (6.9 g, yield: 65%).

1H NMR (500 MHz, CDC1 ₃ ) δ ppm 1.10 (3H, t, J=7.41 Hz), 2.66 (2H, q, J=7.57 Hz), 4.97 (2H, s), 5.30 (2H, s), 5.39 (2H, s), 7.24 - 7.43 (15H, m).

Part 2: Preparation of 5-ethyl-6-(5-fluoro-lH-indol-6-yl)-4-hydroxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid

Step A: A mixture of tert-butyl 6-bromo-5-fluoro-lH-indole-l-carboxylate (0.62 g, 2.0 mmol), B ₂ Pin ₂ (0.66 g, 2.6 mmol), PdCLdppf (0.16 g, 0.2 mmol), and KOAc (0.6 g, 6.0 mmol) in dioxane (6.0 mL) was stirred at 88 °C overnight under an Ar atmosphere. The mixture was filtered, evaporated and purified by silica gel chromatography (ethyl acetate in hexanes, 2 to 20% gradient) to give the intermediate tert-butyl 5-fluoro-6-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-indole-l-carboxylate (0.4 g, yield: 56%).

1H NMR (500 MHz, CDC1 ₃ ) δ ppm 8.56 (br. s, 1H), 7.69 (d, J=3.4 Hz, 1H), 7.20 (d, J=9.4 Hz, 1H), 6.54 (dd, J=0.6, 3.4 Hz, 1H), 1.71 (s, 9H), 1.40 (s, 12H).

Step B: A mixture of the carboxylate intermediate (100 mg, 0.28 mmol), Pd ₂ (dba) ₃ (30 mg, 0.033 mmol), i-Bu ₃ PHBF ₄ (19 mg, 0.066 mmol), benzyl 2,4-bis(benzyloxy)-6- chloro-5-ethylnicotinate (160 mg, 0.33 mmol), Cs ₂ C0 ₃ (330 mg, 1.0 mmol) in dioxane (1.0 mL) and H ₂ 0 (0.2 mL) was stirred at 100 °C for 1 hr under an Ar atmosphere, then cooled, treated with water and extracted with ethyl acetate. The organic layer was dried over Na ₂ S0 ₄ , evaporated and purified by silica gel chromatography (ethyl acetate in hexanes 1 to 15% gradient) to give the intermediate tert-butyl 6-(4,6-bis(benzyloxy)-5-

((benzyloxy)carbonyl)-3-ethylpyridin-2-yl)-5-fluoro-lH-in dole-l-carboxylate (0.19 g, yield: 100%). LC-MS 687.4 [M+H] ⁺ , RT 1.75 min.

Step C: The foregoing intermediate was dissolved in diphenyl ether (1.0 mL). The mixture was stirred at 200 °C overnight, then cooled, loaded directly onto a silica gel column and purified with ethyl acetate in hexanes (1 to 20% gradient) to provide the intermediate benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(5-fluoro-lH-indol-6-yl)nicotin ate (0.13 g, yield: 81%). LC-MS 587.3 [M+H] ⁺ , RT 1.57 min. 1H NMR (500 MHz, CDC1 ₃ ) 5 ppm 8.24-8.49 (br. s, 1H), 7.25-7.44 (m, 18H), 6.57 (br. s, 1H), 5.43 (s, 2H), 5.36 (s, 2H), 5.09 (s, 2H), 2.52 (d, J=7.3 Hz, 2H), 0.93 (t, J=7.4 Hz, 3H).

Step D: The nicotinate intermediate (60 mg, 0.1 mmol) was dissolved in a mixture of MeOH (0.5 mL) and ethyl acetate (2.0 mL), then hydrogenated with 10% Pd on charcoal (15 mg) under a balloon of H ₂ for 1 hr at room temperature. The catalyst was filtered over Celite and washed with 10% MeOH in CH ₂ C1 ₂ . The filtrate was concentrated to dryness and the residue triturated with ether, then dried to provide the title compound as pale yellow powder (25 mg, 77% yield).

LC-MS 317.2 [M+H] ⁺ , RT 1.26 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.22 (br. s, 1H), 14.04 (br. s, 1H), 12.89 (br. s, 1H), 11.47 (br. s, 1H), 7.58 (t, J=2.7 Hz, 1H), 7.46-7.54 (m, 2H), 6.54 (t, J=2.0 Hz, 1H), 2.17-2.35 (m, 2H), 0.96 (t, J=7.4 Hz, 3H).

As shown in the table below, additional compounds representative of the present description may be prepared according to Example 1 by substituting the appropriate starting materials, reagents and reaction conditions.

Cpd Data

Ϊ LC-MS 300.2 [M+H] ⁺ , RT 0.80 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.11 (t, J = 7 Hz, 3H), 2.44 (q, J = 7 Hz, 2H), 7.65 (dd, J = 8, 2 Hz, 1H), 7.96-8.00 (m, 2H), 9.21 (s, 1H)

2 LC-MS 301.2 [M+H] ⁺ , RT 0.92 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.37 Hz, 3H), 2.30 (q, J=7.40 Hz, 2H), 7.32 (dd, J=8.20, 1.50 Hz, 1H), 7.69 (dd, J=1.46, 0.67 Hz, 1H), 7.79 (d, J=8.28 Hz, 1H), 8.42 (d, J=3.00 Hz, 1H), 12.52 (br. s, 1H), 12.82 (br. s, 1H), 13.92 (br. s, 1H) Cpd Data

3 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.03 (t, J=7.60 Hz, 3H), 1.80 - 1.94 (m, 2H), 1.96 - 2.07 (m, 2H), 2.30 - 2.39 (m, 2H), 3.06 - 3.20 (m, 2H), 3.43 - 3.49 (m, 2H), 4.48 - 4.58 (m, 2H), 7.17 - 7.22 (m, IH), 7.56 - 7.61 (m, IH), 7.78 - 7.83 (m, IH), 7.93 - 7.99 (m, IH), 11.81 (br. s, IH), 12.77 (br. s, IH), 13.90 (br. s, IH)

4 LC-MS 370.1 [M+H] ⁺ , RT 0.93 min. 1H NMR (500 MHz, DMSO- d ₆ ) δ ppm 1.03 (t, J=7.3 Hz, 3H), 1.30 (t, J=7.1 Hz, 3H), 2.35 (q, J=7.3 Hz, 2H), 2.73 (s, 3H), 3.13 (br. s, 2H), 4.48 (br. s, 2H), 6.80 (m, IH), 7.14 (dd, J=8.2, 1.6 Hz, IH), 7.60 (m, IH), 7.74 (d, J=8.2 Hz, IH), 10.38 (br. s, IH), 11.73 (s, IH), 12.78 (br. s, IH), 13.95 (br. s, IH), 16.33 (br. s, IH)

5 LC-MS 328.0 [M+H] ⁺ , RT 0.89 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.01 (t, J=7.3 Hz, 3H), 2.34 (q, J=7.3 Hz, 2H), 4.24 (br. s, 2H), 6.65 (m, IH), 7.11 (dd, J=8.2, 1.6 Hz, IH), 7.56 (m, IH), 7.70 (d, J=8.2 Hz, IH), 8.47 (br. s, 3H), 11.60 (s, IH), 12.78 (br. s, IH), 13.93 (br. s, IH), 16.34 (br. s, IH)

6 LC-MS 314.0 [M+H] ⁺ , RT 0.84 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.02 (IH, br. s), 14.43 (IH, br. s), 12.55 (IH, br. s), 11.18 (IH, s), 7.47 - 7.61 (m, 2H), 7.16 (d, J=7.57 Hz, IH), 2.52 (s, 3H), 2.29 (br. s, 2H), 0.98 (t, J=7.09 Hz, 3H)

7 LC-MS 368.3 [M+H] ⁺ , RT 0.86 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.82 (t, J=7.4 Hz, 3H), 2.03 - 2.17 (m, IH), 2.22 - 2.33 (m, IH), 2.56 - 2.68 (m, IH), 3.04- 3.26 (m, 3H), 3.34 - 3.49 (m, 4H), 6.96 (d, J=7.3 Hz, IH), 7.17 (dd, J=8.2, 7.3 Hz, IH), 7.48 (dd, J=8.2, 0.9 Hz, IH), 8.99 - 9.16 (m, 2H), 11.46 (s, IH), 12.85 - 12.94 (m, IH), 13.94 (s, IH)

8 LC-MS 382.3 [M+H] ⁺ , RT 0.86 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.82 (t, J=7.6 Hz, 3H), 1.95 - 2.38 (m, 3H), 2.86 (br. s, 3H), 3.01 - 3.34 (m, 4H), 3.48 - 3.71 (m, 3H), 6.98 (d, J=7.6 Hz, IH), 7.19 (dt, J=8.2, 7.6 Hz, IH), 7.49 (d, J=8.2 Hz, IH), 10.15 (br. s, IH), 11.46 (d, J=6.6 Hz, IH), 12.92 (d, J=13.2 Hz, IH), 13.94 (s, IH)

9 LC-MS 311.0 [M+H] ⁺ , RT 1.22 min. 1H NMR (500 MHz, DMSO- d ₆ ) δ ppm 0.00 (m, 2H), 0.48 (m, 2H), 1.58 (m, IH), 6.44 (m, IH), 7.13 (dd, J=8.2, 1.6 Hz, IH), 7.44 (m, IH), 7.52 (m, IH), 7.56 (d, J=8.2 Hz, IH), 11.36 (s, IH), 12.56 (br. s, IH), 13.84 (br. s, IH), 16.23 (br. s, IH) Cpd Data

10 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.03 (t, J=7.40 Hz, 3H), 2.35 (q, J=7.40 Hz, 2H), 2.75 (d, J=4.89 Hz, 6H), 4.44 - 4.52 (m, 2H), 7.17 - 7.24 (m, IH), 7.57 - 7.63 (m, IH), 7.75 - 7.79 (m, IH), 7.91 - 7.98 (m, IH), 9.84 (br. s, IH), 11.85 (br. s, IH), 12.75 (br. s, IH), 13.92 (br. s, IH)

11 LC-MS 330.3 [M+H] ⁺ , RT 1.26 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.12 (t, J = 7 Hz, 3H), 2.48 (q, J = 7 Hz, 2H), 3.25 (s, 3H), 3.73 (br. s, 2H), 3.91 (br. s, 2H), 6.61 (d, J = 8 Hz, IH), 7.03-7.06 (m, IH), 7.20 (d, J = 8 Hz, IH)

12 LC-MS 394.4 [M-H] ^~ , RT 0.90 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.6 Hz, 3H), 1.74 - 2.43 (m, 6 H), 2.68-2.93 (m, 5H), 7.08 - 7.15 (m, IH), 7.50 - 7.61 (m, IH), 7.61 - 7.77 (m, IH), 10.31 (s, IH), 11.31 (s, IH), 12.78 (s, IH), 13.90 (s, IH)

13 LC-MS 317.3 [M+H] ⁺ , RT 1.13 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.10 (t, J = 7 Hz, 3H), 2.48 (q, J = 7 Hz, 2H), 3.41 (t, J = 5 Hz, 2H), 4.26 (t, J = 5 Hz, 2H), 6.63 (dd, J = 8, 2 Hz, IH), 6.68 (d, J = 2 Hz, IH), 6.82 (dd, J = 8, 2 Hz, IH)

14 LC-MS 370.3 [M+H] ⁺ , RT 0.90 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.02 (t, J=7.3 Hz, 3H), 2.35 (q, J=7.3 Hz, 2H), 2.37 (s, 3H), 2.76 (br. s, 6H), 4.44 (br. s, 2H), 7.13 (dd, J=8.3, 1.4 Hz, IH), 7.55 (m, IH), 7.70 (d, J=8.4 Hz, IH), 10.40 (br. s, IH), 11.35 (s, IH), 12.73 (br. s, IH), 13.97 (br. s, IH), 16.40 (br. s, IH)

15 LC-MS 384.3 [M+H] ⁺ , RT 0.91 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.02 (t, J=7.3 Hz, 3H), 1.37 (t, J=7.3 Hz, 3H), 2.35 (q, J=7.3 Hz, 2H), 2.37 (s, 3H), 2.68 (br. s, 3H), 3.14 (br. s, 2H), 4.43 (br. s, 2H), 7.12 (dd, J=8.3, 1.4 Hz, IH), 7.54 (m, IH), 7.69 (d, J=8.4 Hz, IH), 10.14 (br. s, IH), 11.37 (s, IH), 12.74 (br. s, IH), 14.02 (br. s, IH), 16.40 (br. s, IH)

16 LC-MS 333.3 [M+H] ⁺ , RT 1.24 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.11 (t, J = 7 Hz, 3H), 2.48 (q, J = 7 Hz, 2H), 3.11-3.13 (m, 2H), 3.65-3.67 (m, 2H), 6.66-6.69 (m, 2H), 7.11 (d, J = 8 Hz, IH)

17 LC-MS 368.4 [M+H] ⁺ , RT 0.87 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.6 Hz, 3H), 1.95 - 2.06 (m, 2H), 2.28 - 2.37 (q, J=7.6 Hz, 2H), 2.92 - 3.03 (m, 2H), 3.49 - 3.55 (m, 2H), 4.42 (s, 2H), 7.05 - 7.14 (m, IH), 7.50 (s, 2H), 7.60 - 7.71 (m, 2H), 9.06 (s, 2H), 11.47 (s, IH), 12.80 (s, IH), 13.89 (s, IH) Cpd Data

18 LC-MS 382.4 [M+H] ⁺ , RT 0.88 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.6 Hz, 3H), 1.80 - 2.22 (m, 2H), 2.26 - 2.44 (m, 2H), 2.64 - 3.12 (m, 5H), 3.48 - 3.85 (m, 2H), 4.44 - 4.75 (m, 2H), 7.06 - 7.17 (m, IH), 7.44 - 7.55 (m, IH), 7.60 - 7.80 (m, IH), 10.29 (s, IH), 11.45 (s, IH), 12.78 (s, IH), 13.90 (s, IH)

20 LC-MS 324.1 [M+H] ⁺ , RT 1.15 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.37 Hz, 3H), 2.30 (q, J=7.40 Hz, 2H), 7.32 (dd, J=8.20, 1.50 Hz, IH), 7.69 (dd, J=1.46, 0.67 Hz, IH), 7.79 (d, J=8.28 Hz, IH), 8.42 (d, J=3.00 Hz, IH), 12.52 (br. s, IH), 12.82 (br. s, IH), 13.92 (br. s, IH)

21 LC-MS 316.3 [M+H] ⁺ , RT 1.15 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.06 (t, J = 7 Hz, 3H), 2.44 (q, J = 7 Hz, 2H), 3.53-3.55 (m, 2H), 3.71-3.73 (m, 2H), 6.73-6.76 (m, IH), 6.81-6.83 (m, 2H)

29 LC-MS 388.3 [M-H] ^~ , RT 1.12 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.29 (br. s, IH), 13.94 (s, IH), 12.83 (br. s, IH), 12.07 (s, IH), 10.46 (br. s, IH), 7.68- 7.73 (m, 2H), 7.27 (d, J=9.8 Hz, IH), 4.53 (s, 2H), 2.84 (s, 6H), 2.33 (q, J=7.3 Hz, 2H), 1.01 (t, J=7.3 Hz, 3H)

30 LC-MS 356.4 [M+H] ⁺ , RT 0.90 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.50 (br. s, IH), 13.90 (s, IH), 12.80 (br. s, IH), 11.70 (s, IH), 10.06 (br. s, IH), 7.74 (s, IH), 7.60 (d, J=8.51 Hz, IH), 7.25 (dd, J=8.35, 1.42 Hz, IH), 6.78 (s, IH), 4.47 (s, 2H), 2.80 (s, 6H), 2.33 (q, J=7.25 Hz, 2H), 1.00 (t, J=7.41 Hz, 3H)

31 LC-MS 382.4 [M+H] ⁺ , RT 0.92 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.34 (br. s, IH), 13.90 (s, IH), 12.75 (br. s, IH), 11.66 (s, IH), 10.11 (br. s, IH), 7.73 (s, IH), 7.60 (d, J=8.5 Hz, IH), 7.25 (dd, J=8.5, 1.6 Hz, IH), 6.78 (d, J=1.3 Hz, IH), 4.55 (s, 2H), 3.47 (br. s, 2H), 3.21 (br. s, 2H), 2.33 (q, J=7.3 Hz, 2H), 2.04 (br. s, 2H), 1.88 (br. s, 2H), 1.00 (t, J=7.4 Hz, 3H)

36 LC-MS 368.3 [M-H] ^~ , RT 0.92 min. 1H NMR (500 MHz, DMSO- ₆ ): δ 13.91 (IH, s), 12.75 (IH, s) 11.38 (IH, s), 10.15 (br. s, IH), 7.79 (IH, d, J = 8.5 Hz), 7.51 (IH, s), 7.45 (IH, d, J = 2.5 Hz), 7.12 (IH, dd, J = 8.5 Hz, 1.5 Hz), 3.35 (2H, q, J = 7 Hz), 3.17 (2H, m), 2.86 (6H, s), 2.37 (2H, m), 1.03 (3H, t, J = 7 Hz) Cpd Data

37 LC-MS 329.3 [M+H] ⁺ , RT 0.94 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 14.19- 14.59 (br. s, IH), 11.28-11.37 (br. s, IH), 7.64 (d, J=8.2 Hz, IH), 7.48 (s, 1H), 7.13 (dd, J=8.2, 1.3 Hz, IH), 3.92 (s, 2H), 2.42 (s, 6H), 2.34 (q, J=7.2 Hz, 2H), 1.03 (t, J=7.2 Hz, 3H)

38 LC-MS 360.4 [M+H] ⁺ , RT 0.92 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 13.98 (br. s, IH), 12.89 (br. s, IH), 11.51 (s, IH), 9.09 (br. s, 2H), 7.79 (d, J=8.2 Hz, IH), 7.68 (s, IH), 7.25 (d, J=7.9 Hz, IH), 4.44 (br. s, 2H), 2.71 (s, 3H), 2.37 (q, J=7.1 Hz, 2H), 1.06 (t, J=7.3 Hz, 3H)

42 LC-MS 356.2 [M+H] ⁺ , RT 0.96 min. 1H NMR (500 MHz, methanol- d ₄ ) δ ppm 1.10 (t, J = 7 Hz, 3H), 1.83 (d, J = 6 Hz, 3H), 2.48 (q, J = 7 Hz, 2H), 2.67 (s, 3H), 4.65 (br. s, IH), 6.76-6.78 (m, IH), 7.13-7.18 (m, IH), 7.58 (br. s, IH), 7.74-7.77 (m, IH)

43 LC-MS 368.2 [M-H] ⁺ , RT 0.99 min. 1H NMR (500 MHz, methanol-^) δ ppm 1.05 (t, J = 7 Hz, 3H), 1.73 (d, J = 6 Hz, 3H), 2.40 (q, J = 7 Hz, 2H), 2.78 (bs, 6H), 4.65 (bs, IH), 6.80 (s, IH), 7.14 (d, J = 8 Hz IH), 7.61 (s, IH), 7.74 (d, J = 8 Hz IH)

44 LC-MS 347.1 [M+H] ⁺ , RT 0.93 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 14.01 (br. s, IH), 12.84 (br. s, IH), 7.12 (d, J=5.7 Hz, IH), 6.80 (br. s, IH), 3.61 (t, J=8.2 Hz, 2H), 3.49 (s, 3H), 3.42-3.48 (m, 2H), 3.03-3.16 (m, 2H), 2.65 (t, J=7.1 Hz, 2H)

45 LC-MS 331.0 [M+H] ⁺ , RT 1.29 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.26 (br. s, IH), 13.94 (s, IH), 12.93 (br. s, IH), 7.66 (d, J=6.9 Hz, IH), 7.56 (d, J=11.0 Hz, IH), 7.47 (d, J=3.2 Hz, IH), 6.56 (d, J=2.8 Hz, IH), 3.83 (s, 3H), 2.15-2.36 (m, 2H), 0.93 (t, J=7.3 Hz, 3H)

46 LC-MS 317.0 [M+H] ⁺ , RT 1.20 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.28 (br. s, IH), 13.94 (s, IH), 12.90 (br. s, IH), 11.46 (br. s, IH), 7.66 (d, J=6.9 Hz, IH), 7.48 (t, J=2.7 Hz, IH), 7.38 (d, J=10.7 Hz, IH), 6.56 (br. s, IH), 2.16-2.38 (m, 2H), 0.94 (t, J=7.4 Hz, 3H)

47 LC-MS 319.2 [M+H] ⁺ , RT 1.54 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 13.89 (br. s, IH), 12.72 (s, IH), 7.05 (d, J=7.3 Hz, IH), 6.40 (d, J=11.3 Hz, IH), 3.57 (t, J=8.7 Hz, 2H), 2.96 (t, J=8.7 Hz, 2H), 2.30 (q, J=6.8 Hz, 2H), 0.96 (t, J=7.4 Hz, 3H) Cpd Data

48 LC-MS 333.0 [M+H] ⁺ , RT 1.34 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 13.89 (s, 1H), 12.73 (s, 1H), 7.04 (d, J=7.3 Hz, 1H), 6.49 (d, J=11.7 Hz, 1H), 3.46 (t, J=8.5 Hz, 2H), 2.93 (t, J=8.4 Hz, 2H), 2.80 (s, 3H), 2.30 (q, J=7.6 Hz, 2H), 0.96 (t, J=7.3 Hz, 3H)

49 LC-MS 285.1 [M+H] ⁺ , RT 1.17 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.50 (br. s, 1H), 13.96 (br. s, 1H), 12.91 (br. s, 1H), 11.17 (br. s, 1H), 7.68-7.80 (m, 1H), 7.43 (t, J=2.8 Hz, 1H), 7.10-7.19 (m, 2H), 6.57 (dd, J=3.2, 1.9 Hz, 1H), 1.74 (s, 3H);

50 LC-MS 299.1 [M+H] ⁺ , RT 1.24 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.28 (br. s, 1H), 14.03 (br. s, 1H), 12.90 (br. s, 1H), 11.22 (br. s, 1H), 7.72 (dd, J=6.9, 1.9 Hz, 1H), 7.42 (t, J=2.8 Hz, 1H), 7.08-7.19 (m, 2H), 6.56 (dd, J=3.0, 1.7 Hz, 1H), 2.30 (br. s, 1H), 2.05 (br. s, 1H), 0.85 (t, J=7.4 Hz, 3H)

51 LC-MS 299.1 [M+H] ⁺ , RT 1.22 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.19 (br. s, 1H), 13.95 (br. s, 1H), 13.06 (br. s, 1H), 7.74 (dd, J=7.9, 1.3 Hz, 1H), 7.38 (d, J=2.8 Hz, 1H), 7.15 (dd, J=7.9, 7.3 Hz, 1H), 7.07 (dd, J=7.3, 1.3 Hz, 1H), 6.57 (d, J=3.2 Hz, 1H), 3.45 (s, 3H), 1.70 (s, 3H)

52 LC-MS 313.2 [M+H] ⁺ , RT 1.29 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.24 (br. s, 1H), 13.97 (br. s, 1H), 13.05 (br. s, 1H), 7.74 (dd, J=7.7, 1.1 Hz, 1H), 7.38 (d, J=3.2 Hz, 1H), 7.15 (t, J=1.0 Hz, 1H), 7.09 (dd, J=1.0 Hz, 1H), 6.56 (d, J=3.2 Hz, 1H), 3.46 (s, 3H), 2.25-2.36 (m, 1H), 1.94-2.05 (m, 1H), 0.85 (t, J=7.4 Hz, 3H)

Example 2

6-{2-[2-(Dimethylamino)ethyl]-lH-indol-6-yl}-5-ethyl-4-hy droxy-2-oxo-l,2- dihydropyridine-3-carboxylic acid (Cpd 34)

Step A: A mixture of (lH-indol-6-yl)boronic acid (1.18 g, 7.35 mmol), benzyl 2,4- bis(benzyloxy)-6-chloro-5-ethylnicotinate (prepared according to Example 1, Part 1) (3.9 g, 8.1 mmol), tris(dibenzylideneacetone)-dipalladium (340 mg, 0.37 mmol), tri-tert- butylphosphonium tetrafluoroborate (215 mg, 0.74 mmol), CS ₂ CO ₃ (7.2 g, 22.1 mmol), H ₂ 0 (6 mL) and dioxane (15 mL) was stirred under argon at 80 °C for 2 hrs. The reaction mixture was partitioned between EtOAc (50 mL) and aqueous saturated NaHC0 ₃ (50 mL). The organic layer was concentrated and chromatographed on silica gel, eluting with 0-20% EtOAc in hexanes to yield the intermediate benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(lH-indol-6- yl)nicotinate (3.9 g) as a brown foam.

1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.96 (t, J=7.40 Hz, 3H), 2.58 (q, J=7.40 Hz, 2H), 5.04 (s, 2H), 5.36 (s, 2H), 5.38 (s, 2H), 6.47 - 6.50 (m, 1H), 7.08 - 7.12 (m, 1H), 7.28 - 7.44 (m, 16H), 7.48 - 7.50 (m, 1H), 7.59 - 7.63 (m, 1H), 11.22 (br. s, 1H).

Step B: A mixture of the intermediate (160 mg, 0.28 mmol), (2-bromoethoxy)(tert- butyl)dimethylsilane (120 μΐ,, 0.56 mmol), K ₂ C0 ₃ (80 mg, 0.56 mmol),

bis(acetonitrile)dichloropalladium (7 mg, 0.03 mmol), norbornene (53 mg, 0.56 mmol), dimethylacetamide (1.4 mL) and H ₂ 0 (0.2 mL) was stirred under Ar at 70 °C for 16 hrs. The reaction mixture was partitioned between H ₂ 0 (20 mL) and EtOAc (20 mL). The organic layer was separated, dried over Na ₂ S0 ₄ , then filtered and concentrated. The crude residue was chromatographed on silica gel, eluting with 10% EtOAc in hexanes to afford the intermediate benzyl 2,4-bis(benzyloxy)-6-(2-(2-((tert-butyldimethylsilyl)oxy)eth yl)- 1H- indol-6-yl)-5-ethylnicotinate (132 mg, 65%).

1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.02 (s, 6H), 0.85 (s, 9H), 0.96 (t, J=7.40 Hz, 3H), 2.58 (q, J=7.40 Hz, 2H), 2.93 (t, J=7.20 Hz, 2H), 3.90 (t, J=7.20 Hz, 2H), 5.02 (s, 2H), 5.36 (s, 2H), 5.38 (s, 2H), 6.23 - 6.26 (m, 1H), 7.03 - 7.07 (m, 1H), 7.29 - 7.43 (m, 16H), 7.46 - 7.50 (m, 1H).

Step C: To a solution of the intermediate (220 mg, 0.3 mmol) in THF (10 mL) was added TBAF (400 μΐ,, 1M in THF, 0.4 mmol). The mixture was stirred at 25 °C for 1.5 hrs, then concentrated and the crude residue was chromatographed on silica gel, eluting with 50% EtOAc in hexanes to afford the intermediate benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(2-(2- ((methylsulfonyl)oxy)ethyl)- lH-indol-6-yl)nicotinate (150 mg, 77%).

1H NMR (500 MHz, CDC1 ₃ ) δ ppm 1.03 (t, J=7.37 Hz, 3H), 2.64 (q, J=7.41 Hz, 2H), 3.03 (t, J=5.71 Hz, 2H), 3.98 (t, J=5.71 Hz, 2H), 5.06 (s, 2H), 5.35 (s, 2H), 5.45 (s, 2H), 6.33 (d, J=1.02 Hz, 1H), 7.18 (dd, J=8.12, 1.50 Hz, 1H), 7.27 - 7.42 (m, 16H), 7.58 (d, J=8.12 Hz, 1H), 8.61 (br. s, 1H).

Step D: To a solution of the intermediate (160 mg, 0.26 mmol) in CH ₂ C1 ₂ (3 mL), cooled to 0 °C, was added N,N-diisopropylethylamine (50 μί, 0.26 mmol) and MsCl (22 μί, 0.26 mmol). The reaction mixture was stirred for 1 hr at 0 °C and then concentrated. The crude residue was dissolved in CH CN (2 mL) and dimethylamine (1.3 mL, 2M in THF, 2.6 mmol) was added. After stirring for 2 hrs at 50 °C, the reaction mixture was concentrated. The crude residue, 10% Pd/C (8 mg), MeOH (1 mL) and 3 M HC1 in MeOH (5 drops) was stirred under H ₂ (1 atm) for 1 hr. The mixture was passed through a 0.3 μιη HPLC filter and concentrated. The crude residue was triturated with Et ₂ 0 to afford 12 mg (15% over 3 steps) of product.

LC-MS: 370.1 [M+H] ⁺ , RT 0.55 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.02 (t, J=7.40 Hz, 3H), 2.35 (q, J=7.40 Hz, 2H), 2.82 (s, 6H), 3.21 - 3.28 (m, 2H), 3.41 - 3.49 (m, 2H), 6.37 - 6.41 (m, 1H), 7.02 - 7.07 (m, 1H), 7.44 - 7.47 (m, 1H), 7.57 - 7.63 (m, 1H), 11.61 (br. s, 1H), 12.73 (br. s, 1H), 13.90 (br. s, 1H).

As shown in the table below, additional compounds representative of the present description may be prepared according to Example 2 by substituting the appropriate starting materials, reagents and reaction conditions.

Cpd Data

~L9 LC-MS 355.0 [M-H] ^~ , 357.0 [M+H] ⁺ , RT 1.18 min. ^l H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.99 (t, J=7.36 Hz, 3H), 2.34 (q, J=7.36 Hz, 2H), 2.95 (t, J=6.78 Hz, 2H), 3.74 (s, 3H), 3.71 - 3.78 (m, 2H), 4.84 (t, J=5.04 Hz, 1H), 6.36 (s, 1H), 7.14 (dd, J=8.35, 1.73 Hz, 1H), 7.51 - 7.68 (m, 2H), 12.70 (br. s, 1H), 14.22 (br. s, 1H), 16.20 (br. s, 1H)

22 LC-MS 384.1 [M+H] ⁺ , RT 0.96 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.95 (t, J=7.41 Hz, 3H), 2.28 (d, J=6.94 Hz, 2H), 2.33 (s, 6H), 2.72 (t, J=7.57 Hz, 2H), 2.96 (t, J=7.72 Hz, 2H), 3.72 (s, 3H), 6.31 (s, 1H), 7.08 (dd, J=8.51, 1.58 Hz, 1H), 7.36 - 7.54 (m, 2H)

23 LC-MS 408.4 [M-H] ^~ , 410.4 [M+H] ⁺ , RT 0.89 min. 1H NMR (500 MHz, DMSO- ₆ ) 5 ppm 1.00 (t, J=7.41 Hz, 3H), 1.92 (br. s, 2H), 2.05 (br. s, 2H), 2.34 (q, J=7.41 Hz, 2H), 3.10 (br. s, 2H), 3.20 - 3.31 (m, 2H), 3.47 - 3.58 (m, 2H), 3.62 (br. s, 2H), 3.80 (s, 3H), 6.47 (s, 1H), 7.21 (dd, J=8.51, 1.89 Hz, 1H), 7.59 - 7.79 (m, 2H), 10.68 (br. s, 1H), 12.74 (br. s, 1H), 13.91 (s, 1H)

24 LC-MS 354.5 [M-H] ^~ , 356.3 [M+H] ⁺ , RT 0.86 min. 1H NMR (500 MHz, DMSO- ₆ ) 5 ppm 0.98 (t, J=7.41 Hz, 3H), 2.33 (q, J=7.46 Hz, 2H), 3.10 - 3.29 (m, 4H), 3.77 (s, 3H), 6.47 (s, 1H), 7.09 - 7.31 (m, 1H), 7.51 - 7.69 (m, 2H), 8.10 (br. s, 3H), 12.74 (s, 1H), 13.90 (s, 1H) Cpd Data

^~ 27 LC-MS 368.4 [M-H] ^~ , 370.4 [M+H] ⁺ , RT 0.87 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.98 (t, J=7.25 Hz, 3H), 2.33 (q, J=7.25 Hz, 2H), 2.62 (t, J=5.04 Hz, 3H), 3.15 - 3.40 (m, 4H), 3.77 (s, 3H), 6.46 (s, 1H), 7.20 (d, J=8.20 Hz, 1H), 7.53 - 7.62 (m, 2H), 8.85 (br. s, 2H), 12.74 (s, 1H), 13.90 (br. s, 1H)

28 LC-MS 384.4 [M+H] ⁺ , RT 0.88 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.98 (t, J=7.25 Hz, 3H), 1.23 (t, J=6.94 Hz, 3H), 2.33 (q, J=7.25 Hz, 2H), 3.02 (br. s, 2H), 3.15 - 3.40 (m, 4H), 3.78 (s, 3H), 6.47 (s, 1H), 7.19 (d, J=8.51 Hz, 1H), 7.44 - 7.66 (m, 2H), 8.99 (br. s, 2H), 12.74 (br. s, 1H), 13.90 (br. s, 1H)

32 LC-MS 342.3 [M+H] ⁺ , RT 0.53 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.01 (t, J=7.13 Hz, 3H), 2.35 (q, J=7.40 Hz, 2H), 3.10 - 3.24 (m, 4H), 6.38 (s, 1H), 6.99 -

7.08 (m, 1H), 7.43 (s, 1H), 7.55 - 7.63 (m, 1H), 8.27 (br. s, 2H), 11.64 (br. s, 1H), 12.73 (br. s, 1H), 13.90 (br. s, 1H)

33 LC-MS 382.4 [M-H] ^~ , RT 0.92 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 0.93 (t, J=7.57 Hz, 3H), 0.98 (t, J=7.41 Hz, 3H), 1.70 (dd, J=15.45, 7.57 Hz, 2H), 2.33 (q, J=7.57 Hz, 2H), 2.98 (br. s, 2H), 3.86 (s, 3H), 4.45 (br. s, 2H), 6.81 (s, 1H), 7.29 (d, J=8.51 Hz, 1H), 7.67 (d, J=8.51 Hz, 1H), 7.74 (s, 1H), 9.12 (br. s, 2H), 12.79 (s, 1H), 13.90 (s, 1H)

35 LC-MS 396.3 [M+H] ⁺ , RT 0.55 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.02 (t, J=7.40 Hz, 3H), 1.85 - 1.92 (m, 2H), 1.98 - 2.07 (m, 2H), 2.35 (q, J=7.40 Hz, 2H), 3.03 - 3.13 (m, 2H), 3.18 - 3.25 (m, 2H), 3.47 - 3.63 (m, 4H), 6.41 (s, 1H), 7.03 -

7.09 (m, 1H), 7.46 (s, 1H), 7.58 - 7.63 (m, 1H), 11.51 (br. s, 1H), 12.72 (br. s, 1H), 13.90 (br. s, 1H)

Example 3

6-{2-[(Dimethylamino)methyl]-3-(trifluoromethyl)-lH-indol-6- yl}-5-ethyl-4-hydroxy-2-oxo- l,2-dihydropyridine-3-carboxylic acid (Cpd 25)

Step A: Trifluoroiodomethane was bubbled for 2 min into a mixture of benzyl 2,4- bis(benzyloxy)-5-ethyl-6-(2-formyl- lH-indol-6-yl)nicotinate (prepared using the procedure from Example 1, part 2, step B) (240 mg, 0.4 mmol) and tris(bipyridine)ruthenium(II) chloride hexahydrate (9 mg, 0.012 mmol) in CH ₃ CN (1.6 mL). The solution was stirred at room temperature for 3 hrs under a 26 W flourescent household bulb (3" from vial). The mixture was partitioned between EtOAc (20 mL) and H ₂ 0 (20 mL). The organic layer was washed with brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromato graphed on silica gel, eluting with 0-40% EtOAc in hexanes to yield the intermediate benzyl 2,4-bis(benzyloxy)-5-ethyl-6-(2-formyl-3-(trifluoromethyl)- lH-indol-6- yl)nicotinate 66 mg of white powder (25%).

LC-MS: 665.8 [M+H] ⁺ , RT 1.84 min. 1H NMR (500 MHz, acetone- ₆ ) δ ppm 1.04 (t, J=7.3 Hz, 3H), 2.63 (q, J=7.3 Hz, 2H), 5.13 (s, 2H), 5.42 (s, 2H), 5.43 (s, 2H), 7.29-7.48 (15H), 7.50 (dd, J=8.5, 1.3 Hz, 1H), 7.83 (m, 1H), 7.95 (m, 1H), 10.23 (s, 1H), 11.86 (br. s, 1H).

Step B: To a mixture of the intermediate (35 mg, 0.05 mmol), acetic acid (6 μί, 0.10 mmol), triethylamine (14 μΕ, 0.10 mmol) and dimethylamine hydrochloride (8 mg, 0.10 mmol) in 1,2-dichloroethane (1 mL) was added sodium triacetoxyborohydride (22 mg, 0.10 mmol). The mixture was stirred at room temperature for 1 hr and partitioned between CH ₂ C1 ₂ (4 mL) and aqueous 1 M K ₂ C0 ₃ (4 mL). The organic layer was loaded directly onto silica gel, eluting with 3-6% MeOH in CH ₂ C1 ₂ to yield the intermediate benzyl 2,4- bis(benzyloxy)-6-(2-((dimethylamino)methyl)-3-(trifluorometh yl)-lH-indol-6-yl)-5- ethylnicotinate (20 mg, 58%).

LC-MS: 694.8 [M+H] ⁺ , RT 1.33 min.

Step C: A mixture of the intermediate (20 mg, 0.03 mmol), 10% Pd/C (5 mg), MeOH (1 mL) and 3 M HC1 in MeOH (5 drops) was stirred under H ₂ (1 atm) for 1 hr. The mixture was passed through a 0.3 μιη HPLC filter and concentrated, yielding the title compound (12 mg, 100%) as a white powder.

LC-MS: 424.4 [M+H] ⁺ , RT 0.94 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.02 (t, J=7.3 Hz, 3H), 2.33 (q, J=7.3 Hz, 2H), 2.85 (br. s, 6H), 4.62 (br. s, 2H), 7.34 (dd, J=8.3, 1.4 Hz, 1H), 7.78 (s, 1H), 7.81 (d, J=8.4 Hz, 1H), 10.49 (br. s, 1H), 12.65 (s, 1H), 12.85 (br. s, 1H), 13.93 (s, 1H), 16.28 (br. s, 1H).

As shown in the table below, additional compounds representative of the present description may be prepared according to Example 3 by substituting the appropriate starting materials, reagents and reaction conditions.

Cpd Data

26 LC-MS 424.4 [M+H] ⁺ , RT 0.95 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 1.00 (t, J=7.3 Hz, 3H), 1.27 (t, J=7.3 Hz, 3H), 2.32 (q, J=7.3 Hz, 2H), 3.10 (q, J=7.3 Hz, Cpd Data

2H), 4.49 (s, 2H), 7.32 (dd, J=8.3, 1.4 Hz, 1H), 7.76 (s, 1H), 7.78 (d, J=8.4 Hz, 1H), 9.39 (br. s, 2H), 12.63 (s, 1H), 12.85 (br. s, 1H), 13.93 (s, 1H), 16.30 (br. s, 1H)

Example 4

5-Ethyl-4-hydroxy-6-[3-methyl-2-(N-methylglycyl)-lH-indol-6- yl]-2-oxo-l,2- dihydropyridine-3-carboxylic acid (Cpd 39)

Step A: A mixture of benzyl 6-(2-acetyl-3-methyl-lH-indol-6-yl)-2,4-bis(benzyloxy)- 5-ethylnicotinate (prepared according to the procedure from Example 1, part 2, step B) (0.1 g, 0.16 mmol), Boc ₂ 0 (38 mg, 0.18 mmol) and a catalytic amount of DMAP in CH ₂ C1 ₂ (2.0 mL) was stirred at room temperature overnight and then evaporated. The residue was purified by silica gel column chromatography with EtOAc in hexanes (2 to 25% gradient) to yield the intermediate tert-butyl 2-acetyl-6-(4,6-bis(benzyloxy)-5-((benzyloxy)carbonyl)-3- ethylpyridin-2-yl)-3-methyl-lH-indole-l-carboxylate (90 mg, 78%).

LC-MS 735.9, [M+H] ⁺ , RT 1.86 min.

Step B: Into a mixture of the intermediate (83 mg, 0.11 mmol) and DIPEA (71 mg, 0.55 mmol) in CH ₂ C1 ₂ (1.0 mL) cooled at 0 °C was added TMSOTf (98 mg, 0.44 mmol). The mixture was stirred at 0 °C for 1 hr and then quenched with saturated sodium bicarbonate followed by extraction with ether (3x). The organic layer was combined, dried and evaporated. To the residue was added THF (1.5 mL) and solid sodium bicarbonate (28 mg). The mixture was cooled to 0 °C and NBS (20 mg, 0.11 mmol) was added. Water was added after 1 hr and the mixture was extracted with ether (3x). The ether layers were combined, then washed with dilute HC1 and brine and the solvent was evaporated. Methylamine in methanol (1.0 mL, 7.0 mmol, 7.0 M) was added to the residue, then after 10 min, the mixture was evaporated. The residue was purified by silica gel column chromatography with MeOH in CH ₂ C1 ₂ (0 to 10% gradient) to give the intermediate tert-butyl 6-(4,6-bis(benzyloxy)-5- ((benzyloxy)carbonyl)-3-ethylpyridin-2-yl)-3-methyl-2-(methy lglycyl)-lH-indole-l- carboxylate (24 mg, 28%).

LC-MS 755.0, [M+H] ⁺ , RT 1.83 min.

Step C: A solution of the intermediate (24 mg, 0.032 mmol) in TFA (1.0 mL) was stirred at 60 °C for 30 min. The organic volatiles were removed by a stream of N ₂ and the residue was treated with 1 N HC1 in ether. The mixture was stirred for 15 min at room temperature and then filtered. The solid was washed with ether (2x) to give the title compound (12 mg, 89%) as an HC1 salt.

LC-MS 382.4, [M+H] ⁺ , RT 0.90 min. 1H NMR (500 MHz, methanol-^) δ ppm 7.96 (d, J=8.5 Hz, IH), 7.59 (s, IH), 7.23 (d, J=8.2 Hz, IH), 4.70 (br. s, 2H), 2.90 (s, 3H), 2.74 (s, 3H), 2.47 (q, J=7.3 Hz, 2H), 1.12 (t, J=7.4 Hz, 3H).

As shown in the table below, additional compounds representative of the present description may be prepared according to Example 4 by substituting the appropriate starting materials, reagents and reaction conditions.

Cpd Data

₄₀ LC-MS 398.3, [M+H] ⁺ , RT 1.02 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 16.08- 16.30 (br. s, IH), 13.73-13.90 (br. s, IH), 12.69-12.87 (br. s, IH), 9.81-9.99 (br. s, IH), 7.88 (d, J=8.6 Hz, IH), 7.49 (s, IH), 7.12 (d, J=8.6 Hz, IH), 4.78-4.88 (br. s, 2H), 2.88 (s, 6H), 2.59 (s, 3H), 2.24 (q, J=7.2 Hz, 2H), 0.95 (t, J=7.2 Hz, 3H)

Example 5

5-Amino-4-hydroxy-6-(l-methyl-lH-indol-5-yl)-2-oxo-l,2-dihyd ropyridine-3-carboxylic acid (Cpd 53)

Step A: To a solution of 3-(benzyloxy)-2,4-dichloropyridine (2.55 g, 9 mmol) in THF (40 mL) was added LDA (4.2 mL, 10.6 mmol) at -78 °C. After 30 min, iodine (2.97g, 11.7 mmol) was added and the mixture was stirred at room temperature for 2.5 hrs. The mixture was quenched with saturated NH ₄ C1, extracted with EtOAc, washed with Na ₂ S ₂ 0 ₃ , water and brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromatographed over silica gel with CH ₂ C1 ₂ in hexanes (0-40%) to give the intermediate 3-(benzyloxy)-2,4- dichloro-5-iodopyridine (2.8 g, 76%).

Step B: To a solution of benzyl alcohol (1.56 mL, 15.1 mmol) in THF (20 mL) was added NaH (604 mg, 15.1 mmol, 60% in mineral oil) at 0 °C. The intermediate (2.80 g, 6.86 mmol) in THF (10 mL) was added after 5 min. The reaction mixture was stirred at room temperature for 2 hrs, quenched with saturated NH ₄ C1, extracted with ether, washed with water and brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromatographed from silica gel with EtOAc in hexanes (0-10%) to give the intermediate 2,3,4-tris(benzyloxy)-5-iodopyridine (3.205 g, 84%) as a clear oil, which solidified upon standing. LC-MS 552.2 [M+H] ⁺ , RT 1.69 min.

Step C: To a solution of the intermediate (1.102 g, 2.0 mmol) in THF (5 mL) was added i-PrMgCl«LiCl (3.1 mL, 4.0 mmol, 1.3 M in THF) at -45 °C. After 30 min, the solution was cooled to -78 °C, then cannulated to a solution of 2,4,6- triisopropylbenzenesulfonyl azide (1.856 g, 6.0 mmol) in THF (5 mL) at -78 °C. The mixture was warmed to rt, quenched with saturated NH ₄ C1, extracted with ether, washed with water and brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromatographed from silica gel with EtOAc in hexanes (0-8%) to give the intermediate 5- azido-2,3,4-tris(benzyloxy)pyridine (0.75 g, 80%) as a clear oil.

LC-MS 467.2 [M+H] ⁺ , RT 1.72 min. 1H NMR (500 MHz, CDC1 ₃ ) δ ppm 5.12 (s, 2H), 5.28 (s, 2H), 5.38 (s, 2H,) 7.26 - 7.40 (m, 15H), 7.93 (s, 1H).

Step D: To a solution of the intermediate (716 mg, 1.53 mmol) in EtOH (15 mL) and THF (7.5 mL) were added zinc (201 mg, 3.07 mmol) and FeCl ₃ «6H ₂ 0 (829 mg, 3.07 mmol). The mixture was refluxed for 1 hr. The mixture was cooled to room temperature, extracted with EtOAc, washed with saturated NaHC0 ₃ , water and brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromatographed over silica gel with EtOAc in hexanes (0-30%) to give the intermediate 4,5,6-tris(benzyloxy)pyridin-3-amine (0.57 g, 84%) as a yellow oil, which solidified upon standing.

LC-MS 441.1 [M+H] ⁺ , RT 1.48 min. Step E: To a solution of the intermediate (224 mg, 0.51 mmol) in DMF (2.6 mL) was added NBS (92 mg, 0.51 mmol) at room temperature. The reaction mixture was quenched after 10 min with saturated 10% Na ₂ C0 ₃ , extracted with EtOAc, washed with water and brine, dried over Na ₂ S0 ₄ , then filtered and concentrated. The residue was chromatographed from silica gel with EtOAc in hexanes (0-10%) to give the intermediate 4,5,6- tris(benzyloxy)-2-bromopyridin-3-amine (0.226 g, 85%) as a light yellow oil.

LC-MS 521.2 [M+H] ⁺ , RT 1.62 min.

Step F: To a mixture of the intermediate (243 mg, 0.467 mmol), ( 1 -methyl- lH-indol- 6-yl)boronic acid (163 mg, 0.93 mmol), Pd ₂ dba ₃ (42 mg, 0.05 mmol) and t-Bu ₃ PHBF ₄ (28 mg, 0.09 mmol) in THF (2 mL) was added K ₂ C0 ₃ (93 μί, 0.19 mmol, 2.0 M in H ₂ 0). The mixture was heated at 45 °C for 15 hrs, then concentrated and the residue chromatographed over silica gel with EtOAc in hexanes (0-15%) to give the intermediate benzyl 5-amino-2,4- bis(benzyloxy)-6-(l-methyl-lH-indol-6-yl)nicotinate (160 mg, 60%) as a yellow foam. LC-MS 570.2 [M+H] ⁺ , RT 1.65 min.

Step G: To a solution of the intermediate (30 mg, 0.053 mmol) in CH ₂ CI ₂ (1 mL) and MeOH (1 mL) was added 10% Pd/C (20 mg). The mixture was stirred under a balloon of H ₂ for 1.3 hrs, then filtered, concentrated and the residue chromato graphed over silica gel with MeOH in CH ₂ C1 ₂ (0-15%) to give the title compound (11 mg, 69%) as an off-white solid. LC-MS 300.2 [M+H] ⁺ , RT 0.98 min. 1H NMR (500 MHz, DMSO- ₆ ) δ ppm 3.86 (s, 3H), 6.56 (dd, J=3.2, 0.9 Hz, 1H), 7.37 (dd, J=8.5, 1.6 Hz, 1H), 7.48 (d, J=3.2 Hz, 1H), 7.63 (d, J=8.5 Hz, 1H), 7.83 (d, J=0.9 Hz, 1H).

Biological Examples

The following in vitro biological examples demonstrate the usefulness of the compounds of the present description for treating Neisseria gonorrhoeae.

The antibacterial activity from a microbroth dilution method in either or both Fastidious Broth (FB) and FB containing 40 mg/mL Human Serum Albumin (HSA), as indicated, may be represented by the minimum inhibitory concentration (MIC in μg/mL). The MIC value is the lowest concentration of drug which prevents macroscopically visible growth under test conditions.

In the following tables, a MIC value between > 12.5 μg/mL and < 150 μg/mL is indicated by a single star (*), a MIC value between > 3.5 μg/mL and < 12.5 μg/mL is indicated by two stars (**), a MIC value between > 1.0 μg/mL and < 3.5 μg/mL is indicated by three stars (***) and a MIC value of < 1.0 μg/mL is indicated by four stars (****).

Example 1

Antibacterial activity of test compounds against N. gonorrhoeae WHO isolate F (13477) was compared in FB (Table 1) and FB containing 40 mg/mL HSA.

Table 1

Cpd 13477 Cpd 13477 Cpd 13477

1 ** **** 34 ***

2 **** **** 35 ***

3 **** J9 **** ****

4 **** 20 **** 37 **** Cpd 13477 Cpd 13477 Cpd 13477

5 *** 21 ** 38 ***

6 ** 22 **** 39 **

7 * 23 **** 40 **

8 * 24 *** 41 ****

9 *** 25 **** 42 ****

10 **** 26 ** 43 ****

11 ** 28 **** 44 *

12 **** 29 **** 49 *

13 *** 30 **** 50 *

14 **** 31 **** 51 **

15 **** 32 *** 52 **

16 *** 33 **** 53 ***

The antibacterial activity of Compound 53 against N. gonorrhoeae WHO isolate F (13477) in FB containing 40 mg/mL HSA is ** (two stars).

Example 2

Antibacterial activity of test compounds against N. gonorrhoeae WHO isolates G, K, L and M (13478, 13479, 13480 and 13481, respectively) is shown in Table 2.

Table 2

Cpd 13478 13479 13480 13481 Cpd 13478 13479 13480 13481

1 * * * * 28 ** * ** **

2 ** *** *** *** 29 **** * * **

3 * * * * 30 *** ** *** ***

4 ** * * ** 31 *** ** *** ***

5 ** * * * 32 * * * *

6 * * * * 33 **** *** **** ***

7 * * * * 34 ** * * *

8 * * * * 35 ** * * *

9 *** *** *** *** 36 * * * *

10 * * * * 37 *** * * **

11 * * * * 38 ** * * * Cpd 13478 13479 13480 13481 Cpd 13478 13479 13480 13481

12 **** ** ** ** 39 * * * *

13 *** ** *** *** 40 * * * *

14 **** * ** ** 41 **** **** **** ****

15 *** ** ** ** 42 ** * * *

16 * * *** *** 43 *** * * *

17 * * * * 44 * * * *

18 ** * * * 45 *** *** **** ****

19 *** ** *** *** 46 *** *** *** ***

20 * * * * 47 *** ** *** ***

21 * * * * 48 *** *** **** ***

22 ** ** ** ** 49 * * * *

23 *** ** *** *** 50 * * * *

24 ** * * * 51 ** ** ** **

25 ** * * * 52 * * * **

26 * * * * 53 ** * ** **

Example 3

Antibacterial activity of test compounds against a streptomycin-resistant

N. gonorrhoeae FA 1090 isolate was compared in FB (Table 3) and FB containing 40 mg/mL HSA.

Table 3

Cpd FA1090 Cpd FA1090 Cpd FA1090

2 **** **** 23 ****

4 **** **** 29 ****

5 *** **** 3 _Q ****

12 **** ** 2J ****

14 **** *** ****

15 ****

The antibacterial activity of Compound 41 against the streptomycin-resistant

N. gonorrhoeae FA 1090 isolate in FB containing 40 mg/mL HSA is * (one star). Example 4

Antibacterial activity of test compounds against ciprofloxacin-resistant AKl and AK2 isolates, penicillin-sensitive wild-type N. gonorrhoeae FA19 and the LG24 clinical isolate is shown in Table 4.

Table 4

Cpd AKl AK2 FA19 LG24 Cpd AKl AK2 FA19 LG24

2 **** **** **** **** 23 **** **** **** ****

4 **** **** **** **** 24 **** *** *** ****

5 *** *** **** **** 27 *** *** **** ****

12 *** *** **** **** 28 *** *** *** ***

14 **** **** **** **** 29 **** **** **** ****

15 **** **** **** **** 30 **** **** **** ****

19 **** **** **** **** 31 **** **** **** ****

22 **** **** **** ****

Example 5

Antibacterial activity of test compounds against N. gonorrhoeae tetracycline-resistant LGB24, penicillin-resistant LGB3 and ampicillin-resistant LGB50 isolates and an MS 11 isolate is shown in Table 5.

Table 5

Cpd LGB24 LGB3 LGB50 MS11 Cpd LGB24 LGB3 LGB50 MS11

2 **** **** **** *** 23 **** **** **** ****

4 **** **** **** *** 24 ** ** ** *

5 *** *** *** *** 27 *** *** *** ***

12 **** **** **** **** 28 *** *** *** ***

14 **** **** **** **** 29 **** **** **** ****

15 **** **** **** **** 30 **** **** **** ***

19 **** **** **** **** 31 **** **** *** ***

22 **** **** **** *** Example 6

Antibacterial activity of test compounds against the wild-type N. gonorrhoeae isolate 49226 is shown in Table 6.

Table 6

Cpd 49226 Cpd 49226 Cpd 49226

4 **** j4 **** ****

Example 7

In Vivo Mouse Model Background

The usefulness of the compounds of the present description for treating Neisseria gonorrhoeae may be demonstrated in an in vivo mouse model developed by the adaptation of several published protocols (see, Jerse, A.E., Experimental Gonococcal Genital Tract Infection and Opacity Protein Expression in estradiol-treated mice. Infection and Immunity, 1999, 67(l l):5699-5708; and, Cole, J.E. et al., Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor Under Ovarian Control. Infection and Immunity, 2010, 78(4): 1629- 1641).

Compound efficacy is demonstrated when all mice in a treatment group are completely clear of N. gonorrhoeae after 5 full days post-treatment (100% clearance).

Bacterial clearance is defined as the number of mice in the treatment group free of

N. gonorrhoeae expressed as a percentage of the total. Complete bacterial clearance (100% clearance) for the treatment group equates to an approximate log 4 reduction in bacterial count for the group. Compounds that achieve less than 100% clearance for the treatment group have an average maximal log drop value calculated by the following equation:

Maximal Log Drop = log(average Day 2 bacterial count for all mice) - log(average lowest bacterial count post dose for all mice)

Study Conduct

On Day -2 of the study, ovariectomized Balb/c female mice (5 weeks old - Charles River Laboratory) are implanted with a single 17 -estradiol pellet (0.5 mg, 21 day release) subcutaneously and begin treatment with a combination of vancomycin HC1, streptomycin sulfate (0.6 mg and 0.3 mg, respectively, IP, BID) and trimethoprim sulfate (0.8 mg, PO, BID). The antibiotic combination is administered to control commensal flora induced by the high level of ΐνβ-estradiol resulting from the implanted pellet. Combined antibiotic treatment continues from Day -2 to Day 1 of the study. After Day 1, mice are dosed with streptomycin only (0.6 mg, IP, QD).

On Day 0 of the study, mice are inoculated with a form of N. gonorrhoeae (target 1 x 10 CFU) suspended in saline. Following inoculation, and for the 7 days of the study, the bacterial count is determined by daily vaginal swabbing using sterile swabs.

On Day 1 of the study, mice are randomized into treatment groups according to bacterial count. The treatment groups (n=10) included a vehicle control, a positive control (such as ciprofloxacin, 30 mg/kg) and test compound group. The treatment groups are dosed with a single dose (mg/kg) either orally or IP. The vehicle control, positive control and test compound oral dose is administered in a mixture of HPMC (0.5%) and Tween 80 (0.1%) and the IP dose is administered in a mixture of DMSO (3%) in saline.

Example 8

Combinations with Antibacterial Agents The in vitro effects of compounds described herein in combination with a known antibacterial or antibiotic agent may be investigated in various organisms using the microdilution checkerboard method for the measurement of additive or synergistic effect. Assays can be performed in a 96- well checkerboard titration format, with serial dilutions of each compound to identify the lowest MIC value ^g/mL) at which the combination completely inhibits colony formation. The ability of a combination of one or more compounds described herein with known agents to either act synergistically, additively, indifferently or antagonistically can be determined. A synergistic effect is demonstrated when the activity of the separate agents are combined and the result is greater than the expected arithmetic sum of each agents activity alone. The fractional inhibitory

concentration (FIC) is a quantitative measure of such drug interactions, where the fractional inhibition indices are calculated using the checkerboard method in a 96-well microtiter plate. Combined activity is synergistic when the FIC value is < 0.5; combined activity is additive when the FIC value is > 0.5 and < 2; combined activity that is not different from the agents alone when the FIC value is > 2 and < 4; and, combined activity is antagonistic when the FIC value is > 4.

Without regard to whether a document cited in the present application was specifically and individually indicated as being incorporated by reference, all documents referred to herein are incorporated by reference for any and all purposes to the same extent as if each individual reference was fully set forth herein.

Having now fully described the subject matter of the claims, it will be understood by those having ordinary skill in the art that the same can be performed within a wide range of equivalents without affecting the scope of the subject matter or embodiments described herein. It is intended that the appended claims be interpreted to include all such equivalents.