MORGAN BRADLEY P (US)
COLLIBEE SCOTT (US)
MAKINO TAKUYA (JP)
KUROSAKI TOSHIO (JP)
HONJO ERIKO (JP)
KOIZUMI YUKA (JP)
WO2014040077A1 | 2014-03-13 | |||
WO2004054584A1 | 2004-07-01 |
US5846514A | 1998-12-08 | |||
US6334997B1 | 2002-01-01 | |||
US6410254B1 | 2002-06-25 | |||
US6743599B1 | 2004-06-01 | |||
US7202051B1 | 2007-04-10 | |||
US7378254B2 | 2008-05-27 |
T.H. GREENEG. M. WUTS: "Protective Groups in Organic Synthesis", 1999, JOHN WILEY & SONS
BERGE ET AL.: "Pharmaceutical Salts", J. PHARMACEUTICAL SCIENCES, vol. 66, no. 1, January 1977 (1977-01-01), pages 1 - 19, XP002675560, DOI: 10.1002/jps.2600660104
DEAN, D.: "Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development", CURR. PHARM. DES., vol. 6, no. 10, 2000
KABALKA, G. ET AL.: "The Synthesis of Radiolabeled Compounds via Organometallic Intermediates", TETRAHEDRON, vol. 45, no. 21, 1989, pages 6601 - 21
EVANS, E.: "Synthesis of radiolabeled compounds", J. RADIOANAL. CHEM., vol. 64, no. 1-2, 1981, pages 9 - 32
HERRMANN ET AL., BIOCHEM., vol. 32, no. 28, 1993, pages 7255 - 7263
CLAIMS WHAT IS CLAIMED IS: 1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: Z1, Z2, and Z3 are, independently of each other, CH, CR3, or N, provided that at least one of Z1, Z2, and Z3 is CH or CR3; R1 is unsubstituted C3-C4 alkyl; each R3 is independently halogen, C1-C6-alkyl, C1-C6-haloakyl, C1-C6-alkoxy, C1-C6-haloakoxy, C3-C12-cycloalkyl, or 3-12 membered heterocycloalkyl; R4 is C6-C12-aryl optionally substituted with one to five R4A, 5-12 membered heteroaryl optionally substituted with one to five R4B, C3-C12 cycloalkyl optionally substituted with one to five R4C, 4-12 membered heterocycloalkyl optionally substituted with one to five R4D, or 4-12 membered heterocycloalkenyl optionally substituted with one to five R4E; each R4A is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, NH(C1-C6-haloalkyl), N(C1-C6-alkyl)(C1-C6-haloalkyl), N(C1-C6-haloalkyl)2, NH(C1-C6- alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkylene-(C6- C12-aryl))2, NH(C3-C12 cycloalkyl), N(C1-C6-alkyl)(C3-C12 cycloalkyl), N(C3-C12 cycloalkyl)2, NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl optionally substituted with one to five R4B1, 4-12 membered heterocycloalkyl optionally substituted with one to five R4B1, C1-C6-alkylene-OH, C1- C6-alkylene-CONH2, C1-C6-alkylene-(C3-C12 cycloalkyl), C1-C6-alkylene-(4-12 membered heterocycloalkyl), C6-C12-aryl, and 5-12 membered heteroaryl; each R4B is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, NH(C1-C6-haloalkyl), N(C1-C6-alkyl)(C1-C6-haloalkyl), N(C1-C6-haloalkyl)2, NH(C1-C6- alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkylene-(C6- C12-aryl))2, NH(C3-C12 cycloalkyl), N(C1-C6-alkyl)(C3-C12 cycloalkyl), N(C3-C12 cycloalkyl)2, NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl optionally substituted with one to five R4B1, 4-12 membered heterocycloalkyl optionally substituted with one to five R4B1, C1-C6-alkylene-OH, C1- C6-alkylene-CONH2, C1-C6-alkylene-(C3-C12 cycloalkyl), C1-C6-alkylene-(4-12 membered heterocycloalkyl), and 5-12 membered heteroaryl; each R4B1 is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, and C1-C6-alkylene-OH; each R4C is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NHC(O)-C1-C6-alkyl, and C1-C6-alkylene-OH; each R4D is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NHC(O)-C1-C6-alkyl, and C1-C6-alkylene-OH; each R4E is independently selected from the group consisting of oxo, halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NHC(O)-C1-C6-alkyl, and C1-C6-alkylene-OH; R5 is OH, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C12 cycloalkyl, 3-12 membered heterocycloalkyl, or C6-C12-aryl; R6 and R7, independently of each other, are selected from the group consisting of H, C1-C6-alkyl, C1-C6-haloalkyl, C3-C12 cycloalkyl optionally substituted with one to five R8, 4-12 membered heterocycloalkyl optionally substituted with one to five R8, C6-C12-aryl optionally substituted with one to five R8, 5-12 membered heteroaryl optionally substituted with one to five R8, C1-C6- alkylene-OH, C1-C6-alkylene-(C3-C12 cycloalkyl), C1-C6-alkylene-(4-12 membered heterocycloalkyl), C1-C6-alkylene-(C6-C12-aryl), and C1-C6-alkylene-(5-12 membered heteroaryl); each R8 is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6- haloalkyl, OH, C1-C6-alkoxy, C1-C6-alkylene-OH, and C1-C6-haloalkoxy; n is 0, 1, 2, 3, or 4; p is 1, 2, or 3; and provided that the compound of Formula (I) is not a compound selected from the group consisting of: 4-(3-methylbenzoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-one, 4-(2-chlorobenzoyl)-3-isobutyl-3,4-dihydroquinoxalin-2(1H)-one, and 4-(4-(tert-butyl)benzoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-one. 2. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (I-a), (I-b), (I-c), (I-d), or (I-e): or a pharmaceutically acceptable salt thereof. 3. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (II): or a pharmaceutically acceptable salt thereof. 4. The compound of claim 3, wherein the compound of formula (II) is a compound of formula (II-a), (II-b), (II-c), (II-d), or (II-e): or a pharmaceutically acceptable salt thereof. 5. The compound of claim 3 or 4, wherein the compound of formula (II) is a compound of formula (II-a): or a pharmaceutically acceptable salt thereof. 6. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from the group consisting of prop-1-yl, prop-2-yl, but-2-yl, and 2- methylprop-1-yl. 7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, wherein R3 is halogen or C3-C12-cycloalkyl. 8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt thereof, wherein R3 is halogen. 9. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt thereof, wherein R3 is C3-C6-cycloalkyl. 10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt thereof, wherein n is 0 or 1. 11. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein R2 is -C(=O)R4. 12. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R4 is C6-C12-aryl optionally substituted with one to five R4A, 5-12 membered heteroaryl optionally substituted with one to five R4B, C3-C12 cycloalkyl, 4-12 membered heterocycloalkyl optionally substituted with one to five R4D, or 4-12 membered heterocycloalkenyl optionally substituted with one to five R4E. 13. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R4 is C6-C12-aryl substituted with one to five R4A and R4A is halo or C1-C6-alkyl. 14. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R4 is 5-12 membered heteroaryl substituted with one to five R4B and R4B is selected from the group consisting of halo, C1-C6-alkyl, C1-C6-haloalkoxy, NH2, N(C1-C6-alkyl)2, NH(C1-C6-haloalkyl), N(C1-C6-alkyl)(C1-C6-haloalkyl), NH(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C3-C12 cycloalkyl), NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl, 4-12 membered heterocycloalkyl optionally substituted with one to five R4B1, C1-C6-alkylene-OH, C1-C6-alkylene-CONH2, C1-C6-alkylene- (C3-C12 cycloalkyl), and 5-12 membered heteroaryl. 15. The compound of claim 14, or a pharmaceutically acceptable salt thereof, wherein R4B is 4-12 membered heterocycloalkyl substituted with one to five R4B1 and R4B1 is halo or C1-C6- alkoxy. 16. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R4 is 4-12 membered heterocycloalkyl substituted with one to five R4D and R4D is selected from the group consisting of halo, C1-C6-alkyl, OH, NHC(O)-C1-C6-alkyl, and C1-C6-alkylene-OH. 17. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R4 is 4-12 membered heterocycloalkenyl substituted with one to five R4E and R4E is oxo or C1-C6- alkyl. 18. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein 19. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R5 is OH or C6-C12-aryl. 20. The compound of claim 18 or 19, or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2. 21. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein R2 is -C(=O)NR6R7. 22. The compound of claim 21, or a pharmaceutically acceptable salt thereof, wherein R6 and R7, independently of each other, are selected from the group consisting of H, C1-C6-alkyl, C1-C6- haloalkyl, C3-C12 cycloalkyl, C6-C12-aryl optionally substituted with one to five R8, 5-12 membered heteroaryl optionally substituted with one to five R8, C1-C6-alkylene-OH, C1-C6- alkylene-(C3-C12 cycloalkyl), C1-C6-alkylene-(C6-C12-aryl), and C1-C6-alkylene-(5-12 membered heteroaryl). 23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein each R8 is independently selected from the group consisting of halo, C1-C6-alkyl, C1-C6-alkylene-OH, and C1-C6-alkoxy. 24. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt thereof, wherein R2 is -C(=O)OCH3; 25. A compound selected from the compounds of Table 2, or a pharmaceutically acceptable salt thereof. 26. A compound selected from the group consisting of compounds 1-133, or a pharmaceutically acceptable salt thereof. 27. A compound of the formula: , or a pharmaceutically acceptable salt thereof. 28. A compound of the formula: , or a pharmaceutically acceptable salt thereof. 29. A compound of the formula: , or a pharmaceutically acceptable salt thereof. 30. A pharmaceutical composition comprising a compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier. 31. The pharmaceutical composition of claim 30, wherein the pharmaceutical composition is formulated for oral, sublingual, subcutaneous, parenteral, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration. 32. A method for treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty, in a subject, comprising administering to the subject an effective amount of the compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31. 33. A method for treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies, in a subject, comprising administering to the subject an effective amount of the compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31. 34. A method for treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction, in a subject, comprising administering to the subject an effective amount of the compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31. 35. Use of a compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for the manufacture of a medicament for treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. 36. Use of a compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for the manufacture of a medicament for treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. 37. Use of a compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for the manufacture of a medicament for treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. 38. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for use in treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. 39. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for use in treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. 40. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 30 or 31, for use in treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. |
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0069] In some embodiments, provided herein is a compound of formula (I-a): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0070] In some embodiments, provided herein is a compound of formula (I-b): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0071] In some embodiments, provided herein is a compound of formula (I-c): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0072] In some embodiments, provided herein is a compound of formula (I-d): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0073] In some embodiments, provided herein is a compound of formula (I-e): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0074] In some embodiments, provided herein is a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (II-a), (II-b), (II-c), (II-d), or (II-e):
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0075] In some embodiments, provided herein is a compound of formula (II-a): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0076] In some embodiments, provided herein is a compound of formula (II-b): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0077] In some embodiments, provided herein is a compound of formula (II-c): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0078] In some embodiments, provided herein is a compound of formula (II-d): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0079] In some embodiments, provided herein is a compound of formula (II-e): or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0080] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 1 is propyl or butyl. In some embodiments, R 1 is prop-1-yl, prop-2-yl, but-1-yl, but-2-yl, or 2- methylprop-1-yl. In some embodiments, R 1 is prop-1-yl, prop-2-yl, but-2-yl, or 2-methylprop-1- yl. In some embodiments, . In some embodiments, R 1 is propyl. In some embodiments, R 1 is prop-1-yl or prop-2- yl. In some embodiments, R 1 is . In some embodiments, R 1 is butyl. In some embodiments, R 1 is but-1-yl, but-2-yl, or 2-methylprop-1-yl. . In some embodiments, R 1 is In some embodiments, R 1 is prop-2-yl. In some embodiments, R 1 is but-1-yl. In some embodiments, R 1 is but-2-yl. In some embodiments, R 1 is 2-methylprop-1-yl. In some embodiments, R 1 is . In some embodiments, R 1 is . In some embodiments, R 1 is some embodiments, R 1 is . In some embodiments, R 1 is . [0081] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, n is 0, 1, 2, 3, or 4. In some embodiments, n is 0 or 1. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. [0082] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, each R 3 is independently halogen, C1-C6-alkyl, C1-C6-haloakyl, C1-C6-alkoxy, C1-C6-haloakoxy, C3-C12- cycloalkyl, or 3-12 membered heterocycloalkyl. In other embodiments, each R 3 is independently halogen or C 3 -C 12 -cycloalkyl. In other embodiments, each R 3 is independently halogen or C 3 -C 6 - cycloalkyl. In some embodiments, each R 3 is independently halogen. In some embodiments, each R 3 is independently fluoro, chloro, or bromo. In certain embodiments, each R 3 is fluoro. In other embodiments, each R 3 is chloro. In another embodiment, each R 3 is bromo. In some embodiments, each R 3 is independently C 3 -C 12 -cycloalkyl. In some embodiments, each R 3 is independently C3-C6-cycloalkyl. In one embodiment, each R 3 is cyclopropyl. In another embodiment, each R 3 is cyclobutyl. In one embodiment, each R 3 is cyclopentyl. In one embodiment, each R 3 is cyclohexyl. [0083] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, n is 1 and R 3 is halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloakyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloakoxy, C 3 -C 12 -cycloalkyl, or 3-12 membered heterocycloalkyl. In other embodiments, n is 1 and R 3 is halogen or C3-C12- cycloalkyl. In other embodiments, n is 1 and R 3 is halogen or C3-C6-cycloalkyl. In some embodiments, n is 1 and R 3 is halogen. In some embodiments, n is 1 and R 3 is fluoro, chloro, or bromo. In certain embodiments, n is 1 and R 3 is fluoro. In other embodiments, n is 1 and R 3 is chloro. In another embodiment, n is 1 and R 3 is bromo. In some embodiments, n is 1 and R 3 is C3-C12-cycloalkyl. In some embodiments, n is 1 and R 3 is C3-C6-cycloalkyl. In one embodiment, n is 1 and R 3 is cyclopropyl. In another embodiment, n is 1 and R 3 is cyclobutyl. In one embodiment, n is 1 and R 3 is cyclopentyl. In one embodiment, n is 1 and R 3 is cyclohexyl. [0084] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 2 is - -C(=O)OCH3. In some embodiments, R 2 is -C(=O)R 4 . In some embodiments, R 2 is -C(=O)-(CH 2 ) p -R 5 . In some embodiments, R 2 is -C(=O)NR 6 R 7 . In some embodiments, R 2 is -C(=O)OCH 3 . [0085] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 2 is - C(=O)R 4 and R 4 is C 6 -C 12 -aryl optionally substituted with one to five R 4A , 5-12 membered heteroaryl optionally substituted with one to five R 4B , C3-C12 cycloalkyl optionally substituted with one to five R 4C , 4-12 membered heterocycloalkyl optionally substituted with one to five R 4D , or 4-12 membered heterocycloalkenyl optionally substituted with one to five R 4E . In some embodiments, R 2 is -C(=O)R 4 and R 4 is C6-C12-aryl optionally substituted with one to five R 4A , 5-12 membered heteroaryl optionally substituted with one to five R 4B , 4-12 membered heterocycloalkyl optionally substituted with one to five R 4D , or 4-12 membered heterocycloalkenyl optionally substituted with one to five R 4E . [0086] In some embodiments, R 2 is -C(=O)R 4 and R 4 is unsubstituted C6-C12-aryl. In some embodiments, R 4 is C6-C12-aryl substituted with one to five R 4A . In some embodiments, R 4 is unsubstituted phenyl. In some embodiments, R 4 is phenyl substituted with one to five R 4A . In C 6 -alkyl, C 1 -C 6 -haloalkyl, OH, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, NH 2 , NH(C 1 -C 6 -alkyl), N(C 1 - C6-alkyl)2, NH(C1-C6-haloalkyl), N(C1-C6-alkyl)(C1-C6-haloalkyl), N(C1-C6-haloalkyl)2, NH(C1- C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkylene-(C6- C 12 -aryl)) 2 , NH(C 3 -C 12 cycloalkyl), N(C 1 -C 6 -alkyl)(C 3 -C 12 cycloalkyl), N(C 3 -C 12 cycloalkyl) 2 , NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl optionally substituted with one to five R 4B1 , 4-12 membered heterocycloalkyl optionally substituted with one to five R 4B1 , C1-C6-alkylene-OH, C1- C 6 -alkylene-CONH 2 , C 1 -C 6 -alkylene-(C 3 -C 12 cycloalkyl), C 1 -C 6 -alkylene-(4-12 membered heterocycloalkyl), C6-C12-aryl, or 5-12 membered heteroaryl. In some embodiments, each R 4A is independently is halo or C1-C6-alkyl. In some embodiments, each R 4A is independently halo. In some embodiments, each R 4A is fluoro. In some embodiments, each R 4A is independently chloro. In some embodiments, each R 4A is independently bromo. In some embodiments, each R 4A is independently C1-C6-alkyl. In some embodiments, each R 4A is independently methyl. In some embodiments, each R 4A is independently ethyl. In some embodiments, each R 4A is independently propyl. In some embodiments, each R 4A is independently butyl. In some embodiments, each R 4A is independently pentyl. In some embodiments, each R 4A is independently hexyl. [0087] In some embodiments, R 2 is -C(=O)R 4 and R 4 is unsubstituted 5-12 membered heteroaryl. In some embodiments, R 4 is 5-12 membered heteroaryl substituted with one to five R 4B . In some embodiments, R 4 is pyridinyl, pyrrolyl, pyrazolyl, isoxazolyl, thiazolyl, pyrrolopyridyl, imidazopyridyl, pyrrolopyrimidyl, pyrazolopyridyl, or pyrrolidinyl, each of optionally substituted with one to five R 4B . In some embodiments, which is unsubstituted or substituted with one to four R 4B . In some embodiments, R 4 is , which is unsubstituted or substituted with one to four R 4B . In some embodiments, is , which is unsubstituted or substituted with one to four R 4B . In some embodiments, R 4 is , which is unsubstituted or substituted with one to three R 4B . In some embodiments, , which is unsubstituted or substituted with one or two In some embodiments, R 4 is , which is unsubstituted or substituted with one to three In some embodiments, , which is unsubstituted or substituted with one to five R 4B . In some embodiments, R 4 is , which is unsubstituted or substituted with one to five R 4B . In some embodiments, R 4 is ubst tu , wh unsubstituted or substituted with one to five R 4B . In some embodiments, which is unsubstituted or substituted with one to four R 4B . In some embodiments, each R 4B is independently halo, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, OH, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, NH 2 , NH(C 1 -C 6 -alkyl), N(C 1 -C 6 -alkyl) 2 , NH(C 1 -C 6 -haloalkyl), N(C 1 -C 6 -alkyl)(C 1 -C 6 -haloalkyl), N(C1-C6-haloalkyl)2, NH(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C1-C6-alkylene-(C6-C12- aryl)), N(C 1 -C 6 -alkylene-(C 6 -C 12 -aryl)) 2 , NH(C 3 -C 12 cycloalkyl), N(C 1 -C 6 -alkyl)(C 3 -C 12 cycloalkyl), N(C3-C12 cycloalkyl)2, NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl optionally substituted with one to five R 4B1 , 4-12 membered heterocycloalkyl optionally substituted with one to five R 4B1 , C 1 -C 6 -alkylene-OH, C 1 -C 6 -alkylene-CONH 2 , C 1 -C 6 -alkylene-(C 3 -C 12 cycloalkyl), C1-C6-alkylene-(4-12 membered heterocycloalkyl), or 5-12 membered heteroaryl. In some embodiments, each R 4B is independently halo, C1-C6-alkyl, C1-C6-haloalkoxy, NH2, N(C1- C 6 -alkyl) 2 , NH(C 1 -C 6 -haloalkyl), N(C 1 -C 6 -alkyl)(C 1 -C 6 -haloalkyl), NH(C 1 -C 6 -alkylene-(C 6 -C 12 - aryl)), N(C1-C6-alkyl)(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C3-C12 cycloalkyl), NHC(O)-C1-C6-alkyl, C3-C12 cycloalkyl, 4-12 membered heterocycloalkyl optionally substituted with one to five R 4B1 , C 1 -C 6 -alkylene-OH, C 1 -C 6 -alkylene-CONH 2 , C 1 -C 6 -alkylene-(C 3 -C 12 cycloalkyl), or 5-12 membered heteroaryl. In some embodiments, each R 4B is independently halo, C1-C6-alkyl, C1-C6-haloalkoxy, NH2, N(C1-C6-alkyl)2, NH(C1-C6-haloalkyl), N(C1-C6-alkyl)(C1- C6-haloalkyl), NH(C1-C6-alkylene-(C6-C12-aryl)), N(C1-C6-alkyl)(C3-C12 cycloalkyl), NHC(O)- C 1 -C 6 -alkyl, C 3 -C 12 cycloalkyl, 4-12 membered heterocycloalkyl optionally substituted with one to five R 4B1 , C1-C6-alkylene-OH, C1-C6-alkylene-CONH2, C1-C6-alkylene-(C3-C12 cycloalkyl), or 5-12 membered heteroaryl. In some embodiments, R 4B is halo. In some embodiments, R 4B is fluoro. In some embodiments, R 4B is chloro. In some embodiments, R 4B is C 1 -C 6 -alkyl. In some embodiments, R 4B is methyl. In some embodiments, R 4B is ethyl. In some embodiments, R 4B is propyl. In some embodiments, R 4B is C 1 -C 6 -haloalkoxy. In some embodiments, . In some embodiments, R 4B is . In some embodiments, R 4B is NH2. In some embodiments, R 4B is N(C 1 -C 6 -alkyl) 2 . In some embodiments, R 4B is . In some embodiments, R 4B is . In some embodiments, R 4B is NH(C 1 -C 6 -haloalkyl). In some embodiments, . some embodiments, R 4B is N(C1-C6-alkyl)(C1-C6- haloalkyl). In some embodiments, . some embodiments, R 4B is . In some embodiments, R 4B is NH(C1-C6-alkylene-(C6-C12-aryl)). In some embodiments, . some embodiments, R 4B is N(C1-C6-alkyl)(C1-C6- alkylene-(C6-C12-aryl)). In some embodiments, . some embodiments, R 4B is N(C 1 -C 6 -alkyl)(C 3 -C 12 cycloalkyl). In some embodiments, . some embodiments, R 4B is NHC(O)-C 1 -C 6 -alkyl. In some embodiments, R 4B is . In some embodiments, R 4B is C 3 -C 12 cycloalkyl. In some embodiments, R 4B is . In some embodiments, R 4B is . In some embodiments, R 4B is 4-12 membered heterocycloalkyl optionally substituted with one to five R 4B1 . In some embodiments, R 4B is , which is optionally substituted with one to five R 4B1 . In some embodiments, R 4B is , which is optionally substituted with one to five R 4B1 . In some embodiments, R 4B is is optionally substituted with one to five R 4B1 . In some embodiments, R 4B is , which is optionally substituted with one to five R 4B1 . In some embodiments, R 4B is C 1 -C 6 -alkylene-OH. In some embodiments, . some embodiments, R 4B is C1-C6-alkylene-CONH2. In some embodiments, . embodiments, R 4B is C1-C6-alkylene-(C3-C12 cycloalkyl). In some embodiments, R 4B is . In some embodiments, R 4B is 5-12 membered heteroaryl. In some embodiments, R 4B is . In some embodiments, R 4B1 is halo, C1-C6-alkyl, C1-C6-haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, and C1-C6-alkylene- OH. In some embodiments, R 4B1 is halo or C 1 -C 6 -alkoxy. In some embodiments, R 4B1 is halo. In some embodiments, R 4B1 is fluoro. In some embodiments, R 4B1 is C1-C6-alkoxy. In some embodiments, R 4B1 is methoxy. [0088] In some embodiments, R 2 is -C(=O)R 4 and R 4 is unsubstituted 4-12 membered heterocycloalkyl. In some embodiments, R 4 is 4-12 membered heterocycloalkyl substituted with one to five R 4D . In some embodiments, R 4 is indolinyl, azetidinyl, or piperidinyl, each of which is optionally substituted with one to five R 4D . In some embodiments, R 4 is , , each of which is optionally substituted with one to five R 4D . In some embodiments, R 4 is , which is unsubstituted or substituted with one to five R 4D . In some embodiments, R 4 is , which is unsubstituted or substituted with one to five R 4D . In some embodiments, R 4 is , which is unsubstituted or substituted with one to five R 4D . In some embodiments, R 4 is , which is unsubstituted or substituted with one to five R 4D . In some embodiments, R 4D is C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, OH, C 1 -C 6 - alkoxy, C1-C6-haloalkoxy, NHC(O)-C1-C6-alkyl, or C1-C6-alkylene-OH. In some embodiments, R 4D is halo, C1-C6-alkyl, OH, NHC(O)-C1-C6-alkyl, or C1-C6-alkylene-OH. In some embodiments, R 4D is halo. In some embodiments, R 4D is fluoro. In some embodiments, R 4D is C 1 - C6-alkyl. In some embodiments, R 4D is methyl. In some embodiments, R 4D is OH. In some embodiments, R 4D is NHC(O)-C1-C6-alkyl. In some embodiments, R 4D is NHC(O)Me. In some embodiments, R 4D is C 1 -C 6 -alkylene-OH. In some embodiments, R 4D is CH 2 OH. [0089] In some embodiments, R 2 is -C(=O)R 4 and R 4 is unsubstituted 4-12 membered heterocycloalkenyl. In some embodiments, R 4 is 4-12 membered heterocycloalkenyl substituted with one to five R 4E . In some embodiments, R 4 is pyridonyl. In some embodiments, R 4 is , which is optionally substituted with one to four R 4E . In some embodiments, R 4E is oxo, halo, C1-C6-alkyl, C1-C6-haloalkyl, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, NHC(O)-C1- C6-alkyl, or C1-C6-alkylene-OH. In some embodiments, R 4E is oxo or C1-C6-alkyl. In some embodiments, R 4E is oxo. In some embodiments, R 4E is C 1 -C 6 -alkyl. In some embodiments, R 4E is methyl. [0090] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 2 is - C(=O)-(CH2)p-R 5 and R 5 is OH, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C12 cycloalkyl, 3-12 membered heterocycloalkyl, or C6-C12-aryl. In some embodiments, R 5 is OH or C6-C12-aryl. In some embodiments, R 5 is OH. In some embodiments, R 5 is C 6 -C 12 -aryl. In some embodiments, R 5 is phenyl. In some embodiments, p is 1, 2, or 3. In some embodiments, p is 1 or 2. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. [0091] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 2 is - C(=O)NR 6 R 7 , and R 6 and R 7 , independently of each other, are H, C1-C6-alkyl, C1-C6-haloalkyl, C 3 -C 12 cycloalkyl optionally substituted with one to five R 8 , 4-12 membered heterocycloalkyl optionally substituted with one to five R 8 , C6-C12-aryl optionally substituted with one to five R 8 , 5-12 membered heteroaryl optionally substituted with one to five R 8 , C1-C6-alkylene-OH, C1-C6- alkylene-(C 3 -C 12 cycloalkyl), C 1 -C 6 -alkylene-(4-12 membered heterocycloalkyl), C 1 -C 6 - alkylene-(C6-C12-aryl), or C1-C6-alkylene-(5-12 membered heteroaryl). In some embodiments, R 6 and R 7 , independently of each other, are H, C1-C6-alkyl, C1-C6-haloalkyl, C3-C12 cycloalkyl, C6- C 12 -aryl optionally substituted with one to five R 8 , 5-12 membered heteroaryl optionally substituted with one to five R 8 , C 1 -C 6 -alkylene-OH, C 1 -C 6 -alkylene-(C 3 -C 12 cycloalkyl), C 1 -C 6 - alkylene-(C6-C12-aryl), and C1-C6-alkylene-(5-12 membered heteroaryl). In some embodiments, R 6 is H and R 7 is H. In some embodiments, R 6 is H and R 7 is C1-C6-alkyl. In some embodiments, R 6 is H and R 7 is methyl. In some embodiments, R 6 is H and R 7 is ethyl. In some embodiments, R 6 is H and R 7 is C 1 -C 6 -haloalkyl. In some embodiments, . In some embodiments, R 6 is C 1 -C 6 -alkyl and R 7 is C 1 -C 6 -haloalkyl. In some embodiments, R 6 is methyl . [0092] In some embodiments, R 6 is H and R 7 is C3-C12 cycloalkyl optionally substituted with one to five R 8 . In some embodiments, R 6 is H and R 7 is unsubstituted cyclohexyl. In some embodiments, R 6 is H and R 7 is cyclobutyl substituted with one R 8 . In some embodiments, R 6 is some embodiments, . some embodiments, R 6 is . some embodiments, . some embodiments, R 6 is H and R 7 is C 6 -C 12 -aryl optionally substituted with one to five R 8 . In some embodiments, R 6 is H and R 7 is phenyl substituted with one R 8 . In some embodiments, . some embodiments, . some embodiments, R 6 is H and R 7 is . , . some embodiments, R 6 is embodiments, R 6 is H and R 7 is 5-12 membered heteroaryl optionally substituted with one to five R 8 . In some embodiments, R 6 is H and R 7 is unsubstituted pyridin-3-yl. In some embodiments, R 6 is H and R 7 is unsubstituted pyridin-4-yl. In some embodiments, R 6 is H and R 7 is . , . some embodiments, R 6 is H and R 7 is . In some embodiments, R 6 is H and R 7 is . In some embodiments, R 6 is H and R 7 is C1-C6-alkylene-OH. In some embodiments, R 6 is H and R 7 . , . some embodiments, R 6 is C 1 - C 6 -alkyl and R 7 is C 1 -C 6 -alkylene-OH. In some embodiments, R 6 is methyl . some embodiments, R 6 is methyl . some embodiments, R 6 is H and R 7 is 4-12 membered heterocycloalkyl optionally substituted with one to five R 8 . In some embodiments, . some embodiments, . some embodiments, . some embodiments, R 6 is H and R 7 is . , . some embodiments, R 6 is H . , . some embodiments, R 6 is . some embodiments, R 6 is H and R 7 is C1-C6-alkylene-(C3-C12 cycloalkyl). In some embodiments, R 6 is H and R 7 is . In some embodiments, R 6 is H and R 7 is C 1 -C 6 -alkylene-(C 6 -C 12 -aryl). In some embodiments, R 6 is H and R 7 is . In some embodiments, . some embodiments, R 8 is halo, C 1 -C 6 -alkyl, C1-C6-haloalkyl, OH, C1-C6-alkoxy, C1-C6-alkylene-OH, or C1-C6-haloalkoxy. In some embodiments, R 8 is halo, C 1 -C 6 -alkyl, C 1 -C 6 -alkylene-OH, or C 1 -C 6 -alkoxy. In some embodiments, R 8 is halo. In some embodiments, R 8 is fluoro. In some embodiments, R 8 is C 1 -C 6 - alkyl. In some embodiments, R 8 is methyl. In some embodiments, R 8 is C1-C6-alkylene-OH. In some embodiments, . some embodiments, R 8 is C 1 -C 6 -alkoxy. In some embodiments, R 8 is methoxy. [0093] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, R 2 is , , , , , , ,
ome embodiments, R some embodiments, R
embodiments, In some embodiments, . some embodiments, R 2 is
embodiments, . some embodiments, R 2 is . , . embodiments, . some embodiments, embodiments, R 2 is . , . embodiments, , embodiments, , some embodiments, some embodiments, . some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, some embodiments, In some embodiments, some embodiments, some some embodiments, R 2 is . In some embodiments, R 2 is . In some embodiments, . some embodiments, . some embodiments, . some embodiments, . , . some embodiments, . some embodiments, . some embodiments, . some embodiments, . some embodiments, . some embodiments, . some embodiments, . , . In some embodiments, . some embodiments, . In some embodiments, . some embodiments, . In some embodiments, . some embodiments, . embodiments, . some embodiments, . . , . ,
. In some embodiments, . some embodiments, . [0094] In one aspect, provided herein is a compound of the formula: , or a pharmaceutically acceptable salt thereof. [0095] In another aspect, provided herein is a compound of the formula: or a pharmaceutically acceptable salt thereof. [0096] In another aspect, provided herein is a compound of the formula: or a pharmaceutically acceptable salt thereof. [0097] In some embodiments of the compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof, the compounds are not 4-(3-methylbenzoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-one , 4-(2- chlorobenzoyl)-3-isobutyl-3,4-dihydroquinoxalin-2(1H)-one, or 4-(4-(tert-butyl)benzoyl)-3- propyl-3,4-dihydroquinoxalin-2(1H)-one. [0098] In some embodiments, provided herein is a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from Table 2. Table 2
[0099] In some variations, any of the compounds described herein, such as a compound of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e) or any variation thereof, or a compound of Table 2, may be deuterated (e.g., a hydrogen atom is replaced by a deuterium atom). In some of these variations, the compound is deuterated at a single site. In other variations, the compound is deuterated at multiple sites. Deuterated compounds can be prepared from deuterated starting materials in a manner similar to the preparation of the corresponding non-deuterated compounds. Hydrogen atoms may also be replaced with deuterium atoms using other method known in the art. [0100] In one aspect, provided herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is a compound selected from the compounds of Table 2, or a pharmaceutically acceptable salt thereof. [0101] In one aspect, provided herein is a compound selected from the compounds of Table 2, or a pharmaceutically acceptable salt thereof. [0102] In one aspect, provided herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is selected from the group consisting of compounds 1-133, or a pharmaceutically acceptable salt thereof. [0103] In one aspect, provided herein is a compound selected from the group consisting of compounds 1-133, or a pharmaceutically acceptable salt thereof. [0104] In one aspect, provided herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is selected from the group consisting of: 4-(6-chloronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 6-chloro-4-(6-chloronicotinoyl)-3-propyl-3,4-dihydroquinoxal in-2(1H)-one; 4-(6-methylnicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 5-bromo-4-(6-chloronicotinoyl)-3-propyl-3,4-dihydroquinoxali n-2(1H)-one; 4-(6-chloronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 4-(6-fluoronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 5-cyclopropyl-4-(6-methylnicotinoyl)-3-propyl-3,4-dihydroqui noxalin-2(1H)-one; N-(6-methylpyridin-3-yl)-3-oxo-2-propyl-3,4-dihydroquinoxali ne-1(2H)-carboxamide; 3-propyl-4-(1H-pyrrole-2-carbonyl)-3,4-dihydroquinoxalin-2(1 H)-one; 4-benzoyl-3-propyl-3,4-dihydroquinoxalin-2(1H)-one; 4-isonicotinoyl-3-propyl-3,4-dihydroquinoxalin-2(1H)-one; 4-nicotinoyl-3-propyl-3,4-dihydroquinoxalin-2(1H)-one; 4-(1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydroquin oxalin-2(1H)-one; 4-(3-methylisoxazole-4-carbonyl)-3-propyl-3,4-dihydroquinoxa lin-2(1H)-one; 3-propyl-4-(thiophene-2-carbonyl)-3,4-dihydroquinoxalin-2(1H )-one; 4-(5-methylnicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 4-(3-fluorobenzoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-one ; 4-(5-fluoronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 4-(3-phenylpropanoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-o ne; 4-(5-chloronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)- one; 4-(3,4-difluorobenzoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H) -one; N-(5-(3-oxo-2-propyl-1,2,3,4-tetrahydroquinoxaline-1-carbony l)pyridin-2-yl)acetamide; 4-(6-(1H-pyrrol-1-yl)nicotinoyl)-3-propyl-3,4-dihydroquinoxa lin-2(1H)-one; 4-(6-(difluoromethoxy)nicotinoyl)-3-propyl-3,4-dihydroquinox alin-2(1H)-one; 3-propyl-4-(6-(trifluoromethoxy)nicotinoyl)-3,4-dihydroquino xalin-2(1H)-one; 3-propyl-4-(1H-pyrrolo[2,3-b]pyridine-5-carbonyl)-3,4-dihydr oquinoxalin-2(1H)-one; 4-(6-aminonicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-o ne; 4-(6-(dimethylamino)nicotinoyl)-3-propyl-3,4-dihydroquinoxal in-2(1H)-one; 4-(6-(piperidin-1-yl)nicotinoyl)-3-propyl-3,4-dihydroquinoxa lin-2(1H)-one; 4-(1-ethyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydroquino xalin-2(1H)-one; 4-(1-(cyclopropylmethyl)-1H-pyrazole-4-carbonyl)-3-propyl-3, 4-dihydroquinoxalin-2(1H)-one; 4-(1-cyclobutyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydro quinoxalin-2(1H)-one; 4-(6-(ethyl(methyl)amino)nicotinoyl)-3-propyl-3,4-dihydroqui noxalin-2(1H)-one; 3-propyl-4-(6-((2,2,2-trifluoroethyl)amino)nicotinoyl)-3,4-d ihydroquinoxalin-2(1H)-one; 4-(6-(azepan-1-yl)nicotinoyl)-3-propyl-3,4-dihydroquinoxalin -2(1H)-one; 4-(6-(benzylamino)nicotinoyl)-3-propyl-3,4-dihydroquinoxalin -2(1H)-one; 4-(6-(cyclopropyl(methyl)amino)nicotinoyl)-3-propyl-3,4-dihy droquinoxalin-2(1H)-one; 4-(6-(3-fluoroazetidin-1-yl)nicotinoyl)-3-propyl-3,4-dihydro quinoxalin-2(1H)-one; 4-(6-(benzyl(methyl)amino)nicotinoyl)-3-propyl-3,4-dihydroqu inoxalin-2(1H)-one; 4-(6-(3-methoxyazetidin-1-yl)nicotinoyl)-3-propyl-3,4-dihydr oquinoxalin-2(1H)-one; 4-(6-(3-fluoropyrrolidin-1-yl)nicotinoyl)-3-propyl-3,4-dihyd roquinoxalin-2(1H)-one; 4-(6-(3,3-difluoroazetidin-1-yl)nicotinoyl)-3-propyl-3,4-dih ydroquinoxalin-2(1H)-one; 4-(6-(3,3-difluoropyrrolidin-1-yl)nicotinoyl)-3-propyl-3,4-d ihydroquinoxalin-2(1H)-one; 4-(6-(methyl(3,3,3-trifluoropropyl)amino)nicotinoyl)-3-propy l-3,4-dihydroquinoxalin-2(1H)- one; 4-(1,3-dimethyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydro quinoxalin-2(1H)-one; N-cyclohexyl-3-oxo-2-propyl-3,4-dihydroquinoxaline-1(2H)-car boxamide; 3-oxo-2-propyl-N-(pyridin-3-yl)-3,4-dihydroquinoxaline-1(2H) -carboxamide; 3-oxo-2-propyl-N-(pyridin-4-yl)-3,4-dihydroquinoxaline-1(2H) -carboxamide; N-benzyl-3-oxo-2-propyl-3,4-dihydroquinoxaline-1(2H)-carboxa mide; 3-oxo-N-(1-phenylethyl)-2-propyl-3,4-dihydroquinoxaline-1(2H )-carboxamide; N-(cyclohexylmethyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1 (2H)-carboxamide; 4-(indoline-1-carbonyl)-3-propyl-3,4-dihydroquinoxalin-2(1H) -one; N-(2-methoxyphenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1( 2H)-carboxamide; N-(3-methoxyphenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1( 2H)-carboxamide; N-(4-methoxyphenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1( 2H)-carboxamide; N-(2-fluorophenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1(2 H)-carboxamide; N-(3-fluorophenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1(2 H)-carboxamide; N-(4-fluorophenyl)-3-oxo-2-propyl-3,4-dihydroquinoxaline-1(2 H)-carboxamide; N-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2-propyl-3,4-dihydroquino xaline-1(2H)-carboxamide; 3-oxo-2-propyl-N-(o-tolyl)-3,4-dihydroquinoxaline-1(2H)-carb oxamide; 3-oxo-2-propyl-N-(m-tolyl)-3,4-dihydroquinoxaline-1(2H)-carb oxamide; 3-oxo-2-propyl-N-(p-tolyl)-3,4-dihydroquinoxaline-1(2H)-carb oxamide; 3-(sec-butyl)-4-(1-methyl-1H-pyrazole-4-carbonyl)-3,4-dihydr oquinoxalin-2(1H)-one; 6-chloro-4-(1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-di hydroquinoxalin-2(1H)-one; 4-(imidazo[1,5-a]pyridine-6-carbonyl)-3-propyl-3,4-dihydroqu inoxalin-2(1H)-one; 4-(imidazo[1,5-a]pyridine-7-carbonyl)-3-propyl-3,4-dihydroqu inoxalin-2(1H)-one; 4-(1-(2-hydroxyethyl)-1H-pyrazole-4-carbonyl)-3-propyl-3,4-d ihydroquinoxalin-2(1H)-one; 3-isobutyl-4-(1-methyl-1H-pyrazole-4-carbonyl)-3,4-dihydroqu inoxalin-2(1H)-one; 5-bromo-4-(1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dih ydroquinoxalin-2(1H)-one; 3-propyl-4-(pyrrolo[1,2-c]pyrimidine-3-carbonyl)-3,4-dihydro quinoxalin-2(1H)-one; 3-propyl-4-(1H-pyrazole-4-carbonyl)-3,4-dihydroquinoxalin-2( 1H)-one; 3-(sec-butyl)-4-(1H-pyrazole-4-carbonyl)-3,4-dihydroquinoxal in-2(1H)-one; 3-propyl-4-(1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3,4-dihyd roquinoxalin-2(1H)-one; 4-(6-aminonicotinoyl)-3-(sec-butyl)-3,4-dihydroquinoxalin-2( 1H)-one; 3-(sec-butyl)-4-(6-oxo-1,6-dihydropyridine-3-carbonyl)-3,4-d ihydroquinoxalin-2(1H)-one; 4-(1-cyclopropyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydr oquinoxalin-2(1H)-one; 3-isopropyl-4-(1-methyl-1H-pyrazole-4-carbonyl)-3,4-dihydroq uinoxalin-2(1H)-one; 3-(sec-butyl)-4-(1-(2-hydroxyethyl)-1H-pyrazole-4-carbonyl)- 3,4-dihydroquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(1H-pyrazole-3-carbonyl)-3,4-dihydroquinoxal in-2(1H)-one; 2-(4-(2-(sec-butyl)-3-oxo-1,2,3,4-tetrahydroquinoxaline-1-ca rbonyl)-1H-pyrazol-1-yl)acetamide; 3-isopropyl-4-(1-methyl-6-oxo-1,6-dihydropyridine-3-carbonyl )-3,4-dihydroquinoxalin-2(1H)- one; 4-(6-aminonicotinoyl)-3-isopropyl-3,4-dihydroquinoxalin-2(1H )-one; 3-isopropyl-4-(1H-pyrazolo[3,4-b]pyridine-5-carbonyl)-3,4-di hydroquinoxalin-2(1H)-one; 4-(1-cyclopropyl-1H-pyrazole-4-carbonyl)-3-isopropyl-3,4-dih ydroquinoxalin-2(1H)-one; 3-isopropyl-4-(6-oxo-1,6-dihydropyridine-3-carbonyl)-3,4-dih ydroquinoxalin-2(1H)-one; 3-isopropyl-4-(1H-pyrazole-4-carbonyl)-3,4-dihydroquinoxalin -2(1H)-one; 3-isopropyl-4-(1-methyl-6-oxo-1,6-dihydropyridine-3-carbonyl )-3,4-dihydropyrido[2,3- b]pyrazin-2(1H)-one; 2-isopropyl-1-(1-methyl-1H-pyrazole-4-carbonyl)-1,4-dihydrop yrido[3,4-b]pyrazin-3(2H)-one; 2-(sec-butyl)-1-(1-methyl-1H-pyrazole-4-carbonyl)-1,4-dihydr opyrido[3,4-b]pyrazin-3(2H)-one; 2-(sec-butyl)-1-(6-oxo-1,6-dihydropyridine-3-carbonyl)-1,4-d ihydropyrido[3,4-b]pyrazin-3(2H)- one; 2-(sec-butyl)-1-(1-methyl-6-oxo-1,6-dihydropyridine-3-carbon yl)-1,4-dihydropyrido[3,4- b]pyrazin-3(2H)-one; 3-(sec-butyl)-4-(1-methyl-6-oxo-1,6-dihydropyridine-3-carbon yl)-3,4-dihydropyrido[2,3- b]pyrazin-2(1H)-one; 3-(sec-butyl)-4-(1-methyl-1H-pyrazole-4-carbonyl)-3,4-dihydr opyrido[2,3-b]pyrazin-2(1H)-one; 7-(sec-butyl)-8-(1-methyl-1H-pyrazole-4-carbonyl)-7,8-dihydr opteridin-6(5H)-one; 2-(sec-butyl)-1-(1-methyl-1H-pyrazole-4-carbonyl)-1,4-dihydr opyrido[2,3-b]pyrazin-3(2H)-one; 2-isobutyl-1-(1-methyl-1H-pyrazole-4-carbonyl)-1,4-dihydropy rido[3,4-b]pyrazin-3(2H)-one; 1-benzoyl-2-(sec-butyl)-1,4-dihydropyrido[3,4-b]pyrazin-3(2H )-one; 2-(sec-butyl)-1-(3-methylbenzoyl)-1,4-dihydropyrido[3,4-b]py razin-3(2H)-one; 2-(sec-butyl)-3-oxo-3,4-dihydroquinoxaline-1(2H)-carboxamide ; 2-(sec-butyl)-5-fluoro-3-oxo-3,4-dihydroquinoxaline-1(2H)-ca rboxamide; 3-(sec-butyl)-4-(3-hydroxyazetidine-1-carbonyl)-3,4-dihydroq uinoxalin-2(1H)-one; 2-(sec-butyl)-N-methyl-3-oxo-3,4-dihydroquinoxaline-1(2H)-ca rboxamide; 2-(sec-butyl)-N-ethyl-3-oxo-3,4-dihydroquinoxaline-1(2H)-car boxamide; 3-(sec-butyl)-4-(pyrrolidine-1-carbonyl)-3,4-dihydroquinoxal in-2(1H)-one; 2-(sec-butyl)-N-(2-hydroxyethyl)-3-oxo-3,4-dihydroquinoxalin e-1(2H)-carboxamide; 3-(sec-butyl)-4-(3-hydroxypyrrolidine-1-carbonyl)-3,4-dihydr oquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(3-(hydroxymethyl)pyrrolidine-1-carbonyl)-3, 4-dihydroquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(3-(hydroxymethyl)pyrrolidine-1-carbonyl)-3, 4-dihydroquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(2-hydroxyacetyl)-3,4-dihydroquinoxalin-2(1H )-one; 3-(sec-butyl)-4-(3-hydroxypropanoyl)-3,4-dihydroquinoxalin-2 (1H)-one; 3-(sec-butyl)-4-(3-(hydroxymethyl)azetidine-1-carbonyl)-3,4- dihydroquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(3-fluoroazetidine-1-carbonyl)-3,4-dihydroqu inoxalin-2(1H)-one; 2-(sec-butyl)-7-fluoro-3-oxo-3,4-dihydroquinoxaline-1(2H)-ca rboxamide; 3-(sec-butyl)-4-(3-hydroxypiperidine-1-carbonyl)-3,4-dihydro quinoxalin-2(1H)-one; 2-(sec-butyl)-N-(3-hydroxypropyl)-N-methyl-3-oxo-3,4-dihydro quinoxaline-1(2H)-carboxamide; 3-(sec-butyl)-4-(3-(hydroxymethyl)piperidine-1-carbonyl)-3,4 -dihydroquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(3,3-difluoroazetidine-1-carbonyl)-3,4-dihyd roquinoxalin-2(1H)-one; 3-(sec-butyl)-4-(4-hydroxypiperidine-1-carbonyl)-3,4-dihydro quinoxalin-2(1H)-one; N-(1-(2-(sec-butyl)-3-oxo-1,2,3,4-tetrahydroquinoxaline-1-ca rbonyl)azetidin-3-yl)acetamide; 3-(sec-butyl)-4-(3-fluoropyrrolidine-1-carbonyl)-3,4-dihydro quinoxalin-2(1H)-one; 3-(sec-butyl)-4-(3-hydroxy-3-methylazetidine-1-carbonyl)-3,4 -dihydroquinoxalin-2(1H)-one; 2-(sec-butyl)-N-(oxetan-3-yl)-3-oxo-3,4-dihydroquinoxaline-1 (2H)-carboxamide; 2-(sec-butyl)-N-(2,2-difluoroethyl)-3-oxo-3,4-dihydroquinoxa line-1(2H)-carboxamide; 2-(sec-butyl)-N-(2,2-difluoroethyl)-N-methyl-3-oxo-3,4-dihyd roquinoxaline-1(2H)-carboxamide; methyl 2-(sec-butyl)-3-oxo-3,4-dihydroquinoxaline-1(2H)-carboxylate ; 2-(sec-butyl)-3-oxo-N-(pyrrolidin-3-yl)-3,4-dihydroquinoxali ne-1(2H)-carboxamide; 2-(sec-butyl)-N-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-oxo-3, 4-dihydroquinoxaline-1(2H)- carboxamide; 2-(sec-butyl)-3-oxo-N-(2-oxaspiro[3.3]heptan-6-yl)-3,4-dihyd roquinoxaline-1(2H)-carboxamide; 2-(sec-butyl)-N-(1-methylpyrrolidin-3-yl)-3-oxo-3,4-dihydroq uinoxaline-1(2H)-carboxamide; 2-(sec-butyl)-N-(1-(2-hydroxyethyl)piperidin-4-yl)-3-oxo-3,4 -dihydroquinoxaline-1(2H)- carboxamide; 2-(sec-butyl)-N-(2-hydroxyethyl)-N-methyl-3-oxo-3,4-dihydroq uinoxaline-1(2H)-carboxamide; 2-(sec-butyl)-N-(3-hydroxycyclobutyl)-3-oxo-3,4-dihydroquino xaline-1(2H)-carboxamide; and 2-(sec-butyl)-N-(3-hydroxycyclobutyl)-3-oxo-3,4-dihydroquino xaline-1(2H)-carboxamide; or a pharmaceutically acceptable salt thereof. Also provided herein are, where applicable, any and all stereoisomers of the compounds depicted herein, including geometric isomers (e.g., cis/trans isomers or E/Z isomers), enantiomers, diastereomers, or mixtures thereof in any ratio, including racemic mixtures. [0105] Any formula given herein, such as formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II- a), (II-b), (II-c), (II-d), or (II-e), is intended to represent compounds having structures depicted by the structural formula as well as certain variations or forms. In particular, compounds of any formula given herein may have asymmetric centers and therefore exist in different enantiomeric or diastereomeric forms. All optical isomers and stereoisomers of the compounds of the general formula, and mixtures thereof in any ratio, are considered within the scope of the formula. Thus, any formula given herein is intended to represent a racemate, one or more enantiomeric forms, one or more diastereomeric forms, one or more atropisomeric forms, and mixtures thereof in any ratio. Where a compound of Table 2 is depicted with a particular stereochemical configuration, also provided herein is any alternative stereochemical configuration of the compound, as well as a mixture of stereoisomers of the compound in any ratio. For example, where a compound of Table 2 has a stereocenter that is in an “S” stereochemical configuration, also provided herein is enantiomer of the compound wherein that stereocenter is in an “R” stereochemical configuration. Likewise, when a compound of Table 2 has a stereocenter that is in an “R” configuration, also provided herein is enantiomer of the compound in an “S” stereochemical configuration. Also provided are mixtures of the compound with both the “S” and the “R” stereochemical configuration. Additionally, if a compound of Table 2 has two or more stereocenters, also provided are any enantiomer or diastereomer of the compound. For example, if a compound of Table 2 contains a first stereocenter and a second stereocenter with “R” and “R” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “S” and “S” stereochemical configurations, respectively, “S” and “R” stereochemical configurations, respectively, and “R” and “S” stereochemical configurations, respectively. If a compound of Table 2 contains a first stereocenter and a second stereocenter with “S” and “S” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “R” and “R” stereochemical configurations, respectively, “S” and “R” stereochemical configurations, respectively, and “R” and “S” stereochemical configurations, respectively. If a compound of Table 2 contains a first stereocenter and a second stereocenter with “S” and “R” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “R” and “S” stereochemical configurations, respectively, “R” and “R” stereochemical configurations, respectively, and “S” and “S” stereochemical configurations, respectively. Similarly, if a compound of Table 2 contains a first stereocenter and a second stereocenter with “R” and “S” stereochemical configurations, respectively, also provided are stereoisomers of the compound having first and second stereocenters with “S” and “R” stereochemical configurations, respectively, “R” and “R” stereochemical configurations, respectively, and “S” and “S” stereochemical configurations, respectively. Furthermore, certain structures may exist as geometric isomers (i.e., cis and trans isomers), as tautomers, or as atropisomers. Additionally, any formula given herein is intended to refer also to any one of hydrates, solvates, and amorphous and crystalline forms of such compounds, and mixtures thereof, even if such forms are not listed explicitly. In some embodiments, the solvent is water and the solvates are hydrates. [0106] Representative examples of compounds detailed herein, including intermediates and final compounds, are depicted in the tables and elsewhere herein. It is understood that in one aspect, any of the compounds may be used in the methods detailed herein, including, where applicable, intermediate compounds that may be isolated and administered to an individual or subject. [0107] The compounds depicted herein may be present as salts even if salts are not depicted, and it is understood that the compositions and methods provided herein embrace all salts and solvates of the compounds depicted here, as well as the non-salt and non-solvate form of the compound, as is well understood by the skilled artisan. In some embodiments, the salts of the compounds provided herein are pharmaceutically acceptable salts. [0108] In one variation, the compounds herein are synthetic compounds prepared for administration to an individual or subject. In another variation, compositions are provided containing a compound in substantially pure form. In another variation, provided are pharmaceutical compositions comprising a compound detailed herein and a pharmaceutically acceptable carrier. In another variation, methods of administering a compound are provided. The purified forms, pharmaceutical compositions and methods of administering the compounds are suitable for any compound or form thereof detailed herein. [0109] Any variation or embodiment of Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 4A , R 4B , R 4C , R 4D , R 4E , R 4B1 , n and p provided herein can be combined with every other variation or embodiment of Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 4A , R 4B , R 4C , R 4D , R 4E , R 4B1 , n and p, the same as if each and every combination had been individually and specifically described. [0110] Other embodiments will be apparent to those skilled in the art from the following detailed description. [0111] As used herein, when any variable occurs more than one time in a chemical formula, its definition on each occurrence is independent of its definition at every other occurrence. [0112] Formula (I) includes all subformulas thereof. For example, formula (I) includes compounds of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a pharmaceutically acceptable salt thereof. [0113] The names for compounds 1-133 provided herein, as shown in Table 2 and Examples 1-12, are provided by ChemDraw Professional 18.2.0.48. . One of skilled in the art would understand that the compounds may be named or identified using various commonly recognized nomenclature systems and symbols. By way of example, the compounds may be named or identified with common names, systematic or non-systematic names. The nomenclature systems and symbols that are commonly recognized in the art of chemistry include, for example, Chemical Abstract Service (CAS), ChemBioDraw Ultra, and International Union of Pure and Applied Chemistry (IUPAC). Compositions [0114] Also provided are compositions, such as pharmaceutical compositions, that include a compound disclosed and/or described herein and one or more additional medicinal agents, pharmaceutical agents, adjuvants, carriers, excipients, and the like. Suitable medicinal and pharmaceutical agents include those described herein. In some embodiments, the pharmaceutical composition includes a pharmaceutically acceptable excipient or adjuvant and at least one chemical entity as described herein. Examples of pharmaceutically acceptable excipients include, but are not limited to, mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, and magnesium carbonate. In some embodiments, provided are compositions, such as pharmaceutical compositions that contain one or more compounds described herein, or a pharmaceutically acceptable salt thereof. [0115] In some embodiments, provided is a pharmaceutically acceptable composition comprising a compound of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II- d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. In some aspects, a composition may contain a synthetic intermediate that may be used in the preparation of a compound described herein. The compositions described herein may contain any other suitable active or inactive agents. [0116] Any of the compositions described herein may be sterile or contain components that are sterile. Sterilization can be achieved by methods known in the art. Any of the compositions described herein may contain one or more compounds or conjugates that are substantially pure. [0117] Also provided are packaged pharmaceutical compositions, comprising a pharmaceutical composition as described herein and instructions for using the composition to treat a patient suffering from a disease or condition described herein. Methods of Use [0118] The compounds and compositions detailed herein, such as a pharmaceutical composition comprising a compound of any formula provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient, may be used in methods of administration and treatment as provided herein. [0119] Further, the invention relates to a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Furthermore, the invention relates to a pharmaceutical composition for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, in a subject, comprising a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. Furthermore, the invention relates to an agent for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, comprising a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0120] Furthermore, the invention relates to a pharmaceutical composition for treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, in a subject, comprising a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. Furthermore, the invention relates to an agent for treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, comprising a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0121] Moreover, the invention relates to use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof in a subject. [0122] Moreover, the invention relates to use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0123] In one aspect, provided herein is the use of the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0124] In one aspect, provided herein is the use of the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0125] In one aspect, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0126] In one aspect, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0127] In one aspect, provided herein is a method for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, comprising administering to the subject an effective amount of the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. Further, the “subject” is a human or a non-human animal in need of the prevention or treatment, and in one embodiment, a human in need of the prevention or treatment. [0128] In one aspect, provided herein is a method for treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere in a subject, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof, comprising administering to the subject an effective amount of the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. Further, the “subject” is a human or a non-human animal in need of the prevention or treatment, and in one embodiment, a human in need of the prevention or treatment. [0129] In one aspect, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in medical therapy. Such medical therapy may be relating to a disease or condition responsive to modulation of the contractility of the skeletal sarcomere, for example, modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0130] In one aspect, a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, modulates the contractility of the skeletal sarcomere. Specifically, the compounds modulate the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. As used in this context, “modulate” means either increasing or decreasing activity. In some instances, a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, potentiates (i.e., increases activity) of one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. [0131] In another aspect, provided herein is a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, inhibits (i.e., decreases activity) of one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. As used in this context, “activation of the fast skeletal muscle fiber such as myofibril” means to amplify the response of fast skeletal muscle fiber (such as myofibril) to stimulation/Ca 2+ . [0132] In some aspects, provided herein is a method of preventing or treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post-surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or an effective amount of a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0133] In some aspects, provided herein is a method of treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post-surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I- e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or an effective amount of a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0134] In some aspects, provided herein is a method for preventing or treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0135] In some aspects, provided herein is a method for treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I- a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0136] In some aspects, provided herein is a method for preventing or treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0137] In some aspects, provided herein is a method for treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0138] In some aspects, provided herein is a method for preventing or treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0139] In some aspects, provided herein is a method for treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction, in a subject, comprising administering to the subject an effective amount of a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof. [0140] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for preventing or treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post- surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject. [0141] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post- surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject. [0142] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for preventing or treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. [0143] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. [0144] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for preventing or treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. [0145] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. [0146] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for preventing or treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. [0147] In some aspects, provided herein is the use of a compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. [0148] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in preventing or treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post- surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject. [0149] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating: frailty associated with old age (termed sarcopenia); cachexia syndromes associated with diseases such as cancer, heart failure, chronic obstructive pulmonary disease (COPD), renal disease, and chronic kidney disease/dialysis; diseases and disorders of the central nervous system (CNS); neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and myasthenia gravis, peripheral neuropathies, Charcot-Marie-Tooth disease, Parkinson’s disease, stroke, spinal cord injury, and motor units disorders; muscular myopathies, including body myositis myopathy, muscular dystrophies (limb girdle, facioscapulohumeral, oculopharyngeal), steroid myopathy, and mitochondrial myopathies; rehabilitation-related deficits: recovery from surgery (e.g., post- surgical muscle weakness), prolonged bed rest, immobilization/disuse atrophy, post-hip fracture recovery, ICU neuromyopathy, post trauma, stroke rehabilitation; Peripheral Vascular Disease (PVD) or Peripheral Arterial Disease (PAD) (e.g., claudication), metabolic syndrome, chronic fatigue syndrome, obesity, and frailty due to aging; post-anesthesia recovery or reversal of neuromuscular blockade; obstructive sleep apnea; chronic fatigue syndrome; metabolic syndrome, metabolic/ischemic disorders, or claudication; obesity; dysfunctions of pelvic floor and urethral/anal sphincter muscles (e.g., urinary incontinence such as stress urinary incontinence (SUI) and mixed urinary incontinence (MUI), and fecal incontinence); post-spinal cord injury (SCI) muscle dysfunction; ventilator-induced muscle weakness; or spinocerebral ataxias or demyelinating diseases, including multiple sclerosis, post-polio syndrome, or any combination of the foregoing, in a subject. [0150] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in preventing or treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. [0151] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating a disease or condition selected from the group consisting of peripheral vascular disease, peripheral arterial disease, rehabilitation-related deficits, metabolic syndrome, obesity, ventilator-induced muscle weakness, chronic fatigue syndrome, neuromuscular disorders, conditions of muscle wasting, muscular myopathies, muscle atrophy, muscle fatigue, and frailty in a subject. [0152] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in preventing or treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. [0153] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating a disease or condition selected from the group consisting of amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), myasthenia gravis, and muscular myopathies in a subject. [0154] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in preventing or treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. [0155] In some aspects, provided herein is the compound of the formula (I), such as a compound of formula (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or a compound of Table 2, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating a disease or condition selected from the group consisting of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), fecal incontinence, frailty, sarcopenia, chronic obstructive pulmonary disease (COPD), cachexia syndrome, muscle wasting caused by heart failure, cancer, or chronic kidney disease/dialysis, post-spinal cord injury (SCI) muscle dysfunction, and post-stroke muscle dysfunction in a subject. Dosages [0156] The compounds and compositions disclosed and/or described herein are administered at a therapeutically effective dosage, e.g., a dosage sufficient to provide treatment for the disease state. While human dosage levels have yet to be optimized for the chemical entities described herein, generally, a daily dose ranges from about 0.01 to 100 mg/kg of body weight; in some embodiments, from about 0.05 to 10.0 mg/kg of body weight, and in some embodiments, from about 0.10 to 1.4 mg/kg of body weight. Thus, for administration to a 70 kg person, in some embodiments, the dosage range would be about from 0.7 to 7000 mg per day; in some embodiments, about from 3.5 to 700.0 mg per day, and in some embodiments, about from 7 to 100.0 mg per day. The amount of the chemical entity administered will be dependent, for example, on the subject and disease state being treated, the severity of the affliction, the manner and schedule of administration and the judgment of the prescribing physician. For example, an exemplary dosage range for oral administration is from about 5 mg to about 500 mg per day, and an exemplary intravenous administration dosage is from about 5 mg to about 500 mg per day, each depending upon the compound pharmacokinetics. [0157] A daily dose is the total amount administered in a day. A daily dose may be, but is not limited to be, administered each day, every other day, each week, every 2 weeks, every month, or at a varied interval. In some embodiments, the daily dose is administered for a period ranging from a single day to the life of the subject. In some embodiments, the daily dose is administered once a day. In some embodiments, the daily dose is administered in multiple divided doses, such as in 2, 3, or 4 divided doses. In some embodiments, the daily dose is administered in 2 divided doses. [0158] Administration of the compounds and compositions disclosed and/or described herein can be via any accepted mode of administration for therapeutic agents including, but not limited to, oral, sublingual, subcutaneous, parenteral, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration. In some embodiments, the compound or composition is administered orally or intravenously. In some embodiments, the compound or composition disclosed and/or described herein is administered orally. [0159] Pharmaceutically acceptable compositions include solid, semi-solid, liquid and aerosol dosage forms, such as tablet, capsule, powder, liquid, suspension, suppository, and aerosol forms. The compounds disclosed and/or described herein can also be administered in sustained or controlled release dosage forms (e.g., controlled/sustained release pill, depot injection, osmotic pump, or transdermal (including electrotransport) patch forms) for prolonged timed, and/or pulsed administration at a predetermined rate. In some embodiments, the compositions are provided in unit dosage forms suitable for single administration of a precise dose. [0160] The compounds disclosed and/or described herein can be administered either alone or in combination with one or more conventional pharmaceutical carriers or excipients (e.g., mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, sodium crosscarmellose, glucose, gelatin, sucrose, magnesium carbonate). If desired, the pharmaceutical composition can also contain minor amounts of nontoxic auxiliary substances such as wetting agents, emulsifying agents, solubilizing agents, pH buffering agents and the like (e.g., sodium acetate, sodium citrate, cyclodextrine derivatives, sorbitan monolaurate, triethanolamine acetate, triethanolamine oleate). Generally, depending on the intended mode of administration, the pharmaceutical composition will contain about 0.005% to 95%, or about 0.5% to 50%, by weight of a compound disclosed and/or described herein. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington’s Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania. [0161] In some embodiments, the compositions will take the form of a pill or tablet and thus the composition may contain, along with a compounds disclosed and/or described herein, one or more of a diluent (e.g., lactose, sucrose, dicalcium phosphate), a lubricant (e.g., magnesium stearate), and/or a binder (e.g., starch, gum acacia, polyvinylpyrrolidine, gelatin, cellulose, cellulose derivatives). Other solid dosage forms include a powder, marume, solution or suspension (e.g., in propylene carbonate, vegetable oils or triglycerides) encapsulated in a gelatin capsule. [0162] Liquid pharmaceutically administrable compositions can, for example, be prepared by dissolving, dispersing or suspending etc. a compound disclosed and/or described herein and optional pharmaceutical additives in a carrier (e.g., water, saline, aqueous dextrose, glycerol, glycols, ethanol or the like) to form a solution or suspension. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, as emulsions, or in solid forms suitable for dissolution or suspension in liquid prior to injection. The percentage of the compound contained in such parenteral compositions depends, for example, on the physical nature of the compound, the activity of the compound and the needs of the subject. However, percentages of active ingredient of 0.01% to 10% in solution are employable, and may be higher if the composition is a solid which will be subsequently diluted to another concentration. In some embodiments, the composition will comprise from about 0.2 to 2% of a compound disclosed and/or described herein in solution. [0163] Pharmaceutical compositions of the compounds disclosed and/or described herein may also be administered to the respiratory tract as an aerosol or solution for a nebulizer, or as a microfine powder for insufflation, alone or in combination with an inert carrier such as lactose. In such a case, the particles of the pharmaceutical composition may have diameters of less than 50 microns, or in some embodiments, less than 10 microns. [0164] In addition, pharmaceutical compositions can include a compound disclosed and/or described herein and one or more additional medicinal agents, pharmaceutical agents, adjuvants, and the like. Suitable medicinal and pharmaceutical agents include those described herein. Kits [0165] Also provided are articles of manufacture and kits containing any of the compounds or pharmaceutical compositions provided herein. The article of manufacture may comprise a container with a label. Suitable containers include, for example, bottles, vials, and test tubes. The containers may be formed from a variety of materials such as glass or plastic. The container may hold a pharmaceutical composition provided herein. The label on the container may indicate that the pharmaceutical composition is used for preventing, treating or suppressing a condition described herein, and may also indicate directions for either in vivo or in vitro use. [0166] In one aspect, provided herein are kits containing a compound or composition described herein and instructions for use. The kits may contain instructions for use in the treatment of a heart disease in an individual or subject in need thereof. A kit may additionally contain any materials or equipment that may be used in the administration of the compound or composition, such as vials, syringes, or IV bags. A kit may also contain sterile packaging. Combinations [0167] The compounds and compositions described and/or disclosed herein may be administered alone or in combination with other therapies and/or therapeutic agents useful in the treatment of the aforementioned disorders, diseases, or conditions. General Synthetic Methods [0168] Compounds of formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II- d), or (II-e) will now be described by reference to illustrative synthetic schemes for their general preparation below and the specific examples that follow. Artisans will recognize that, to obtain the various compounds herein, starting materials may be suitably selected so that the ultimately desired substituents will be carried through the reaction scheme, with or without protection, as appropriate, to yield the desired product. Alternatively, it may be necessary or desirable to employ, in the place of the ultimately desired substituent, a suitable group that may be carried through the reaction scheme and replaced as appropriate with the desired substituent. In addition, one of skill in the art will recognize that protecting groups may be used to protect certain functional groups (for example: amino, carboxy, or side chain groups) from reaction conditions, and that such groups are removed under standard conditions when appropriate. It is also to be understood that any of the steps shown in any of the following general schemes may be used in any combination and in any order that is chemically feasible to achieve a desired intermediate or disclosed compound. Unless otherwise specified, the variables are as defined above in reference to formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e). [0169] Where it is desired to obtain a particular enantiomer of a compound, this may be accomplished from a corresponding mixture of enantiomers using any suitable conventional procedure for separating or resolving enantiomers. Thus, for example, diastereomeric derivatives may be produced by reaction of a mixture of enantiomers, e.g. a racemate, and an appropriate chiral compound. The diastereomers may then be separated by any convenient means, for example by crystallization and the desired enantiomer recovered. In another resolution process, a racemate may be separated using chiral High Performance Liquid Chromatography. Alternatively, if desired a particular enantiomer may be obtained by using an appropriate chiral intermediate in one of the processes described. [0170] Chromatography, recrystallization, and other conventional separation procedures may also be used with intermediates or final products where it is desired to obtain a particular isomer of a compound or to otherwise purify a product of a reaction. [0171] General methods of preparing compounds described herein are depicted in exemplified methods below. Variable groups in the schemes provided herein are defined as for formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (II), (II-a), (II-b), (II-c), (II-d), or (II-e), or any variation thereof. Other compounds described herein may be prepared by similar methods. [0172] In some embodiments, compounds provided herein may be synthesized according to Scheme I-A: Scheme I-A wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0173] In such embodiments, provided is a method of preparing a compound of formula (I), or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (A-4), or a salt thereof, with a compound of formula (A-5), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I), and wherein X is OH or halogen. In some embodiments, X is OH and the step of reacting the compound of formula (A-4), or a salt thereof, with the compound of formula (A-5), or a salt thereof, is performed in the presence of a coupling agent. In some embodiments, the coupling agent is 1-chloro-N,N,2-trimethylprop-1-en- 1-amine. In some embodiments, X is halogen. In some embodiments, X is chloro. In some embodiments, reaction between (A-4) and (A-5) is conducted in the presence of a base. In some embodiments, the base is DIPEA. [0174] In some embodiments, the method further comprises preparing the compound of formula (A-5), or a salt thereof, wherein X is chloro, by reacting a compound of formula R 2 -OH with a chlorinating agent. In some embodiments, the chlorinating agent is 1-chloro-N,N,2- trimethylprop-1-en-1-amine. In some embodiments, the chlorinating agent is thionyl chloride. [0175] In some embodiments, the method further comprises preparing the compound of formula (A-4), or a salt thereof, by converting a compound of formula (A-3), or a salt thereof, wherein R is C1-C6-alkyl, into the compound of formula (A-4), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I). In some embodiments, the step of converting a compound of formula (A-3), or a salt thereof, into the compound of formula (A-4), or a salt thereof, is performed in the presence of iron and an acid. In some embodiments, the acid is ammonium chloride or acetic acid. In some embodiments, the acid is ammonium chloride. In some embodiments, the acid is acetic acid. In some embodiments, the step of converting a compound of formula (A-3), or a salt thereof, into the compound of formula (A-4), or a salt thereof, is performed in the presence of a palladium catalyst. In some embodiments, the palladium catalyst is palladium on carbon or palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (A-3), or a salt thereof, into the compound of formula (A-4), or a salt thereof, is performed in the presence of H2. In some embodiments, the palladium catalyst is palladium on carbon and the step of converting a compound of formula (A-3), or a salt thereof, into the compound of formula (A-4), or a salt thereof, is performed in the presence of H2. In some embodiments, the palladium catalyst is palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (A-3), or a salt thereof, into the compound of formula (A-4), or a salt thereof, is performed in the presence of H2. In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0176] In some embodiments, the method further comprises preparing the compound of formula (A-3), or a salt thereof, wherein R is C1-C6-alkyl, by reacting a compound of formula (A-1) with a compound of formula (A-2), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I). In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0177] In some embodiments, the method further comprises preparing the compound of formula (A-3), or a salt thereof, by reacting a compound of formula (A-1) with a hydrochloride salt of a compound of formula (A-2) in the presence of a base, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (I). In some embodiments, the base is diisopropylamine or lutidine. In some embodiments, the base is diisopropylamine. In some embodiments, the base is lutidine. In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0178] In some embodiments, R 4 is -C(=O)NR 6 R 7 and the compound of formula (I), or a pharmaceutically acceptable salt thereof, is a compound of formula (A-8), or a pharmaceutically acceptable salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (I). The compound of formula (A-8), or a pharmaceutically acceptable salt thereof, can be prepared according to Scheme I-B: Scheme I-B wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0179] In such embodiments, provided is a method of preparing the compound of formula (A-8), or a pharmaceutically acceptable salt thereof, by reacting a compound of formula (A-6), or a salt thereof, with a compound of formula (A-7), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0180] In such embodiments, the method further comprises preparing the compound of formula (A-6), or a salt thereof, by reacting a compound of formula (A-4) with triphosgene and NH 3 /MeOH, wherein Z 1 , Z 2 , Z 3 , R 1 , and n are as defined for the compound of formula (I), or any variation or embodiment thereof. [0181] In some embodiments, compounds of formula (II) provided herein may be synthesized according to Scheme II-A: Scheme II-A wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II), or any variation or embodiment thereof. [0182] In such embodiments, provided is a method of preparing a compound of formula (II), or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (B-4), or a salt thereof, with a compound of formula (B-5), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II), and wherein X is OH or halogen. In some embodiments, X is OH and the step of reacting the compound of formula (B-4), or a salt thereof, with the compound of formula (B-5), or a salt thereof, is performed in the presence of a coupling agent. In some embodiments, the coupling agent is 1-chloro-N,N,2-trimethylprop-1-en- 1-amine. In some embodiments, X is halogen. In some embodiments, X is chloro. In some embodiments, reaction between (B-4) and (B-5) is conducted in the presence of a base. In some embodiments, the base is DIPEA. [0183] In some embodiments, the method further comprises preparing the compound of formula (B-5), or a salt thereof, wherein X is chloro, by reacting a compound of formula R 2 -OH with a chlorinating agent. In some embodiments, the chlorinating agent is 1-chloro-N,N,2- trimethylprop-1-en-1-amine. In some embodiments, the chlorinating agent is thionyl chloride. [0184] In some embodiments, the method further comprises preparing the compound of formula (B-4), or a salt thereof, by converting a compound of formula (B-3), or a salt thereof, wherein R is C1-C6-alkyl, into the compound of formula (B-4), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II). In some embodiments, the step of converting a compound of formula (B-3), or a salt thereof, into the compound of formula (B-4), or a salt thereof, is performed in the presence of iron and an acid. In some embodiments, the acid is ammonium chloride or acetic acid. In some embodiments, the acid is ammonium chloride. In some embodiments, the acid is acetic acid. In some embodiments, the step of converting a compound of formula (B-3), or a salt thereof, into the compound of formula (B-4), or a salt thereof, is performed in the presence of a palladium catalyst. In some embodiments, the palladium catalyst is palladium on carbon or palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (B-3), or a salt thereof, into the compound of formula (B-4), or a salt thereof, is performed in the presence of H2. In some embodiments, the palladium catalyst is palladium on carbon and the step of converting a compound of formula (B-3), or a salt thereof, into the compound of formula (B-4), or a salt thereof, is performed in the presence of H 2 . In some embodiments, the palladium catalyst is palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (B-3), or a salt thereof, into the compound of formula (B-4), or a salt thereof, is performed in the presence of H 2 . In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0185] In some embodiments, the method further comprises preparing the compound of formula (B-3), or a salt thereof, wherein R is C 1 -C 6 -alkyl, by reacting a compound of formula (B- 1) with a compound of formula (B-2), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II). In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0186] In some embodiments, the method further comprises preparing the compound of formula (B-3), or a salt thereof, by reacting a compound of formula (B-1) with a hydrochloride salt of a compound of formula (B-2) in the presence of a base, wherein Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II). In some embodiments, the base is diisopropylamine or lutidine. In some embodiments, the base is diisopropylamine. In some embodiments, the base is lutidine. In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0187] In some embodiments, R 4 is -C(=O)NR 6 R 7 and the compound of formula (II), or a pharmaceutically acceptable salt thereof, is a compound of formula (B-8), or a pharmaceutically acceptable salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II). The compound of formula (B-8), or a pharmaceutically acceptable salt thereof, can be prepared according to Scheme II-B: Scheme II-B wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II), or any variation or embodiment thereof. [0188] In such embodiments, provided is a method of preparing the compound of formula (B-8), or a pharmaceutically acceptable salt thereof, by reacting a compound of formula (B-6), or a salt thereof, with a compound of formula (B-7), or a salt thereof, wherein Z 1 , Z 2 , Z 3 , R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II), or any variation or embodiment thereof. [0189] In such embodiments, the method further comprises preparing the compound of formula (B-6), or a salt thereof, by reacting a compound of formula (B-4) with triphosgene and NH3/MeOH, wherein Z 1 , Z 2 , Z 3 , R 1 , and n are as defined for the compound of formula (II), or any variation or embodiment thereof. [0190] In some embodiments, compounds of formula (II-a) provided herein may be synthesized according to Scheme III-A: Scheme III-A wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II-a), or any variation or embodiment thereof. [0191] In such embodiments, provided is a method of preparing a compound of formula (II- a), or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (C- 4), or a salt thereof, with a compound of formula (C-5), or a salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II-a), and wherein X is OH or halogen. In some embodiments, X is OH and the step of reacting the compound of formula (C-4), or a salt thereof, with the compound of formula (C-5), or a salt thereof, is performed in the presence of a coupling agent. In some embodiments, the coupling agent is 1-chloro-N,N,2-trimethylprop-1-en-1-amine. In some embodiments, X is halogen. In some embodiments, X is chloro. In some embodiments, reaction between (C-4) and (C-5) is conducted in the presence of a base. In some embodiments, the base is DIPEA. [0192] In some embodiments, the method further comprises preparing the compound of formula (C-5), or a salt thereof, wherein X is chloro, by reacting a compound of formula R 2 -OH with a chlorinating agent. In some embodiments, the chlorinating agent is 1-chloro-N,N,2- trimethylprop-1-en-1-amine. In some embodiments, the chlorinating agent is thionyl chloride. [0193] In some embodiments, the method further comprises preparing the compound of formula (C-4), or a salt thereof, by converting a compound of formula (C-3), or a salt thereof, wherein R is C 1 -C 6 -alkyl, into the compound of formula (C-4), or a salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II-a). In some embodiments, the step of converting a compound of formula (C-3), or a salt thereof, into the compound of formula (C-4), or a salt thereof, is performed in the presence of iron and an acid. In some embodiments, the acid is ammonium chloride or acetic acid. In some embodiments, the acid is ammonium chloride. In some embodiments, the acid is acetic acid. In some embodiments, the step of converting a compound of formula (C-3), or a salt thereof, into the compound of formula (C-4), or a salt thereof, is performed in the presence of a palladium catalyst. In some embodiments, the palladium catalyst is palladium on carbon or palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (C-3), or a salt thereof, into the compound of formula (C-4), or a salt thereof, is performed in the presence of H 2 . In some embodiments, the palladium catalyst is palladium on carbon and the step of converting a compound of formula (C-3), or a salt thereof, into the compound of formula (C-4), or a salt thereof, is performed in the presence of H 2 . In some embodiments, the palladium catalyst is palladium hydroxide on carbon (Pearlman’s catalyst) and the step of converting a compound of formula (C-3), or a salt thereof, into the compound of formula (C-4), or a salt thereof, is performed in the presence of H 2 . In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0194] In some embodiments, the method further comprises preparing the compound of formula (C-3), or a salt thereof, wherein R is C 1 -C 6 -alkyl, by reacting a compound of formula (C- 1) with a compound of formula (C-2), or a salt thereof, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II-a). In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0195] In some embodiments, the method further comprises preparing the compound of formula (C-3), or a salt thereof, by reacting a compound of formula (C-1) with a hydrochloride salt of a compound of formula (C-2) in the presence of a base, wherein R 1 , R 2 , R 3 , and n are as defined for the compound of formula (II-a). In some embodiments, the base is diisopropylamine or lutidine. In some embodiments, the base is diisopropylamine. In some embodiments, the base is lutidine. In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. [0196] In some embodiments, R 4 is -C(=O)NR 6 R 7 and the compound of formula (II-a), or a pharmaceutically acceptable salt thereof, is a compound of formula (C-8), or a pharmaceutically acceptable salt thereof, wherein R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II- a). The compound of formula (C-8), or a pharmaceutically acceptable salt thereof, can be prepared according to Scheme III-B: wherein R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II-a), or any variation or embodiment thereof. [0197] In such embodiments, provided is a method of preparing the compound of formula (C-8), or a pharmaceutically acceptable salt thereof, by reacting a compound of formula (C-6), or a salt thereof, with a compound of formula (C-7), or a salt thereof, wherein R 1 , R 5 , R 6 , and n are as defined for the compound of formula (II-a), or any variation or embodiment thereof. [0198] In such embodiments, the method further comprises preparing the compound of formula (C-6), or a salt thereof, by reacting a compound of formula (C-4) with triphosgene and NH3/MeOH, wherein Z 1 , Z 2 , Z 3 , R 1 , and n are as defined for the compound of formula (II-a), or any variation or embodiment thereof. [0199] Also provided herein are intermediate compounds, or a salt thereof, to make the compounds of Formula (I) or any sub-formula thereof. In some embodiments, the intermediate compounds are the intermediate compounds shown in Generic Synthetic Schemes above. In some embodiments, the intermediate compounds are the intermediate compounds shown in the Example section below. EXAMPLES [0200] The following examples are offered to illustrate, but not to limit, the compounds, compositions, uses, and methods provided herein. In some examples, the compounds and intermediates are prepared using the general methods described above. [0201] The following abbreviations are used throughout the Examples: DIPEA (N,N- diisopropylethylamine), LRMS (low-resolution mass spectrometry), Ac (acetyl), Et (ethyl), Me (methyl), tBu (tert-butyl), APCI (atmospheric pressure chemical ionization), THF (tetrahydrofuran), DMAP (4-dimethylaminopyridine), DMF (dimethylformamide), DMSO (dimethylsulfoxide), HPLC (high-performance liquid chromatography), TEA (triethylamine), and ESI (electrospray ionization). Example 1: Synthesis of Compound 64 [0202] Step 1: Ethyl (S)-2-((5-chloro-2-nitrophenyl)amino)pentanoate. To a mixture of 4- chloro-2-fluoro-1-nitrobenzene (1.00 g, 5.7 mmol) in DMF (10 mL) was added ethyl (S)-2- aminopentanoate hydrochloride (1.14 g, 6.3 mmol) and DIPEA (2.4 mL, 14 mmol) at room temperature. The reaction mixture was heated to 70 °C and stirred overnight. The reaction mixture was then quenched with saturated ammonium chloride, extracted with 50% EtOAc/hexane, dried over MgSO4, and concentrated under reduced pressure to give ethyl (S)-2- ((5-chloro-2-nitrophenyl)amino)pentanoate (1.75 g, quantitative) as an orange oil. [0203] Step 2: (S)-6-Chloro-3-propyl-3,4-dihydroquinoxalin-2(1H)-one. To a mixture of ethyl (S)-2-((5-chloro-2-nitrophenyl)amino)pentanoate (1.74 g, 5.8 mmol) in MeOH (20 mL) and water (10 mL) was added Fe powder (2.26 g, 40.5 mmol) and NH 4 Cl (371 mg, 6.9 mmol) at room temperature. The reaction mixture was heated to 70 ℃ and stirred for 4 h, diluted with water and CHCl 3 , and filtered through a Celite pad. The filtrate was extracted with CHCl 3 , dried over MgSO 4 , concentrated, and purified using amino silica gel chromatography (0-50% EtOAc/hexane) to give (S)-6-chloro-3-propyl-3,4-dihydroquinoxalin-2(1H)-one (1.15 g, 88%) as a yellow solid. [0204] Step 3: (S)-6-Chloro-4-(1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3, 4- dihydroquinoxalin-2(1H)-one. To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (130 mg, 1.0 mmol) in CH2Cl2 (2 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (145 µL, 1.1 mmol). After stirring at room temperature for 2 h, (S)-6-chloro-3-propyl-3,4- dihydroquinoxalin-2(1H)-one (150 mg, 668 µmol) and pyridine (160 µL, 2.0 mmol) were added. The reaction mixture was stirred at room temperature overnight, then quenched with water, and then diluted with CHCl 3 . The organic layer was separated, concentrated under reduced pressure, and purified using amino silica gel chromatography (0-5% MeOH/CHCl3) to give (S)-6-chloro-4- (1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4-dihydroquinox alin-2(1H)-one (104 mg, 47%) as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 10.87 (s, 1H), 7.90 (s, 1H), 7.26 (dd, J = 2.3, 8.6 Hz, 1H), 7.19 (s, 1H), 7.15 (d, J = 2.1 Hz, 1H), 7.06 (d, J = 8.6 Hz, 1H), 4.89 (dd, J = 5.9, 8.9 Hz, 1H), 3.81 (s, 3H), 1.51 - 1.43 (m, 1H), 1.40 - 1.22 (m, 3H), 0.90-0.84 (m, 3H). LRMS (ESI) m/z 333.2 [M + H] + . Example 2: Synthesis of Compound 100 [0205] Step 1: Methyl (3-fluoro-2-nitrophenyl)-L-isoleucinate. To a mixture of 1,3- difluoro-2-nitrobenzene (1.00 g, 6.3 mmol) in DMF (5 mL) was added methyl L-isoleucinate hydrochloride (1.37 g, 7.5 mmol) and DIPEA (2.7 mL, 16.0 mmol). The reaction mixture was heated to 70 °C and stirred overnight. The reaction mixture was cooled to room temperature and water was added. The mixture was stirred for 30 min and then extracted with 20% EtOAc/hexane. The organic layer was washed with 5% NaCl, dried over MgSO4, and concentrated under reduced pressure to give methyl (3-fluoro-2-nitrophenyl)-L-isoleucinate (1.70 g, 95%) as a brown oil. [0206] Step 2: (S)-3-((S)-sec-Butyl)-8-fluoro-3,4-dihydroquinoxalin-2(1H)-o ne. To a mixture of methyl (3-fluoro-2-nitrophenyl)-L-isoleucinate (1.7 g, 5.98 mmol) in ethanol (20 mL) was added 5% Pd/C (340 mg). The reaction was stirred under a hydrogen atmosphere for 2.5 d and then filtered through a celite pad. The celite pad was washed with ethanol (10 mL), and the combined organic filtrates were heated to 80 ℃ and stirred for 1 day. A solution of ammonium chloride (384 mg, 7.18 mmol) in H 2 O (8.0 mL) was added, and the mixture was heated to 80 °C and stirred for 1 day. HCl (1 M, 7.0 mL) was added to the mixture, and the mixture was stirred at 80 °C for 2 d. The reaction mixture was then concentrated, diluted with chloroform, and neutralized with saturated sodium bicarbonate. The organic layer was separated, concentrated, and purified using silica gel chromatography (5-40% EtOAc/Hexane) followed by amino silica gel chromatography (5-50% EtOAc/hexanes) to give (S)-3-((S)-sec-butyl)-8-fluoro-3,4- dihydroquinoxalin-2(1H)-one (713 mg, 54%) as a pale yellow solid. [0207] Step 3: (S)-2-((S)-sec-Butyl)-5-fluoro-3-oxo-3,4-dihydroquinoxaline- 1(2H)- carboxamide. To an ice-cooled solution of (S)-3-((S)-sec-butyl)-8-fluoro-3,4-dihydroquinoxalin- 2(1H)-one (200 mg, 0.9 mmol) and DIPEA (462 µL, 2.7 mmol) in THF (2.0 mL) was added triphosgene (107 mg, 361 µmol). After stirring for 25 min, NH3/MeOH (7 M, 770 µL, 5.4 mmol) was added to the reaction mixture. The reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was then concentrated and diluted with CHCl 3 and H 2 O. The organic layer was separated, concentrated under reduced pressure, purified using silica gel chromatography (0-5% MeOH/CHCl3), and triturated with isopropylether to give (S)-2-((S)-sec- butyl)-5-fluoro-3-oxo-3,4-dihydroquinoxaline-1(2H)-carboxami de (138 mg, 58%) as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 10.72 (s, 1H), 7.28 - 7.24 (m, 1H), 7.05 - 7.01 (m, 2H), 6.49 (s, 2H), 4.50 (d, J = 10.4 Hz, 1H), 1.44 - 1.35 (m, 1H), 1.24 - 1.15 (m, 1H), 1.10 - 1.00 (m, 1H), 0.86 (d, J = 6.7 Hz, 3H), 0.73 (t, J = 7.4 Hz, 3H). LRMS (ESI) m/z 266.3 [M + H] + . [0208] The following compound was prepared by methods analogous to the method described for Compound 100: Example 3: Synthesis of Compound 7 [0209] Step 1: Ethyl (S)-2-((2-bromo-6-nitrophenyl)amino)pentanoate. To a mixture of 1- bromo-2-fluoro-3-nitrobenzene (1.00 g, 4.6 mmol) in DMF (10 mL) was added ethyl (S)-2- aminopentanoate hydrochloride (0.91 g, 5.0 mmol) and DIPEA (2.0 mL, 12.0 mmol). The reaction mixture was heated to 70 °C and stirred overnight. The reaction mixture was cooled to room temperature and quenched with saturated ammonium chloride, extracted with 50% EtOAc/hexane, dried over MgSO4, and concentrated under reduced pressure to give ethyl (S)-2- ((2-bromo-6-nitrophenyl)amino)pentanoate (1.65 g, quantitative) as a brown oil. [0210] Step 2: (S)-5-Bromo-3-propyl-3,4-dihydroquinoxalin-2(1H)-one. To a mixture of ethyl (S)-2-((2-bromo-6-nitrophenyl)amino)pentanoate (1.65 g, 4.8 mmol) in MeOH (20 mL) and water (10 mL) was added Fe powder (1.87 g, 33.5 mmol) and NH4Cl (310 mg, 5.8 mmol) at room temperature. The reaction mixture was heated to 70 ℃ and stirred for 4 h and then heated to 80 °C and stirred overnight. The reaction was cooled to room temperature, diluted with water and CHCl3 and filtered through a Celite pad. The filtrate was extracted with CHCl3, dried over MgSO4, concentrated, and purified using amino silica gel chromatography (0-50% EtOAc/hexane) to give (S)-5-bromo-3-propyl-3,4-dihydroquinoxalin-2(1H)-one (1.04 g, 81%) as a yellow solid. [0211] Step 3: (S)-5-Cyclopropyl-3-propyl-3,4-dihydroquinoxalin-2(1H)-one. To a mixture of (S)-5-bromo-3-propyl-3,4-dihydroquinoxalin-2(1H)-one (265 mg, 0.99 mmol) in toluene (3 mL) and water (800 µL) was added cyclopropylboronic acid (170 mg, 1.99 mmol), potassium phosphate (420 mg, 1.98 mmol), and tetrakis(triphenylphosphine)palladium (60 mg, 0.05 mmol). This mixture was heated to 100 °C and stirred overnight, then cooled to room temperature and diluted with water. Ethyl acetate was added, and the organic layer was separated, dried over MgSO 4 , concentrated, and purified using amino silica gel chromatography (0-50% EtOAc/hexane) and silica gel (0-50% EtOAc/hexane) to give (S)-5-cyclopropyl-3- propyl-3,4-dihydroquinoxalin-2(1H)-one (161 mg, 71%) as a yellow oil. [0212] Step 4: (S)-5-Cyclopropyl-4-(6-methylnicotinoyl)-3-propyl-3,4- dihydroquinoxalin-2(1H)-one. To a solution of 6-methylnicotinic acid (188 mg, 1.4 mmol) in dichloroethane (1.6 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (182 µL, 1.4 mmol). The reaction mixture was stirred for 1 h, and a solution of (S)-5-cyclopropyl-3-propyl- 3,4-dihydroquinoxalin-2(1H)-one (158 mg, 0.7 mmol) in DCE (1.6 mL) and DIPEA (350 µL, 2.04 mmol) was added. This mixture was stirred overnight and then diluted with water and CHCl3. The organic layer was separated, concentrated, and purified using amino silica gel chromatography (0-50% EtOAc/hexane) and reverse phase ODS silica gel chromatography 0- 50% EtOH/H2O), and then triturated with acetonitrile to give (S)-5-cyclopropyl-4-(6- methylnicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2(1H)-one (116 mg) as a colorless solid. LRMS (ESI) m/z 350.4 [M + H] + .
Example 4: Synthesis of Compound 69 [0213] To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (105 mg, 0.8 mmol) in dichloroethane (2.0 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (120 µL, 0.9 mmol). The reaction mixture was stirred for 2 h, and then (S)-5-bromo-3-propyl-3,4- dihydroquinoxalin-2(1H)-one (150 mg, 0.6 mmol) was added, followed by pyridine (135 µL, 1.7 mmol). This mixture was stirred overnight at room temperature, concentrated, and purified using amino silica gel chromatography (0-5% MeOH/CHCl3) and silica gel chromatography (0-5% MeOH/CHCl3) to give (S)-5-bromo-4-(1-methyl-1H-pyrazole-4-carbonyl)-3-propyl-3,4 - dihydroquinoxalin-2(1H)-one (24 mg, 11%) as a colorless solid. 1H NMR (399 MHz, DMSO- d6) δ 10.91 (s, 1H), 7.76 - 7.57 (m, 1H), 7.29 - 7.20 (m, 2H), 7.16 - 7.09 (m, 1H), 6.88 - 6.68 (m, 1H), 5.10 - 4.93 (m, 1H), 3.77 (brs, 3H), 1.53-1.19 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H). LRMS (ESI) m/z 377.1 [M + H] + . [0214] The following compounds were prepared by methods analogous to the method described for Compound 69 (standard protecting group strategies were employed for compounds with reactive heteroatoms): Example 5: Synthesis of Compound 77 [0215] To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (150 mg, 1.2 mmol) in dichloroethane (2.0 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (170 µL, 1.3 mmol). The reaction mixture was stirred for 1 h, and (S)-3-isopropyl-3,4-dihydroquinoxalin- 2(1H)-one (150 mg, 0.8 mmol) was added, followed by pyridine (190 µL, 2.4 mmol). This mixture was stirred overnight and then diluted with water and 20% MeOH/CHCl 3 . The organic layer was separated, concentrated, and purified using amino silica gel chromatography (0-5% MeOH/CHCl3) and silica gel chromatography (0-10% MeOH/CHCl3) to give (S)-3-isopropyl-4- (1-methyl-1H-pyrazole-4-carbonyl)-3,4-dihydroquinoxalin-2(1H )-one (29 mg, 12%) as a colorless solid. 1H NMR (399 MHz, DMSO-d6) δ 10.76 (s, 1H), 7.78 (s, 1H), 7.20 (dt, J = 1.3, 7.6 Hz, 1H), 7.07 - 7.01 (m, 3H), 6.89 (dt, J = 1.3, 7.7 Hz, 1H), 4.59 (d, J = 10.1 Hz, 1H), 3.77 (s, 3H), 1.58 - 1.49 (m, 1H), 0.96 (d, J = 6.7 Hz, 3H), 0.84 (d, J = 6.7 Hz, 3H). LRMS (ESI) m/z 299.2 [M + H] + . Example 6: Synthesis of Compound 63 [0216] To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (140 mg, 1.1 mmol) in dichloroethane (2 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (160 µL, 1.2 mmol). The reaction mixture was stirred for 2 h at room temperature, and a solution of (S)-3-((S)- sec-butyl)-3,4-dihydroquinoxalin-2(1H)-one (150 mg, 0.7 mmol) in CH 2 Cl 2 (2.0 mL) and pyridine (178 µL, 2.2 mmol) was added. This mixture was stirred at room temperature overnight and then diluted with water and CHCl3. The organic layer was separated, concentrated, and purified using amino silica gel chromatography (0-5% MeOH/CHCl 3 ), and triturated with isopropyl ether/hexanes to give (S)-3-((S)-sec-butyl)-4-(1-methyl-1H-pyrazole-4-carbonyl)-3, 4- dihydroquinoxalin-2(1H)-one (130 mg, 57%) as a colorless solid. 1 H NMR (500 MHz, DMSO- d6) δ 10.77 (s, 1H), 7.75 (s, 1H), 7.20 (dt, J = 1.3, 7.7 Hz, 1H), 7.05 (dd, J = 1.2, 8.0 Hz, 1H), 7.03 - 6.99 (m, 2H), 6.89 (dt, J = 1.2, 7.7 Hz, 1H), 4.68 (d, J = 10.1 Hz, 1H), 3.76 (s, 3H), 1.49 - 1.40 (m, 1H), 1.38 - 1.30 (m, 1H), 1.14 - 1.05 (m, 1H), 0.89 (d, J = 6.8 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H). LRMS (ESI) m/z 313.2 [M + H] + . Example 7: Synthesis of Compound 81 [0217] To a solution of 1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (180 mg, 1.2 mmol) in dichloroethane (3 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (250 µL, 1.9 mmol). The reaction mixture was stirred for 1 h at room temperature, and then (S)-3-propyl- 3,4-dihydroquinoxalin-2(1H)-one (200 mg, 1.1 mmol) and pyridine (260 µL, 3.2 mmol) were added. This mixture was stirred for 3 h, concentrated, and purified using silica gel chromatography (0-10% MeOH/CHCl3), purified again using silica gel chromatography (0-75% EtOAc/CHCl3), and triturated using isopropyl ether to give (S)-3-isopropyl-4-(1-methyl-6-oxo- 1,6-dihydropyridine-3-carbonyl)-3,4-dihydroquinoxalin-2(1H)- one (281 mg, 82%) as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 10.79 (s, 1H), 8.10 (d, J = 2.5 Hz, 1H), 7.14 (dt, J = 1.5, 7.5 Hz, 1H), 7.03 (dd, J = 1.2, 8.0 Hz, 1H), 6.91 (dd, J = 1.0, 7.9 Hz, 1H), 6.87 (dd, J = 1.3, 7.2 Hz, 1H), 6.84 (dd, J = 2.6, 9.5 Hz, 1H), 6.11 (d, J = 9.5 Hz, 1H), 4.56 (d, J = 10.0 Hz, 1H), 3.31 (s, 3H), 1.60 - 1.52 (m, 1H), 0.96 (d, J = 6.7 Hz, 3H), 0.85 (d, J = 6.7 Hz, 3H). LRMS (ESI) m/z 326.1 [M + H] + . Example 8: Synthesis of Compound 99 [0218] To an ice-cooled solution of (S)-3-((S)-sec-butyl)-3,4-dihydroquinoxalin-2(1H)-one (685 mg, 3.4 mmol) in THF (7 mL) was added triphosgene (400 mg, 1.4 mmol). After stirring for 30 min, 7 M NH3/MeOH (2 mL, 14 mmol) was added to the reaction mixture. The reaction mixture stirred for 30 min at ice-bath temperature, and was then quenched with water, and extracted with chloroform. The organic layer was separated, dried over MgSO 4 , concentrated, and purified using silica gel chromatography (0-10% MeOH/CHCl3) to give (S)-2-((S)-sec- butyl)-3-oxo-3,4-dihydroquinoxaline-1(2H)-carboxamide (549 mg, 66%) as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.40 (dd, J = 1.2, 8.0 Hz, 1H), 7.10 (dt, J = 1.4, 7.7 Hz, 1H), 7.01 (dt, J = 1.5, 7.7 Hz, 1H), 6.94 (dd, J = 1.4, 7.8 Hz, 1H), 6.35 (s, 2H), 4.50 (d, J = 10.1 Hz, 1H), 1.44 - 1.36 (m, 1H), 1.24 - 1.15 (m, 1H), 1.09 - 1.00 (m, 1H), 0.85 (d, J = 6.7 Hz, 3H), 0.73 (t, J = 7.5 Hz, 3H). LRMS (ESI) m/z 248.2 [M + H] + . Example 9: Synthesis of Compound 132 [0219] To a solution of (S)-3-((S)-sec-butyl)-3,4-dihydroquinoxalin-2(1H)-one (250 mg, 1.2 mmol) in THF (3 mL) was added DIPEA (0.2 mL, 1.2 mmol) and triphosgene (145 mg, 0.5 mmol). After stirring at room temperature for 30 min, this solution was added to a mixture of (1r,3r)-3-aminocyclobutan-1-ol (225 mg, 1.82 mmol), DIPEA (0.42 mL, 0.25 mmol), and THF (3 mL). The reaction mixture was stirred at room temperature overnight, quenched with water, and extracted with chloroform. The organic layer was separated, concentrated, and purified using silica gel chromatography (0-10% MeOH/CHCl3) to give the crude product. The crude product was triturated with IPA and collected to yield pure (S)-2-((S)-sec-butyl)-N-((1R,3S)-3- hydroxycyclobutyl)-3-oxo-3,4-dihydroquinoxaline-1(2H)-carbox amide (211 mg, 54%) as a colorless solid. 1H NMR (500 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.36 (dd, J = 1.1, 8.0 Hz, 1H), 7.09 (dt, J = 1.4, 7.6 Hz, 1H), 7.02 (dt, J = 1.5, 7.7 Hz, 1H), 6.95 (dd, J = 1.5, 7.8 Hz, 1H), 6.75 (d, J = 6.7 Hz, 1H), 4.88 (d, J = 5.2 Hz, 1H), 4.46 (d, J = 10.0 Hz, 1H), 4.27 - 4.15 (m, 2H), 2.24 - 2.18 (m, 1H), 2.15 - 2.08 (m, 1H), 2.08 - 1.99 (m, 2H), 1.43 - 1.34 (m, 1H), 1.24 - 1.15 (m, 1H), 1.08 - 0.99 (m, 1H), 0.84 (d, J = 6.7 Hz, 3H), 0.72 (t, J = 7.4 Hz, 3H). LRMS (ESI) m/z 318.3 [M + H] + . [0220] The following compounds were prepared by methods analogous to the method described for Compound 132:
Example 10: Synthesis of Compound 92 [0221] Step 1: Methyl (3-nitropyridin-2-yl)-L-isoleucinate. To a 100-mL round bottom flask was added 2-fluoro-3-nitropyridine (5.0 g, 35.2 mmol), 2,6-lutidine (10.2 mL, 88.0 mmol), methyl L-isoleucinate (12.8 g, 70.4 mmol) and DMF (50 mL). The reaction mixture was stirred for 4 d, followed by dilution with water (300 mL) and extracted with Et2O (4x100 mL). The organic layers were combined, dried over sodium sulfate, filtered through a pad of celite, and concentrated to give 9.5 g of methyl (3-nitropyridin-2-yl)-L-isoleucinate as a bright yellow oil. [0222] Step 2: (S)-3-((S)-sec-Butyl)-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)- one. Iron powder (9.4 g) was added to a stirring solution of methyl (3-fluoro-2-nitrophenyl)-L-isoleucinate (9.00 g, 33.6 mmol) in AcOH (100 mL) at room temperature. After 2h, the reaction was filtered through a pad of celite, concentrated, and azeotroped with cyclohexane (100 mL) and toluene (100 mL) to give (S)-3-((S)-sec-butyl)-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)- one as a red solid. [0223] Step 3: (S)-3-((S)-sec-Butyl)-4-(1-methyl-6-oxo-1,6-dihydropyridine- 3-carbonyl)- 3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one. Thionyl chloride (0.87 g, 7.3 mmol) was added to a stirring solution of 1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (560 mg, 3.7 mmol), DMF (1 drop), and CH 2 Cl 2 (10 mL) at room temperature. After 2 h, the reaction was concentrated, followed by the sequential addition of NMP (5 mL), (S)-3-((S)-sec-butyl)-3,4- dihydropyrido[2,3-b]pyrazin-2(1H)-one (250 mg, 1.2 mmol), and DIPEA (0.48 g, 3.7 mmol). The reaction stirred for 2 h, quenched with MeOH (10 mL), and stirred for 5 min. The mixture was concentrated, filtered through a 0.4 µm syringe filter, and purified using reverse phase HPLC (0-30% MeCN/H 2 O w/ 0.1% formic acid) to give 115 mg of (S)-3-((S)-sec-butyl)-4-(1-methyl-6- oxo-1,6-dihydropyridine-3-carbonyl)-3,4-dihydropyrido[2,3-b] pyrazin-2(1H)-one as a white solid. 1H NMR (400 MHz, Methanol-d4) δ 7.90 (d, J = 2.6 Hz, 1H), 7.76 (dd, J = 4.9, 1.6 Hz, 1H), 7.33 (dd, J = 7.9, 1.6 Hz, 1H), 7.12 (dd, J = 8.0, 4.9 Hz, 1H), 6.86 (dd, J = 9.4, 2.6 Hz, 1H), 6.13 (d, J = 9.5 Hz, 1H), 4.78 (s, 1H), 3.44 (s, 3H), 1.58 – 1.32 (m, 2H), 1.31 – 1.02 (m, 2H), 0.86 (d, J = 6.7 Hz, 3H), 0.75 (t, J = 7.4 Hz, 3H). LRMS (APCI) m/z 341.0 [M + H] + . [0224] The following compounds were prepared by methods analogous to the method described for Compound 92: Example 11: Synthesis of Compound 94 [0225] Step 1: Methyl (2-chloro-5-nitropyrimidin-4-yl)-L-isoleucinate. Methyl L- isoleucinate (5.8 g, 32.2 mmol) was slowly added to a stirring solution of 2-chloro-4-fluoro-5- nitropyrimidine (5.0 g, 25.8 mmol), DIPEA (13.5 mL, 77.3 mmol), and DMF (50 mL). After 30 min, the reaction was poured into water (300 mL) and extracted with Et 2 O (4x100 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified using silica gel chromatography (0-15% EtOAc/hexanes) to give 2.75 g of methyl (2-chloro-5- nitropyrimidin-4-yl)-L-isoleucinate as a yellow oil. [0226] Step 2: (S)-7-((S)-sec-butyl)-7,8-dihydropteridin-6(5H)-one. Methyl (2-chloro-5- nitropyrimidin-4-yl)-L-isoleucinate, Pearlman’s catalyst, and MeOH (50 mL) were mixed and stirred under a hydrogen atmosphere (80 psi) at room temperature for 4 h. The reaction was then filtered through a pad of celite and concentrated. Acetic acid was added, and the mixture was heated to 100 °C and stirred for 2 h. The reaction was then cooled to room temperature, concentrated, suspended in 10% MeOH/CH2Cl2, and filtered through a pad of silica to give 1.5 g of (S)-7-((S)-sec-butyl)-7,8-dihydropteridin-6(5H)-one. [0227] Step 3: (S)-7-((S)-sec-butyl)-8-(1-methyl-1H-pyrazole-4-carbonyl)-7, 8- dihydropteridin-6(5H)-one. Thionyl chloride (0.58 g, 4.8 mmol) was added to a stirring solution of 1-methyl-1H-pyrazole-4-carboxylic acid (0.46 g, 3.6 mmol), DMF (1 drop), and CH 2 Cl 2 (10 mL) at room temperature. After 2 h, the reaction was concentrated, followed by the sequential addition of NMP (2 mL), (S)-7-((S)-sec-butyl)-7,8-dihydropteridin-6(5H)-one (250 mg, 1.2 mmol), and DIPEA (0.8 g, 6.1 mmol). The reaction stirred for 4 h, quenched with a methylamine/MeOH solution, and stirred for 5 min. The mixture was concentrated, filtered through a 0.4 µm syringe filter, and purified using reverse phase HPLC (0-30% MeCN/H 2 O w/ 0.1% formic acid) to give 55 mg of (S)-7-((S)-sec-butyl)-8-(1-methyl-1H-pyrazole-4-carbonyl)- 7,8-dihydropteridin-6(5H)-one as a white solid. 1H NMR (400 MHz, Methanol-d4) δ 8.35 (s, 1H), 8.26 (s, 1H), 7.72 (s, 1H), 7.25 (s, 1H), 4.73 (s, 1H), 3.74 (s, 3H), 1.50 (tq, J = 10.3, 4.2, 2.9 Hz, 2H), 1.14 (ddt, J = 15.9, 8.5, 4.3 Hz, 1H), 0.83 (d, J = 6.5 Hz, 3H), 0.78 (t, J = 7.2 Hz, 3H). LRMS (APCI) m/z 315.0 [M + H] + . [0228] Compound 125 was prepared by using an analogous method: Example 12: Synthesis of Compound 95 [0229] To a stirring solution of 1-methyl-1H-pyrazole-4-carbonyl chloride (0.63 g, 4.4 mmol) was added a mixture of (S)-2-((S)-sec-butyl)-1,4-dihydropyrido[2,3-b]pyrazin-3(2H)- one (300 mg, 1.5 mmol), DIPEA (0.8 mL, 5.8 mmol), DMAP (18 mg, 0.1 mmol), and NMP (5 mL). The reaction was stirred for 2 h at room temperature, quenched with methylamine/MeOH, and stirred for 5 min. The mixture was concentrated, filtered through a 0.4 µm syringe filter, and purified using reverse phase HPLC (0-30% MeCN/H2O w/ 0.1% formic acid) to give (S)-2-((S)- sec-butyl)-1-(1-methyl-1H-pyrazole-4-carbonyl)-1,4-dihydropy rido[2,3-b]pyrazin-3(2H)-one as a white solid. 1H NMR (400 MHz, Methanol-d4) δ 8.09 (dd, J = 4.9, 1.4 Hz, 1H), 7.64 (s, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.19 (s, 1H), 6.87 (dd, J = 8.0, 4.9 Hz, 1H), 4.79 (d, J = 9.6 Hz, 1H), 3.74 (s, 3H), 1.46 (dqd, J = 15.0, 7.5, 3.7 Hz, 1H), 1.35 (tdd, J = 9.7, 6.4, 3.2 Hz, 1H), 1.19 – 1.00 (m, 1H), 0.89 (d, J = 6.7 Hz, 3H), 0.75 (t, J = 7.4 Hz, 3H). LRMS (APCI) m/z 314.0 [M + H] + .
Example 13: Synthesis of Compounds 27-29 and 33-44 [0230] The following compounds were prepared by nucleophilic aromatic substitution (SNAr) by reacting (S)-4-(6-fluoronicotinoyl)-3-propyl-3,4-dihydroquinoxalin-2( 1H)-one with the appropriate amine:
[0231] Additional compounds can be prepared by nucleophilic aromatic substitution (SNAr) by reacting the appropriate fluoroaryl or fluoroheteroaryl intermediate with the appropriate amine. The reaction can be conducted in the presence of quantitative or excess amine at elevated temperatures, for example >100 °C, using a polar aprotic solvent such as NMP, DMSO, DMF, dioxanes, THF, or no solvent at all. Biological Example 1 Assay Example 1: Preparation and assay of fast skeletal myofibrils [0232] Preparation of fast skeletal myofibrils: Rabbit skeletal myofibrils were prepared based upon the method of Herrmann et al. (Biochem. 32(28):7255-7263(1993). Myofibrils were prepared from rabbit psoas muscle purchased from Pel-Freez Biologicals (Arkansas) within 2 days of ordering, stored on ice. Minced muscle was homogenized in 10 volumes of ice-cold “standard” buffer (50 mM Tris, pH 7.4, 0.1 M KOAc, 5 mM KCl, 2 mM dithiothreitol (DTT), 0.2 mM phenylmethylsulfonyl fluoride (PMSF), 10 µM leupeptin, 5 µM pepstatin, and 0.5 mM sodium azide) containing 5 mM ethylenediaminetetraacetic acid (EDTA) and 0.5% Triton X-100 using an Omni-Macro homogenizer. Myofibrils were recovered by low speed centrifugation (3000 rpm for 10 minutes) and washed 2 times in the Triton X-100 containing buffer to ensure removal of cellular membrane. Following the Triton washes, myofibrils were washed 3 times in “standard” buffer containing 2 mM magnesium acetate. A final wash in assay buffer (12 mM piperazine-1,4-bis(2-ethanesulfonic acid) (PIPES), pH 6.8, 60 mM KCl, 1 mM DTT) was performed and brought to 10% sucrose for flash freezing in liquid nitrogen and storage at -80°C. [0233] Activation of Fast Skeletal Myofibrils: Fast fiber activators were identified by measuring the enzymatic activity of muscle myofibril preparations using the proprietary PUMA (trademark) (see, e.g., U.S. Patent Nos. 6,410,254, 6,743,599, 7,202,051, and 7,378,254) assay system. Myofibril preparations consisted of rabbit skeletal muscle (approximately 90% fast fibers) that had been mechanically homogenized and washed with a detergent (Triton X-100) to remove cellular membranes. This preparation retained all of the sarcomeric components in a native conformation and the enzymatic activity was still regulated by calcium. Compounds were tested using a myofibril suspension and a level of calcium sufficient to increase enzymatic activity of the myofibrils to 25% of their maximal rate (termed pCa25). Enzymatic activity was tracked via a pyruvate kinase and lactate dehydrogenase-coupled enzyme system. This assay regenerates myosin-produced ADP into ATP by oxidizing NADH, producing an absorbance change at 340 nm. The buffering system was 12 mM PIPES, 2 mM MgCl2, 1 mM DTT at pH 6.8 (PM12 buffer). Data were reported as AC1.4, which is the concentration at which the compound increased the enzymatic activity by 40%. In Table 3, “Example Compound” refers to the compound labeled with the same number in Table 2. Table 3
Assay Example 2: Preparation and assay of rat isometric ankle plantarflexor muscle force [0234] Female Sprague Dawley rats were placed under a stable anesthesic plane with inhaled isoflurane (1-5%). One incision was made on the mid-thigh region of the right leg to expose the sciatic nerve. To prevent co-contraction of the ankle dorsiflexors, an additional incision was made lateral to the patella to isolate and sever the peroneal nerve. Rats were then placed on a temperature-maintained in situ muscle analysis rig (Aurora Scientific, Model 806C). The knee was immobilized in a clamp between two sharpened screws and the foot was taped to a footplate attached to a force transducer (Aurora Scientific, Ontario, Canada). Stainless steel needle electrodes (0.10 mm) were hooked around the exposed sciatic nerve. Isometric ankle plantarflexor muscle contractile force was assessed with the ankle joint at 90° flexion. A 30 Hz electrical stimulation (under supramaximal voltage conditions) was applied to the nerve and the resulting muscle force was recorded via a servomotor. A pre-dose 30Hz force response was established as the baseline force. A pre-dose 150 Hz force response was established as the maximum isometric force. Compounds were formulated in 50% polyethylene glycol (PEG): 16% Cavitron: 10% dimethylacetamide (DMA) and administered by continuous intravenous infusion over a sixty minute period. The muscle force response to compound was measured every two minutes over the dosing period. Data were reported as an estimated EC50 value, which is the concentration at which muscle force is 50% of the pre-dose maximum tension. The EC 50 results are summarized in Table 4 below. In Table 4, “Example Compound” refers to the compound labeled with the same number in Table 2. Table 4