CLAIMS

What is claimed is:

1. A compound represented by the following structural formula (I):

wherein R is: a) hydrogen; b) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₂ -C ₃ )alkenyl, (C ₃ -C ₇ )cycloalkyl(C ₂ - C ₃ )alkynyl, (C ₁ -C ₈ )alkoxy, (C ₃ -C ₈ )alkenyloxy, (C ₃ -Cs)alkynyloxy, (C ₃ -C ₇ )cycloalkoxy, (C ₅ -C ₇ )cycloalkenyloxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyt, (C ₃ -C ₇ )cycIoalkyl(C ₁ -C ₃ )alkoxy,

(C ₅ -C ₇ )cycloalkenyl(C ₁ -C ₃ )alkoxy, (C ₁ -C ₈ )alkylthio, (C ₃ -C ₈ )alkenylthio _! (C ₃ - C ₈ )alkynylthio, (C ₃ -C ₇ )cycloalkylthio(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkylthio, (C ₅ - C ₇ )cycloalkenyl(C ₁ -C ₃ )alkylthio, (C ₁ -C ₈ )alkylamino, di(C ₁ -C ₈ )aIkylamino, azepano, azetidino, piperidino, pyrrolidine, (C ₃ -C ₇ )cyc)oalky)amino, ((C ₃ -C ₇ )cycIoalkyl(C ₁ - C ₃ )alkyl)amino, or tri(C ₁ -C ₄ )alkylsilyl, each optionally and independently substituted with zero to four substituents selected from the group consisting of halogen, hydroxy, (C _t - C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )cycloalkoxy and oxo; c) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, aryl(C ₁ -C))alkoxy, heteroaryl(C ₁ -C ₃ )aIkoxy, aryl(C ₂ -C ₃ ))alkenyl, aryl(C ₂ -C ₃ )alkynyl, heteroaryl(C ₂ -C ₃ )alkenyl, or heteroaryl(C ₂ -C ₃ )a3kynyl, each optionally and independently substituted with zero to three substituents selected from the group consisting of: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ - . C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )-cycloalkyl(C ₂ -C ₄ )alkynyI, halo(C ₁ -C6)alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, . (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycloalkoxy, halo(C ₄ -

C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ -C ₇ )cycloalkylalkylthio, haIo(C ₁ -C ₆ )alkylthio, haIo(C ₃ -C ₆ )cycloalkythio, halo(C ₄ -C ₇ )cycloalkylalkylthio, (C ₁ - C ₆ )alkanesulfinyl, (C ₃ -C ₆ )cycloalkanesulfinyl, (C|-C ₇ )cycloalkylalkanesulfinyl, halo(C _t - C ₆ )alkanesulFιnyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, haIo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ -C ₇ )cyclo- alkylalkanesulfonyl, (C ₁ -C ₆ )aIkylamino, di(C ₁ -C ₆ )alkylamino, (C ₁ -C _fi )alkoxy(C ₁ - C ₆ )alkoxy, haIo(C ₁ -C ₆ )alkoxy(C _r -C ₆ )alkoxy, (C ₁ -Cajalkoxycarbonyl, H ₂ NCO, H ₂ NSO ₂ , (C ₁ -Cβ)alkylaminocarbonyl, and di(C ₁ -C ₆ )alkylaminocarbonyl, (C ₁ -C ₆ )alkylaminosulfonyl, and di(C ₁ -C ₆ )alkylaminosulfonyl; or

d) a divalent radical selected from -(CH ₂ ) ₃ -, -(CHa) ₄ -, -(CH ₂ ) ₅ - or -(CH ₂ V, which is attached to

R ¹ to form a fused or spirofused ring system, and is optionally and independently substituted with zero to four substituents selected from: halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ - C ₆ )alkyl, (C ₁ -C ₆ )alkoxy and oxo;

R ¹ is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-1 ,3-dioxole, benzo-I ,3-dioxιne, 2,3-dihydrobenzo-l,4-dioxine or (C ₃ -C ₇ )cycloalkyl, each optionally and independently substituted with zero to four substituents selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -Q)alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ - C ₆ )alkynyl, (C ₃ -C ₆ )-cycloalkyl(C ₂ -C ₄ )alkynyI, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkyIalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, ha!o(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycloalkoxy, halo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ - C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkythio, halo(C ₄ -C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ - C ₆ )cycloalkanesulfinyl, (C ₄ -C ₇ )cycloalkylalkanesulfinyl, halo(C ₁ -C _ή )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyl, (Q - C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, HaIo(Cp C ₆ )alkanesulfonyl, halo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ -C ₇ )cycloalkylaIkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, halo(C[- C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, H ₂ NSO ₂ , H ₂ NCO, (C ₁ -

C _f i)alkylaminosulfonyl, di(C ₁ -C ₆ )alkylaminosuIfonyl, (C ₁ -C ₆ )alkylaminocarbonyl and di(C ₁ -C ₆ )alkylaminocarbonyl;

X and Y are each independently CH ₂ or a single bond;

R ² is: a) -H; or b) (C ₁ -C ₁₂ )alkyl, (C ₂ -C ₁₂ )alkenyl, (C ₂ -C ₁₂ )alkynyl, (C ₁ -C ₁₂ )alkoxy, (C ₁ -C ₁₂ )alkylthio, (C ₁ - C ₁₂ )alkylamino, oxo(C ₁ -C ₁₂ )alkyl, oxo(C ₂ -C ₁₂ )alkenyl, oxo(C ₂ -C ₁₂ )alkynyl, oxo(C ₁ - C ₁₂ )alkoxy, oxo(C ₁ -C ₁₂ )alkylthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl _J

(C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )aIkyIamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkyithio, (C ₁ - C ₆ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkylamino, (C _| -C ₄ )aIkoxy(C ₁ -C ₄ )alkoxy(C ₁ -C ₄ )alkyl, aminocarbonylamino(C ₁ -

C ₁₂ )alkyl, aminocarbonylamino(C ₁ -C ₁ ^alkoxy, aminocarbonylamino(C ₁ -C ₁₂ )alkylthio, aminocarbonylamino(C ₁ -C ₁ a)alkylamino, (C ₁ -C ₆ )alkanoylamino(C ₁ -C _fi )aIkyl, (C ₁ - C ₆ )alkanoylamino(C ₁ -C ₆ )alkoxy _J (C ₁ -C ₆ )alkanoylamino(C ₁ -C ₆ )alkylthio, (C ₁ -

C ₁₅ )alkanoylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkoxycarbonyI(C ₁ -C ₆ )aIkoxy, (C ₁ -C ₆ )aIkoxycarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )aIkoxycarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C6)acyloxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ ) acyloxy(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkylamino, aminosulfonylamino(C ₁ -C ₁₂ )alkyl, aminosulfonylamino(C ₁ -C ₁₂ )alkoxy, aminosulfonyIamino(C ₁ -C ₁₂ )alkylthio, aminosulfonylamino(C ₁ -C ₁₂ )alkylamino, (C _t - C ₆ )alkanesuIfonylamino(C ₁ -C6)alkyI, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C6)alkoxy, (C ₁ - C$)alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkanesulfonyIamino(C ₁ -C ₆ )alkylamino, formylamino(C ₁ -C ₆ )alkyl, formylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ -C ₆ )alkylthio, formylamino(C ₁ -C ₆ )alkylamino, (C ₁ .-C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkyl, (C ₁ -

C ₆ )aIkoxycarbonylamino(C ₁ -C ₆ )aIkoxy, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )aIkoxycarbonylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkylaminocarbony1amino(C ₁ -C ₆ )alkylamino, aminocarbonyl(C ₁ - C ₆ )alkyl, aminocarbonyI(C ₁ -C ₆ )alkoxy, aminocarbonyl(C ₁ -C ₆ )aIkylthio, aminocarbonyI(C ₁ -C ₆ )aIkylamino, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )aIkoxy, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyamino, aminocarboxy(C ₁ -C ₆ )alkyl, aminocarboxy(C ₁ - C ₆ )alkoxy, aminocarboxy(C ₁ -C ₆ )alkylthio, aminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ - C ₆ )alkylaminocarboxy(C ₁ -C ₆ )aIkyl, (C ₁ -C _fi )alkylaminocarboxy(C ₁ -C6)alkoxy, (Cp

Cβ)alkylaminocarboxy(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkyIaminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ - C ₁₂ )alkoxycarbonylamino, (C ₁ -C ₁₂ )alkylaminocarbonylamino, or (C ₁ -C ₁₂ )aIkanoylamino, each optionally substituted by: 1) 1 to 5 halogen atoms; and/or 2) 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -

C ₆ )cycloalkyl ₁ (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, haIo(C ₁ -C ₃ )alkoxy, halo(C ₃ - C ₆ )cycloalkyl, and ha!o(C ₃ -C _fi )cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to a thiocarbonyl groups;

R ³ is hydrogen, halogen, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkoxy, hydroxyl, hydroxy(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino, (C ₁ -C ₆ )alkoxycarbonylamino, (C ₁ - C6)alkylaminocarbonylamino, di(C ₁ -C6)alkylaminocarbonylamino, (C ₁ - C ₆ )alkanesulfonylamino, (C ₁ -C ₆ )alkylaminosulfonylamino, di(C ₁ -

C ₆ )alkylaminosulfonylamino, phenylamino or heteroarylamino in which each phenylamino or heteroarylamino group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -

C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -Q)- cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ - C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )CyClOaIkOXy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycloalkoxy, halo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ - C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkylthio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloaIkylthio, haIo(C ₄ -C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )aIkanesulfinyI, (C ₃ - C ₆ )cycloalkanesulfinyl, (C ₄ -C^cycloalkylalkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfιnyl, ha]o(C ₄ -C ₇ )cycloaIkylalkanesulfιnyl, (C ₁ - C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ - C ₆ )alkanesulfonyl, haIo(C ₃ -C ₆ )cycloalkanesulfonyl, haIo(C ₄ -C ₇ )cycloalkylalkanesuIfonyl,

(C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )aIkylamino, (C ₁ -C ₆ )alkoxy(C _l -C ₆ )alkoxy, halo(C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C _f i)alkoxycarbonyl, aminocarbonyl, (C ₁ - C ₆ )alkytaminocarbonyl, and di(C ₁ -C ₆ )alkylaminocarbonyl; provided that: i) R ² and R ³ are not both hydrogen; and ii) when R ³ is hydroxy, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ -C _{1 2} )alkoxy, (C ₁ -C^alkylthio, (C ₁ -C ₁ -)alkylamino, oxo(C ₁ -C ₁₂ )alkoxy, oxo(C ₁ -C _{] 2} )aIkyIthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )aIkoxy(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkylamino, (C ₁ -C ₃ )alkylthio(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio(C ₁ -

C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkylthio ₃ (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )aIkylthio, (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkylamino, aminocarbonylamino(C ₁ -C ₁₂ )alkoxy, aminocarbonylamino(C ₁ - C ₁₂ )alkylthio, aminocarbonylamino(C ₁ -C ₁₂ )alkyIamino, (C ₁ -C ₆ )alkanoylamino(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkanoyIamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkanoylamino(C ₁ -

C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkyIamino, (C ₁ -C ₆ ) acyloxy(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₆ )alkylthio _s (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkylamino, aminosulfonylamino(C ₁ -C ₁₂ )alkoxy, aminosulfonylamino(C ₁ -C ₁₂ )alkylthio, aminosulfonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )aIkyIamino, formylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ -C ₆ )alkylthio, formylamino(C ₁ -C ₆ )alkylamino, (C ₁ - C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkoxycarbonyIamino(C ₁ -C ₆ )alkylamino, (C ₁ -

C ₆ )alkylaminocarboήylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkylamino, aminocarbonyl(C ₁ -C ₆ )alkoxy, aminocarbonyl(C ₁ -C6)alkylthio, aminocarbonyl(C ₁ -

QOalkylamino, (C ₁ -C ₆ )alkylaminocarbonyI(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ - Ca)alkylamino, aminocarboxy(C ₁ -C ₆ )aIkoxy, aminocarboxy(C ₁ -C ₆ )alkyIthio, aminocarboxy(C ₁ -C _fi )alkylamino, (C ₁ -C ₆ )alkyIaminocarboxy(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkyIaminocarboxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ -

^• C ₆ )alkylamino, (C ₁ -C ₁₂ )alkoxycarbonylamino, (C ₁ -C ₁₂ )alkylaminocarbonylamino, or (C ₁ -C ₁₂ )alkanoylamino, each optionally substituted by:

1 ) I to 5 halogen atoms; and/or

2) 1 group selected from cyano, hydroxy, (C ₁ -C ₃ )alkyI, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ^' ₃ -C ₆ )cycloalkyI, or halo(C ₃ -C ₆ )cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to thiocarbonyl groups;

A 'is a saturated or unsaturated 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ ) _m via bonds to two members of said ring, wherein said ring is composed of carbon atoms and 0-2 hetero atoms selected from the group consisting of 0, 1 , or 2 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally and independently substituted with zero to four halogen atoms, (C ₁ -C ₆ )alkyl groups, halo(C ₁ -C ₆ )alkyl groups or oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively;

m is 1 to 3;

Q and Y are attached to carbon or nitrogen atoms in ring A in a 1 ,2-, 1 ,3-, or 1 ,4- relationship;

Q is a divalent radical selected from

W is a bond or a (C ₁ -Cβ) alkylene; and

W is optionally and independently substituted by zero to four groups selected from: 1) (C ₁ -C ₁₂ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₃ -QOcycloaJkyl(C-C ₃ )alkyl, (C ₂ -C ₁₂ )alkenyl,

(C ₅ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkenyl, (C ₂ -C ₁₂ )alkynyl, (C ₃ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkynyl, (C ₄ - C _{1 2} )bicycloalkyl(C ₁ -C ₃ )alkyl, (C ₈ -C _H )tricycloalkyl(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )aIkyIthio(C ₁ -C ₆ )alkyI, (C ₃ - C ₈ )cycloalkylthio(C ₁ -C ₃ )alkyl, saturated heterocyclyl, saturated heterocyclyl(C ₁ -C ₃ )alkyl, hydroxy and oxo wherein:

(a) hydrogen atoms in these groups are optionally and independently substituted by zero to six groups selected from: halogen, cyano, hydroxy, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, haIo(C ₁ -C ₃ )alkyI, halo(C ₁ -C ₃ )alkoxy, ha!o(C ₃ - C ₆ )cycloalkyl, haIo(C ₃ -C ₆ )cycIoalkoxy and wherein (b) divalent sulfur atoms are optionally oxidized to sulfoxide or sulfone; or

2) phenyl, naphthyl, heteroaryl, phenyl(C ₁ -C ₃ )alkyl, naphthyl(C ₁ -C ₃ )alkyl, and heteroaryl(C ₁ -C ₃ )alkyl, each optionally and independently substituted with zero to three groups selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cyc]oalkyl, (C ₍ ,-C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )cycloalkyl-(C ₂ - Oalkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -

C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ - C ₆ )cycloalkoxy, halo(C ₄ -C ₇ )cycloalkyIalkoxy, (C ₁ -C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkylthio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkyIthio, HaIo(C ₄ - C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (Cs-C ₆ Jcycloalkanesulfinyl, (C ₄ - C^cycloalkylalkanesulfϊnyl, halo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₃ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, . (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C _fi )alkanesulfonyl, halo(C ₃ - C ₆ )cycloalkanesulfonyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfonyI, (C ₁ -C ₆ )aIkylamino, di(C ₁ - C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )aIkoxy, (C ₁ -

C6)alkoxycarbonyl, aminocarbonyl, (C ₁ -C ₆ )alkylaminocarbonyl, di(C ₁ - C ₆ )alkylaminocarbonyl, cyano(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, carboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C ₆ )alkyl, (C ₄ -C ₈ )cycloaIkylalkoxy(C ₁ - C ₅ )alkyl, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyI, halo(C ₃ -C ₆ )cycloalkoxy(C ₁ -C ₆ )alkyl, halo(C ₄ - C ₈ )cycloalkylalkoxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylthio(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkylthio(C ₁ -

C ₆ )alkyl, (C ₄ -C ₈ )cycIoalkylalkylthio(C ₁ -C ₆ )aIkyl, ha]o(C ₁ -C ₈ )alkylthio(C ₁ -C ₆ )alkyl, haIo(C ₃ -C ₈ )cycloalkylthio(C ₁ -C ₆ )alkyI, halo(C ₄ -C ₈ )cycIoalkylalkyIlhio(C ₁ -C ₆ )alkyI, (C ₁ - C ₈ )alkanesu!f!nyl(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkanesu!fιnyl(C ₁ -C ₆ )alkyl, (C ₄ - C ₈ )cycloalkyIalkanesulfinyl(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₈ )alkanesulfinyl(C ₁ -C ₆ )alkyl, halo(C ₃ - C ₈ )cycloalkanesulfinyl(C ₁ -C ₆ )alkyl, haio(C ₄ -C ₈ )cycloalkylaIkanesulflnyI(C ₁ -C ₃ )alkyI, (C ₁ -

C ₈ )alkanesuIfonyI(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkanesulfonyl(C ₁ -C ₆ )alkyI, (C ₄ -C ₈ ) cycloalkylalkanesulfonyl(C ₁ -C ₆ )aIkyl, halo(C ₁ -C ₈ )alkancsulfonyl(C ₁ -C ₆ )alkyl, halo(C ₃ - C ₈ )cycloalkanesulfonyl(C ₁ -C ₆ )alkyI, halo(C ₄ -C _a )cycloalkylalkanesulfonyI(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylamino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₈ )alkylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkoxycarbonyI(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )acyloxy(C ₁ -C ₆ )alkyl, aminocarbonyl(C ₁ -C ₆ )alkyI,

(C ₁ -C ₈ )alkylaminocarbonyI(C ₁ -C ₆ )alkyl, di(C ₁ -C ₈ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl (C ₁ - C ₈ )acylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkoxycarbonylamino, (C ₁ -C ₃ )alkoxycarbonylamino(C ₁ - C ₆ )alkyl, aminocarboxy(C ₁ -C ₆ )aIkyl, (C ₁ -C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl and di(C ₁ - C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl, phenyl, napthyl, heteroaryl, bicyclic heteroaryl, phenoxy, naphthyloxy, heteroaryloxy, bicyclic heteroaryloxy, phenylthio, naphthylthio, heteroarylthio, bicyclic heteroarylthio, phenylsulfinyl, naphthylsulfinyl, heteroarylsulfinyl, bicyclic heteroarylsulfinyl, phenylsulfonyl, naphthylsulfonyl, heteroarylsulfonyl, bicyclic heteroarylsulfonyl, phenyl(C ₁ -C ₃ )alkyl, napthyl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, and bicyclic heteroaryl(C ₁ -C ₃ )alkyl, wherein the aromatic and heteroaromatic groups are optionally and independently substituted with zero to three groups selected from: halogen, cyano, (C ₁ -C ₃ )alky), halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, ha!o(C ₁ - C ₃ )alkoxy, (C ₁ -C ₃ )alkanesulfonyl, and (C ₁ -C ₃ )alkoxycarbonyl;

E is a saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ J _n via bonds to two members of said ring, wherein said ring is composed of carbon atoms and zero to four hetero atoms selected from: zero to four nitrogen atoms, zero or one oxygen atoms, and zero or one sulfur atoms, said ring being optionally and independently substituted with zero to four groups selected from: halogen, hydroxy, (C ₁ -Cβ)alkyl, (C ₃ - C ₈ )cycloalkyl(C ₁ -C ₆ )alkyI, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, and oxo groups, such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; n is 1 to 3;

G is hydrogen, (C ₁ -C ₆ )alkyl, (C ₄ -C ₇ )heterocyclyl, hydroxy, hydroxy(C ₁ -C ₆ )alkyl, -NR ^4a R ⁴ , -O(C ₁ -C ₆ )aIkyl-NR ^4a R ⁴ , amino(C ₁ -C ₆ )alkylcarboxy, (C ₃ -C ₈ )cycloalkyl, (C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyI, di(C ₁ -C ₆ )alkylamino, di(C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkyl, C(=NH)NH ₂ , C(=NH)NHR ⁴ , NHCf=NH)-NH ₂ ,

NHC(=NH)NHR ⁴ ; -(C ₀ -C ₆ )alkyl-NR ⁴ R ^4a , -NHC(=NH)NRV ^a , -C(=O)(C ₁ -C ₆ )alkyl-NRV ^a , -C(=NH)NR ⁴ R ⁴ \ -C(=O)(C ₁ -C ₄ )alkylaryl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl(C ₃ -C _a )cycloalkyl, or -(C ₁ -C ₄ )aIkyI(C ₄ -C ₇ )heterocycIyl, wherein the (C ₁ -C ₄ )alkyl moiety is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino; and where R ^4a is H or (C ₁ -C ₃ )alkyl and R ⁴ is selected from H, (C ₁ -C ₃ )alkyl,

(C ₃ -C ₇ )cycIoalkyl(C ₁ -C ₅ )alkyl, and (C ₄ -C ₇ )heterocyclyl(C ₁ -C ₆ )alkyl, or R ⁴ and R ⁴ °, taken together with the nitrogen atom to which they arc attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1 -3 heteroatoms selected from 1, 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally • substituted with up to four groups independently selected from halogen, hydroxy, amino,

(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino, halo(C ₁ -C ₆ )alkyI, hydroxy(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl,, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; or an enantiomer, diastereomer or pharmaceutically acceptable salt thereof.

2. The compound of Claim I wherein W is a bond or an unsubstituted (C)-C ₆ ) alkylene group.

3. The compound of any one of Claims 1 or 2 wherein W is an optionally substituted (C ₁ - C ₆ )alkylene group and G is hydrogen, (C ₁ -C ₆ )alkyl, (C ₄ -C ₇ )heterocyclyl, hydroxy, hydroxy(C ₁ -C ₆ )alkyl, -NR ^4a R ⁴ , -O(C ₁ -C ₆ )alkyl-NR ^4a R ⁴ , amino(C ₁ -C ₆ )alkylcarboxy, (C ₃ - C ₈ )cycloalkyl, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₆ )a'kylamino, di(C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyl, C(=NH)NH ₂ , C(=NH)NHR ⁴ , NHC(=NH)NH ₂ , NHC(=NH)NHR ⁴ ; -(Co-C ₆ )alkyl-NR ⁴ R ^4a , -NHC(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₆ )aIkyl-NR ⁴ R ^4a , -C(=NH)NR ⁴ R ^4p , -C(=O)(C ₁ -C ₄ )alkyIaryl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl,

-(C ₁ -C ₄ )alkyl(C ₃ -C ₈ )cycloalkyl, or -(C ₁ -G,)alkyl(C ₄ -C ₇ )heterocyclyl, wherein the (C ₁ -C ₄ )alkyl moiety is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino; or

W is a bond and G is hydrogen, (C ₁ -C ₃ )alkyl, (C ₄ -C ₇ )heterocyclyl, -O(C ₁ -C ₅ )alkyl-NR ^4D R' ¹ , amino(C ₁ -C ₆ )alkylcarboxy, (C ₃ -C ₈ )cycloalkyl, di(C ₁ -C ₆ )alkylamino, di(C ₁ -

C ₆ )alkylamino(C ₁ -C ₆ )alkyl; -(C ₀ -C ₆ )alkyl->JR ⁴ R' ^la , - ^■ NHC(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₆ )alkyI-NR ⁴ R' ^la , -C(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₄ )alkylaryl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl(C ₃ -C ₈ )cycloalkyl, or

-(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, wherein the (C ₁ -C ₄ )alkyl moiety is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino.

4. The compound of any one of Claims 1 or 2 wherein the compound is represented by

Formula II:

wherein: Ring A is a) a benzene ring (A ¹ and A ⁴ are CH and the bonds in ring A are aromatic bonds); b) piperidine (A ¹ is N, A ⁴ is CH ₂ and the bonds in ring A are single bonds); or c) morpholine (A ¹ is N, A ⁴ is O and the bonds in ring A are single bonds); or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

5. The compound of claim 4 wherein the compound is represented by Formula IIa:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

6. The compound of Claim 4 wherein the compound is represented by Formula Hb:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

7. The compound of Claim 4 wherein the compound is represented by Formula Uc:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

8. _ The compound of Claim 4 wherein the compound is represented by Formula III:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

9. The compound of Claim 8 wherein the compound is represented by Formula IIIa:

I O or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

10. The compound of Claim 8 wherein the compound is represented by Formula 1Hb:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

1 1. The compound of Claim 8 wherein the compound is represented by Formula IMc:

or an enantiomer, diastereomer, or pharmaceutically acceptable sail thereof.

12. The compound of Claim 4 wherein the compound is represented by Formula IV:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

13. The compound of Claim 12 whereing the compound is represented by Formula IVa:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

14. The compound of Claim 12 wherein the compound is represented by Formula IVb:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

15. The compound of Claim 12 wherein the compound is represented by Formula IVc:

or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

16. A compound according to any one of Claims 4 through 15 wherein: R is a) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₃ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₃ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycIoalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₂ -C ₃ )alkenyl, (C ₃ -C ₇ )cycloalkyl(C ₂ - C ₃ )alkynyl, (C ₁ -C ₈ ) alkoxy, (C ₃ -C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ - C ₇ )cycIoalkyl(C ₁ -C ₃ )alkoxy, (C ₁ -C ₈ )alkylthio, (C ₃ -C ₇ )cycloalkylthio, (C ₃ - C ₇ )cycloalkylthio(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkylthio, azepano, azetidino, piperidino, pyrrolidino or tri(C ₁ -Q)aIkylsilyl, each optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C ₁ - C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )cycloalkoxy, and oxo; or b) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, aryl(C ₁ -C ₃ )alkoxy, heteroaryl(C _| -C ₃ )alkoxy, arylethenyl, heteroarylethenyl, or arylethynyl, heteroarylethynyl, each optionally substituted with up to three substituents independently selected from the group consisting of: halogen, (C ₁ -C ₆ )alkyl, (C ₃ - C ₆ )cycloalkyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -

Q)cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkanesulfinyl, halo(C ₁ -C ₆ )alkancsulfinyl, (C ₁ -C ₆ )alkanesulfonyl, haIo(C ₁ -C ₆ )alkanesulfonyl, H ₂ NCO, H ₂ NSO ₂ , (C ₁ -C ₆ )alkylaminocarbonyl, and (C ₁ - C ₆ )alkylaminosulfonyl; or c) a divalent radical selected from -(CH ₂ ) ₄ - or -(CH ₂ ) ₅ -, which is attached to R ¹ to form a fused or spirofused ring system, and is optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C ₁ -C ₆ )alkyI, halo(C ₁ -C6)alkyl, (C ₁ -C ₆ )alkoxy and oxo;

R ¹ is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-l ,3-dioxole, or (C ₃ -C ₇ )cycloalkyl ring optionally substituted with up to four substituents independently selected from the group consisting of fluorine, chlorine, bromine, cyano, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ - C ₇ )cycloalkylalkoxy, halo(C ₁ -C6)alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ -C ₆ )aIkylthio, (C ₁ - C ₆ )alkanesulfιnyl, halo(C ₁ -C ₆ )alkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, halo(C ₁ -

C ₆ )alkanesulfonyl, H ₂ NSO ₂ , H ₂ NCO, (C ₁ -C ₃ )alkylaminosulfonyi, and (C ₁ - C ₃ )alkylaminocarbonyl;

R ² is a) -H; or b) (C ₁ -C ₁₀ )alkyl, (C ₂ -C ₁₀ )alkenyl, (C ₂ -C _l0 )alkynyl, (C ₁ -C ₁₀ )alkoxy, (C ₁ -Cιo)alkylthio, (C ₁ - C ₁₀ )alkylamino, (C ₁ -C ₅ )alkoxy(C ₁ -Cj)alkyl, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )aIkylamino(C ₁ -C ₅ )alkyI, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )aIkoxy(C ₁ -C ₃ )alkylthio, (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C _l -C ₅ )alkoxy, (C ₁ -C ₅ )alkylthio(C ₁ - C^alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -

C ₅ )alkyIamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkyIamino(C ₁ -C ₅ )alkylamino _J (C ₁ -C ₃ )alkoxy(C ₁ - C ₃ )alkoxy(C ₁ -C ₃ )alkyl, aminocarbonylamino(C ₁ -C ₁₀ )alkyl, aminocarbonylamino(C ₁ - C ₁₀ )alkoxy, aminocarbonylamino(C ₁ -Cιo)alkylthio, aminocarbonyIamino(C ₁ - C ₁₀ )alkylamino, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₃ )alkanoylamino(C ₁ -C ₅ )alkylamino, aminosulfonylamino(C ₁ -C ₁₀ )aIkyl, aminosulfonylamino(C ₁ -C ₁₀ )alkoxy, aminosulfonylaminoCC ₁ -C ₁₀ ialkylthio, aminosulfonylamino(C ₁ -Cιo)alkylarnino, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₃ )alkoxy, (C ₁ - C ₅ )alkanesuIfonylamino(C ₁ -C ₃ )alkyhhio, (C ₁ -C ₅ )alkanesulfonyIamino(C ₁ -C ₅ )alkylamino, formylamino(C ₁ -C ₅ )alkyl, formyIamino(C ₁ -C ₅ )alkoxy, formylamino^j-C ₅ )alkylthio, formylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkyl, (C[- C ₃ )alkoxycarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₃ )alkylthio, (C ₁ - C ₅ )aIkoxycarbonylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkyl,

(C ₁ -C ₅ )alkyIaminocarbonyIamino(C ₁ -C ₅ )alkoxy _: , (C ₁ -C ₅ )alkylaminocarbonyIamino(C ₁ - C ₅ )alkylthio, (C ₁ -C ₅ )alkyiaminocarbonylamino(C ₁ -C ₅ )alkylamino, aminocarbonyl(C ₁ - C ₅ )alkyl, aminocarbonyl(C ₁ -C ₅ )alkoxy, aminocarbonyl(C ₁ -C ₅ )alkylthio, aminocarbonyl(C ₁ -C ₃ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonyI(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkylaminocarbonyI(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ -C,)alkylthio, (C ₁ -

C ₅ )alkyIaminocarbonyl(C ₁ -C ₅ )alkyamino, aminocarboxy(C ₁ -C ₅ )aIkyl, aminocarboxy(C ₁ - C ₅ )alkoxy, aminocarboxy(C ₁ -C ₃ )alkylthio, aminocarboxy(C ₁ -C ₅ )alkyIamino, (Q - C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )aIkylaminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkyIthio, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkylamino, (C ₁ - C ₁₀ )alkoxycarbonylamino, (C ₁ -CnOalkylarninocarbonylamino, or (C ₁ -C ₁₀ )alkanoylamino, each optionally substituted by

1) 1 to 5 fluorine atoms; and/or

2) 1 group selected from cyano, hydroxyl, (C _t -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -C])cyc)oalkyl, (C ₃ -C ₄ )cycl oalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₄ )cycloalkyl, and halo(C ₃ -C ₄ )cycloalkoxy; wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone;

R ³ is -H, halogen, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, hydroxyl, hydroxy(C ₁ -C ₃ )alkyl, hydroxy(C ₁ -

C ₃ )alkoxy, (CpC^alkanoylamino, (C ₁ -C ₃ )alkoxycarbonylamino, (C ₁ - C ₃ )alkylaminocarbonylamino, di(C ₁ -C ₃ )alkylaminocarbonylamino, (Cp

C ₃ )alkanesulfonylamino, (C ₁ -C ₃ )alkylaminosulfonylamino, di(C ₁ - C ₃ )alkylaminosulfonylamino, or phenylamino or heteroarylamino in which each phenylamino and heteroarylamino group is optionally substituted with 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, cyano, (C ₁ - C ₃ )alkyl, haIo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkanesulfonyl, and

(C ₁ -C ₃ )alkoxycarbonyl; provided that i) R ² and R ³ are not both hydrogen and ii) when R' ¹ |s hydroxyl, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ -C ₁₀ )alkoxy, (C ₁ -C _| o)alkylthio, (C ₁ -C ₁₀ )alkylamino,

(C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ - C ₅ )alkylthio, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkylamino, (C ₁ -Cj)alkylthio(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylthio, (C ₁ - C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylamino(C ₁ -C ₃ )alkylthio, (C ₁ - C ₃ )alkyIamino(C ₁ -C ₅ )alkyIamino, aminocai:bonylamino(C _| -C ₁₀ )aIkoxy, aminocarbonylamino(C _| -C ₁₀ )aIkylthio, aminocarbonyl-amino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkylthio, (C ₁ - C ₅ )aIkanoylamino(C ₁ -C ₅ )alkylamino, aminosulfonylamino(C ₁ -C ₁₀ )alkoxy,

aminosulfonylaminoCC ₁ -C ₁₀ ialkylthio, aminosulfonylamino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )-alkanesu]fonylamino(C ₁ -C ₅ )a ^] koxy, (C ₁ -C ₅ )aIkanesulfonyIamino(C ₁ - C ₅ )alkylthio, (C ₁ -C ₅ )alkanesulfonylamino^i-C^alkylamino, formylamino(C ₁ - C ₅ )alkoxy, formyIamino(C ₁ -C ₃ )alkylthio, formylamino(C ₁ -C ₅ )alkylamino, (C ₁ - C ₅ )aIkoxycarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -

C ₅ )alkylthio, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkylamino _s (C ₁ - C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )aIkoxy, (C ₁ -C ₅ )alkylaniinocarbonylamino(C ₁ - C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkylamino, aminocarbonyl(C ₁ -C ₅ )aIkoxy, aminocarbonyl(C ₁ -C ₅ )alkylthio, aminocarbonyI(C ₁ - C ₅ )alkylamino, (C ₁ -C ₅ )alkyIaminocarbonyl-(C ₁ -C ₅ )alkoxy, (C ₁ -

C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ - C ₅ )alkyamino, aminocarboxy(C ₁ -C ₃ )alkoxy, aminocarboxy(C ₁ -C ₅ )alkylthio, aminocarboxy(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ - Cj)alkyIaminocarboxy(C ₁ -C ₅ )alkylthio, (C ₁ -Ci)alkylaminocarboxy(C ₁ - Cj)alkylamino, (C ₁ -C ₁₀ )alkoxycarbonylamino, (C ₁ -C ₁₀ )alkylaminocarbonylamino, or (C ₁ -C ₁₀ )alkanoylamino, each optionally substituted with

1) 1 to 5 fluorine atoms; and/or

2) 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ - C ₃ )alkoxy, (C ₃ -C ₄ )cycloalkyl _s (C ₃ -C ₄ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₄ )cyc)oalkyl, and halo(C ₃ -C ₄ )cycloalkoxy; wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone;

Q is a divalent radical selected from the group consisting of Q1 , Q2, Q3, Q4, Q5, Q6, and Q7;

W is a bond or an unsubstituted (C ₁ -Cg)alkylene;

E is a saturated 3-, 4-, 5-, 6-, or 7-membered ring or an unsaturated 5- or 6-membered ring composed of carbon atoms and 0-3 hetero atoms selected from 0, 1 , 2, or 3 nitrogen atoms, 0

or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring atoms being substituted with the appropriate number of hydrogen atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; and

G is is hydrogen, hydroxy, (C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl-OH, -(C ₁ -C ₄ )alkyl-NR ⁴ R ^4a , -O(C ₁ -

C ₆ )alky 1-NR ⁴³ R ⁴ , -Cf=O)(C _r C ₄ )alkyl-NR ⁴ R ^4a , -C(=O)(C ₁ -C ₄ )alkylaryl, amino, amino(C ₁ - C ₆ )alkyl, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl,

-(C ₁ -C ₄ )aIkyl(C ₃ -C ₇ )cycloalkyl, or -(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocycIyl, wherein the (C ₁ -C ₄ )alkyl moiety of said -C(=O)(C ₁ -C ₄ )alkylaryl,

-C(=0)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, -(C ₁ -G,)alkyl(C ₃ -C ₇ )cycIoalkyl and -(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino, where R ⁴ is H or (C ₁ -C ₃ )alkyl and R ^4a is selected from H, (C ₁ -C ₃ )alkyl, heterocyclyl(C ₁ -C ₆ )alkyl, and (C ₄ -C ₇ )heterocyclyI(C ₁ -C ₆ )alkyl, or R ⁴ and R ^4a , taken together with the nitrogen atom to which they are attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1-3 heteroatoms selected from 1 , 2, or 3 nitrogen atoms and 0 or 1 oxygen atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, amino, (C ₁ -C ₆ )alkyl,

(C ₁ -C _< s)alkylamino, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyI, amino(C ₁ -C ₆ )alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, or an enantiomer, diastereomer, or salt thereof.

17. The compound of any one of Claims 4 to 15, wherein:

R is: a) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₃ -C ₇ )cycloalkenyl, (C ₃ - C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkylethenyl, (C ₃ -C ₇ )cycloalkylethynyl, (C ₁ - C ₈ )alkoxy, (C ₃ -C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -

C ₃ )alkoxy, piperidino, pyrrolidino or tri(Cs-C ₃ )alkylstlyl, each optionally substituted with up to 4 substituents independently selected from the group consisting of fluorine, hydroxy, (C ₁ -C ₃ )alkyl, and haIo(C ₁ -C ₃ )alkyl, b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C ₁ - C ₃ )alkoxy, or monocyclic heteroaryl(Cι -C ₃ JaIkOXy, each optionally substituted with up to three substituents independently selected from the group consisting of halogen, cyano, (C ₁ - C ₃ )alkyl, (C ₃ -C ₃ )cycloalkyl, halo(C ₁ -C ₃ )alkyI, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ - C ₃ )alkylthio, and H ₂ NCO; or

c) a divalent radical selected from -(CH ₂ ) ₄ - or -(CH ₂ ) ₅ -, which is attached to R ¹ to form a fused or spirofused ring system;

R ¹ is phenyl, monocyclic heteroaryl ring, bicyclic heteroaryl ring or benzo-1 ,3-dioxole, optionally substituted with up to four substituents independently selected from the group consisting of halogen, cyano, (C ₁ -C ₃ )alkyl, (C ₃ -C ₄ )cycloalkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )aIkoxy, and H ₂ NCO;

R ² is -H, (C ₁ -C ₈ )alkyl, (C ₄ -C ₉ )cycloalkylalkyl, fluoro(C ₁ -C ₈ )aIkyl, fluoro(C ₄ -C ₉ )- cycloalkylalkyl, (C ₁ -C ₈ )alkoxy, (C ₄ -C ₉ )cycloalkylalkoxy, fluoro(C ₁ -C ₈ )alkoxy, hydroxy(C ₁ -C ₈ )alkyl, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkyl, halo(C ₁ -Cj)alkylamino(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )hydroxyalkyl, (C ₁ -C ₄ )cycloalkoxy(C ₁ -C ₃ )alkyl, ftuoro(C ₁ -C ₃ )alkoxy(C ₁ - C ₅ )alkyl, fluoro(C ₃ -C ₄ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )aIkoxy(C ₁ -C ₅ )alkc>xy, hydroxy(C ₁ -C ₈ )alkoxy, (C ₃ -C ₄ )cycloaIkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -C ₃ )alkoxy(C ₁ -Cj)alkoxy, fluoro(C ₃ -C ₄ )cycloalkoxy(C ₁ -C ₅ )alkoxy, (C ₁ -

C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )aIkyl, fIuoro(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkyl, aminocarbonylamino(C ₁ -Cs)alkyl, aminocarbonylamino(C ₁ -C ₈ )alkoxy, (C ₁ - C ₅ )aIkanoylamino(C ₁ -C ₅ )alkyI, (C ₁ -C ₅ )alkanoylaminoCC ₁ -C ₅ )alkoxy, fluoro(C ₁ - C ₅ )alkanoylamino(C ₁ -C ₅ )alkyl, fluoro(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₃ )alkoxy(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkanoylamino(C ₁ -

C ₅ )alkoxy, (C ₃ -C ₄ )-cyc]oalkanecarbonyllamino(C ₁ -C ₅ )alkyl, (C ₃ - C ₄ )cycloalkanecarbonyllamino(C ₁ -C ₅ )aIkoxy, aminosulfonylamino(C ₁ -C ₈ )alkyl, aminosulfonylamino(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkane-su]fonylamino(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₅ )aIkoxy, formylamino(C ₁ -C ₅ )aIkyl, formylamino(C ₁ - C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxycarbonyl-amino(C ₁ -

C ₅ )alkoxy, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylamino- ' carbonylamino(C ₁ -C ₅ )alkyl, di(C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, aminocarbonyl(C ₁ -C ₅ )alkyl, aminocarbonyl(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkyIaminocarbonyl(C ₁ - C ₅ )alkyl, (C ₁ -C ₅ )alkylaminocarbonyl(C _| -C ₅ )alkoxy, aminocarboxy(C ₁ -C ₅ )alkyl, aminocarboxy(C ₁ -C ₅ )aIkoxy, (C ₁ -Cj)alkylaminocarboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylamino- carboxy(C ₁ -Cj)alkoxy, (C ₁ -C ₈ )alkoxycarbonyIamino, (C ₁ -C ₈ )alkylaminocarbonylamino, (C ₁ -C ₈ )alkanoyIamino, fluoro(C ₁ -C ₈ )alkoxycarbonylamino, fluoro(C ₁ - C _a )alkylaminocarbonylamino, or fluoro(C ₁ -C ₈ )alkanoylamino;

R ³ is -H, halogen, OH, (C ₁ -C ₄ )alkanoylamino, or (C ₁ -C ₃ )alkoxy; provided that i) R ² and R ³ are not both hydrogen; and

ii) when R ³ is OH or halogen, R ² is not (C ₁ -C ₈ )alkoxy, (C ₄ -C ₈ )cycloalkylalkoxy, fluoro(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, hydroxy(C ₁ -C ₈ )alkoxy, (C ₃ - C ₄ )cycloaIkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -C ₅ )aIkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₃ - C ₄ )cycloalkoxy(C ₁ -C ₅ )alkoxy, aminocarbonylamino(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )- alkanoylamino(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -

C ₃ )aIkoxy(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₃ -C _< ι)cycloalkanecarbonyllamino(C ₁ - C ₅ )alkoxy, aminosulfonylamino(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -Cj)alkoxy, formylamino(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkoxy, di(C ₁ - C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, aminocarbonyI(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy, aminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₈ )alkoxy-carbonylamino, (C ₁ - C ₈ )alkylaminocarbonylamino, (C ₁ -C ₈ )alkanoylamino, fluoro(C ₁ -C ₈ )alkoxy-carbonylamino, fluoro(C ₁ -C ₈ )alkyIaminocarbonylamino, or fluoro(C ₁ -C ₈ )alkanoylamino;

Ring A is piperidine, morpholine or benzene;

Q is Q1 , Q2, Q4, or Q6;

W is a bond or an unsubstituted (C ₁ -C ₃ )alkylene;

E is a saturated 3-, 4-, 5-, or 6-membered ring or an unsaturated 5- or 6-mcmbered ring, wherein said ring is composed of carbon atoms, and 0-3 hetero atoms selected from 0, 1 , 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally substituted with up to four groups independently selected from fluorine, hydroxy, (C ₁ - C ₃ )alkyl, hydroxy(C ₁ -C ₃ )alkyI, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; and

G is hydrogen, (C ₄ -C ₇ )heterocyclyl, -O(C ₁ -C ₆ )alkyl-NR ^4a R ⁴ , amino, amino(C ₁ -C ₃ )alkyl, (C ₁ - C ₃ )alkylamino(C ₁ -C ₃ )alkyI,-(C ₁ -C ₃ )alkyl-OH, -(C ₁ -C ₃ )alkyl-NR''R ^4a ,

-C(=O)(C ₁ -C ₃ )alkyl-NR ⁴ R ^4a , -C(=O)(C ₁ -C ₃ )alkylphenyI, -C(=0)(C ₁ -C ₃ )alkyl(C ₄₁ -C ₆ )heterocyclyl, -(C ₁ -C ₃ )alkyl(C ₃ -C ₆ )cycloalkyl, or -(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl, wherein the (C ₁ -C ₃ )alkyl moiety of said -C(=O)(C ₁ -C ₃ )alkylphenyl, -C(==O)(C ₁ -C ₃ )alkyl(C ₄ -C6)heterocyclyl, -(C ₁ -C ₃ )alkyl(C ₃ -C _fi )cycloalkyI and -(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkyIamino, where R ⁴ is H or (C ₁ -C ₃ )alkyl and R ^4a is selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₃ )cycloalkyl(C ₁ -C ₃ )alkyl ₍ and (C ₄ -C ₆ )heterocycIyI(C ₁ -C ₃ )alkyl;-

or an enantiomer, diastereomer, or salt thereof.

18. The compound of any one of Claims 4 to 15, wherein R is: a) (C ₁ -C ₇ )alkyl, (C ₃ -C ₇ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyt, (C ₁ -C ₇ )alkoxy, (C ₃ -C ₇ )cycloalkoxy,

(C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )aIkoxy, piperidino, pyrrolidine or tri(C ₁ -C ₃ )alkylsilyl, each optionally substituted with up to 4 substituents independently selected from fluorine, hydroxy, (C ₁ -C ₃ )alkyl, or halo(C ₁ -C ₃ )alkyl; or b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C ₁ - C ₃ )alkoxy, or monocyclic heteroaryI(C ₁ -C ₃ )alkoxy, each optionally substituted with up to 3 substituents independently selected from fluorine, chlorine, cyano, (C ₁ -C ₃ )alkyl, (C ₃ - C ₄ )cycloalkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkylthio or H ₂ NCO; or c) -(CH ₂ ),- or -(CH ₂ ) _S -;

R ¹ is phenyl, furan, thiophene, pyrrole, pyrazole," imidazole, oxazole, thiazole, pyridine, pyrimidine, pyrazine, benzofuran, benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, quinazoline or benzo-l ,3-dioxole, each optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C ₁ -C ₃ )alkyI, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, and carboxamide; R ² is (C ₁ -C ₃ )aIkoxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₃ -C ₄ )cycloalkyl(C ₁ -Q)alkyl, (C ₃ -C ₄ )cycloalkyl(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkoxycarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )- alkoxycarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )- alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkylaminocarbonyI(C ₁ -C ₅ )alkyl or (C ₁ - C ₃ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy;

R ³ is hydrogen, fluoro, hydroxyl, or (C ₁ -C ₄ )alkanoylamino, provided that when R ³ is hydroxyl or fluoro, R ² is not (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₃ -G,)cycloalkyl(C ₁ -C ₅ )alkoxy, (C ₁ - C ₃ )alkoxy-carbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkanoylamino(C ₁ -C ₅ )alkoxy or (C _\ - C ₃ )alkylaminocarbonyI(C ₁ -C ₅ )alkoxy;

Ring A is piperidine, morpholine, or benzene;

Q is Q1, Q2, Q4 or Q6;

W is a bond or an unsubstituted (C ₁ -C ₂ )alkylene

E is a saturated 3-, 4-, 5-, or 6-membered ring or an unsaturated 5- or 6-membered ring composed of carbon atoms and 0 or 1 nitrogen atoms, said ring being optionally substituted

with up to one hydroxy or hydroxy (C ₁ -C ₃ )alkyl group and with up to two (C ₁ -C ₃ ) alkyl groups; and

G is hydrogen, (C ₅ -C ₆ )heterocyc]yl, -O(C ₁ -C ₆ )alkyl-NR ^4a R ⁴ , amino, (C ₁ -C ₂ )alkylamino, amino(C ₁ -C ₂ )alkyl, (C ₁ -C ₂ )aIkylamJno(C ₁ -C ₂ )alkyl,-(C ₁ -C ₂ )alkyl-OH,

-C(=O)(C ₁ -C ₂ )alkyl-NR ⁴ R ^4a , or -C(=O)(C ₁ -C ₂ )alkylphenyl, wherein the (C ₁ -C ₂ )alkyl moiety of said -C(=O)(C ₁ -C ₂ )alkylphenyl is substituted by amino or (C ₁ -C ₂ )alkylamino, where R ⁴ is H or (C ₁ -C ₂ )alkyl and R ^4a is H.

19. The compound of any one of Claims 4 to 15, wherein

R is ethyl, isobutyl, t-butyl, 2,2-dimethyI-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2- (cyclopropyl)ethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropyIphenyl, 3- cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-

(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyI, 4-methylphenyl, 2,3- difluorophenyl, 2-fIuoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 5-methyI-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophenoxy, 2-chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3- fluorophenoxy, 3-methylphenoxy, 4-fluorophenoxy, 4-methylphenoxy, 2-methyl-4- fluorophenoxy, 2-methyl-5-fluorophenoxy, piperidino, trimethylsilyl, -(CH ₂ ),,- or -(CH ₂ )s-;

R ¹ is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl,

4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, ' benzofuran, benzothiophene, benzooxazole or benzo-l ,3-dioxole;

R ² is 4-methoxybutyl, 4-ethoxybutyl, 4-methoxypentyl, 3-methoxypropoxy, 3-

(methoxycarbonylamino)propyl, 3-(acetylamino)propyl, 2-(acetylamino)ethoxy, or 2- (methoxycarbony lam ino)ethoxy ;

R ³ is hydrogen or hydroxyl provided that when R ³ is hydroxyl, R ² is not 3-methoxypropoxy, 2- (acetylamino)ethoxy, or 2-( methoxycarbonylamino)ethoxy;

Ring A is piperidine, morpholine, or benzene;

Q is Q1, Q4, or Q6;

W is a bond or an unsubstituted (C _t )alkylene;

E is azetidine, pyrrolidine, hydroxypyrrolidine, (hydroxymethyl)pyrrolidine, methylpyrrolidine, piperidine, hydroxypiperidine, cyclopropane, methylcyclopropane, cyclopentane, hydroxycyclopentane, cyclohexane, hydroxycyclohexane, or pyridine; and

G is -H, -OH, -CH ₂ OH, -NH ₂ , -NHCH ₃ , -CH ₂ NH ₂ , -CH ₂ NHCH ₃ , -CH ₃ , -CH ₂ CH ₂ OH,

-CH ₂ CH ₂ NH ₂ , -CH ₂ NHCH ₂ CH ₃ , -CH ₂ NHCH(CH ₃ ) ₂ , -CH ₂ N(CH ₃ ) ₂ , -OCH ₂ CH ₂ NH ₂ , -C(=O)CH ₂ NH ₂ , -CH ₂ NHCH ₂ (C ₆ H _n X or (R)-C(=O)CH(N H ₂ )CH ₂ (C ₆ H ₅ ).

20. A pharmaceutical composition comprising a compound of any one of Claims 1-19, or an enantiomer, diastereomer, or salt thereof and a pharmaceutically acceptable carrier or excipient.

21. The pharmaceutical composition of Claim 20, further comprising an additional agent selected from the group consisting of α-blockers, β ₇ blockers, calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, dual ACE and neutral endopeptidase (NEP) inhibitors, angiotensin-receptor blockers (ARBs), aldosterone synthase inhibitors, aldosterone-receptor antagonists, and endothelin receptor antagonists.

22. A method of antagonizing aspartic protease inhibitors in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of any one of Claims 1-19 or an enantiomer, diastereomer, or salt thereof.

23. The method of Claim 22,wherein the aspartic protease is renin.

24. A method for treating or ameliorating an aspartic protease mediated disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound of any one of Claims 1 -19, or an enantiomer, diastereomer, or salt thereof.

25. The method of Claim 24 wherein the aspartic protease is β-secretase.

26. The method of Claim 24, wherein the aspartic protease is plasmepsin.

27. The method of Claim 24, wherein the aspartic protease is HIV protease.

28. A method for treating or ameliorating a renin mediated disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound of any one of Claims 1 -19, or an enantiomer, diastereomer, or salt thereof.

29. The method of Claim 28, wherein the renin mediated disorder is hypertension, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy post-infarction, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, post-surgical hypertension, restenosis following angioplasty, raised intra-ocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, anxiety states, or a cognitive disorder.

30. A method for the treatment of hypertension in a subject in need thereof comprising administering to the subject a compound of any one of Claims 1-19 in combination therapy with one or more additional agents said additional agent selected from the group consisting of α-blockers, β-blockers, calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, dual ACE and neutral endopeptidase (NEP) inhibitors, angiotensin-receptor blockers (ARBs), aldosterone synthase inhibitors, aldosterone-receptor antagonists, and endothelin receptor antagonists.

31. The method of Claim 30, wherein: the α-blockers are selected from the group consisting of doxazosin, prazosin, tamsulosin, and terazosin; the β-blockers are selected from the group consisting of atenolol, bisoprol, metoprolol, acetutolol, esmolol, celiprolol, taliprolol, acebutolol, oxprenolol, pindolol, propanolol, bupranolol, penbutolol, mepindolol, carteolol, nadolol, and carvedilol, or pharmaceutically acceptable salts thereof; the calcium channel blockers are selected from the group consisting of dihydropyridines (DHPs) and non-DHPs, wherein the DHPs are selected from the group consisting of amlodipine, felodipine, ryosidine, isradipine, lacidipine, nicardipine, nifedipine, nigulpidine, modiphine, nisoldipine, nitrendipine, and nivaldipine and their pharmaceutically acceptable salts and the non- DHPs are selected from the group consisting of flunarizine, prenylamine, diltiazem, fendiline, gallopamil, mibefradil, anipamil, tiapamil, and verampimil, or pharmaceutically acceptable salts thereof; the diuretics is a thiazide derivative selected from the group consisting of an amiloride, chlorothiazide, hydrochlorothiazide, methylchlorothiazide, and chlorothalidon; the ACE inhibitors are selected from the group consisting of alacepril, benazepril, benazaprilat, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, lisinopril, moexipiril, moveltopril, perindopril, quinapril, quinaprilat, ramipril, ramiprilat, spirapril, temocapril, trandolapril, and zofenopril; dual ACE/NEP are selected from the group consisting of include omapatrilat, fasidotril, and fasidotrilat;

the ARBs are selected from the group consisting of candesartan, eprosartan, irbesartan, losartan, oimesartan, tasosartan, telmisartan, and valsartan; the aldosterone synthase inhibitors are selected from the group consisting of anastrozole, fadrozole, and exemestane; the aldosterone-receptor antagonists are selected from the group consisting of spironolactone and eplerenone; and the endothelin antagonists are selected from the group consisting of bosentan, enrasentan, atrasentan, darusentan, sitaxentan, and tezosentan, or pharmaceutically acceptable salts thereof.

32. The method of Claim 31.wherein the compound and the additional agents are administered by sequential administration or simultaneous administration.

ABSTRACT OF THE DISCLOSURE

Disclosed are compounds according to Formula 1:

wherein the variables are defined herein. Such compounds are can bind aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity.

Also described herein are methods of antagonizing aspartic protease inhibitors in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound according to Formula I.

- 1 - RENIN INHIBITORS

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 60/789,703, filed April 5, 2006 and U.S. Provisional Application No. 60/789,823, filed April 5, 2006, the entire teachings of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Aspartic proteases, including renin, β-secretase (BACE), Candida albicans secreted aspartyl proteases, HIV protease, HTLV protease and plasmepsins I and II, are implicated in a number of disease states. In hypertension elevated levels of angiotensin I ₁ the product of renin catalyzed cleavage of angioteninogen are present. Elevated levels of β-amyloid, the product of BACE activity on amyloid precursor protein, are widely believed to be responsible for the amyloid plaques present In the brains of Alzheimer's disease patients. Secreted aspartyl proteases play a role in the virulence of the pathogen Candida albicans. The viruses HIV and HTLV depend on their respective aspartic proteases for viral maturation. Plasmodium falciparum uses plasmepsins I and II to degrade hemoglobin.

In the renin-angiotensin-aldosterone system (RAAS) the biologically active peptide angiotensin II (Ang II) is generated by a two-step mechanism. The highly specific aspartic protease renin cleaves angiotensinogen to angiotensin I (Ang I), which is then further processed to Ang II by the less specific angiotensin-converting enzyme (ACE). Ang II is known to work on at least two receptor subtypes called ATi and AT ₂ . Whereas AT _t seems to transmit most of the known functions of Ang II, the role OfAT ₂ is still unknown.

Modulation of the RAAS represents a major advance in the treatment of cardiovascular diseases (Zaman, M. A. et al Nature Reviews Drug Discovery 2002, /, 621-636). ACE inhibitors and ATi blockers have been accepted as treatments of hypertension (Waeber B. et al., "The renin- angiotensin system: role in experimental and human hypertension", in Berkenhager W. H., Reid J. L. (eds): Hypertension, Amsterdam, Elsevier Science Publishing Co, 1996, 489-519; Weber M. A., Am. J. Hypertens., 1992, 5, 247S). In addition, ACE inhibitors are used for renal protection (Rosenberg M. E. et al., Kidney International, 1994, 45, 403; Breyer J. A. et al., Kidney International, 1994, 45, S156), in the prevention of congestive heart failure (Vaughan D. E. et al, Cardiovasc. Res., 1994, 28, 159; Fouad-Tarazi F. et al., Am. J. Med., 1988, 84 (Suppl. 3A), 83) and myocardial infarction (Pfeffer M. A. et al, N Engl. J: Med, 1992, 327, 669).

Interest in the development of renin inhibitors stems from the specificity of renin (Kleinert H. D., Cardiovasc. Drugs, 1995, 9, 645). The only substrate known for renin is angiotensinogen, which can only be processed (under physiological conditions) by renin. In contrast, ACE can also cleave bradykinin besides Ang 1 and can be bypassed by chymase, a serine protease (Husain A., J. Hypertens., 1993, / /, 1 155). In patients, inhibition of ACE thus leads to bradykinin accumulation causing cough (5-20%) and potentially life-threatening angioneurotic edema (0.1-0.2%) (Israili Z. H. et al., Annals of Internal Medicine, 1992, 117, 234). Chymase is not inhibited by ACE inhibitors.

- 2 -

Therefore, the formation of Ang II is still possible in patients treated with ACE inhibitors. Blockade of the ATI receptor (e.g., by losartan) on the other hand overexposes other AT-receptor subtypes to Ang II, whose concentration is dramatically increased by the blockade of ATI receptors. In summary, renin inhibitors are not only expected to be superior to ACE inhibitors and AT| blockers with regard to safety, but more importantly also with regard to their efficacy in blocking the RAAS. Only limited clinical experience (Azizi M. et ai, J, Hypertens., 1994, 12, 419; Ncutcl J. M. et a/., Am. Heart, 1991, 122, 1094) has been generated with renin inhibitors because their peptidomimetic character imparts insufficient oral activity (Kleinert H. D., Cardiovasc. Drugs, 1995, 9, 645). The clinical development of several compounds has been stopped because of this problem together with the high cost of goods. It appears as though only one compound has entered clinical trials (Rahuel J. et a/., Chem. Biol., 2000, 7, 493; Mealy N. E., Drugs of the Future, 2001, 26, 1 139). Thus, metabolically stable, orally bioavailable and sufficiently soluble renin inhibitors that can be prepared on a large scale are not available. Recently, the first non-peptide renin inhibitors were described which show high in vitro activity (Oefner C. et ai, Chem. Biol., 1999, 6, 127; Patent Application WO 97/0931 1 ; Maerki H. P. et al, Il Farmaco, 2001,5(5,21). The present invention relates to the unexpected identification of renin inhibitors of a non-peptidic nature and of low molecular weight. Orally active renin inhibitors which are active in indications beyond blood pressure regulation where the tissular renin-chymase system may be activated leading to pathophysiological^ altered local functions such as renal, cardiac and vascular remodeling, atherosclerosis, and restenosis, are described.

All documents cited herein are incorporated by reference.

SUMMARY OF THE INVENTION Compounds have now been found which are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity.

One embodiment the present invention is directed to compounds represented by Formula I:

wherein R is: a) hydrogen; b) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, (C ₃ -C ₁ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₂ -C ₃ )alkenyl, (C ₃ -C ₇ )cycloalkyl(C ₂ - QOalkynyl, (C ₁ -C ₃ )alkoxy, (C ₃ -C ₈ )alkenyloxy, (C ₃ -C ₈ )alkynyloxy, (C ₃ -C ₇ )cycloalkoxy, (C ₅ -C ₇ )cycloalkenyloxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )aIkoxy,

(C ₅ -C ₇ )cycloalkenyl(C ₁ -C ₃ )alkoxy, (C ₁ -C ₈ )alkylthio, (C ₃ -C ₈ )alkenylthio, (C ₃ - C ₈ )alkynylthio, (C ₃ -C ₇ )cycloalkylthio(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloaIkyl(C ₁ -C ₃ )alkyithio, (C ₅ -

- 3 -

C ₇ )cycIoalkenyl(C ₁ -C ₃ )alkylthio, (C ₁ -C ₈ )alkylamino, di(C ₁ -C ₈ )alkylamino, azepano, azetidino, piperidino, pyrrolidine (C ₃ -C ₇ )cycloalkylamino, ((C ₃ -C ₇ )cycloalkyl(C ₁ - C ₃ )alkyl)amino, or tri(C ₁ -C ₄ )alkylsilyl, each optionally and independently substituted with zero to four substituents selected from the group consisting of halogen, hydroxy, (C ₁ - C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )cycloalkoxy and oxo; c) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, aryl(C ₁ -C ₃ )alkoxy, heteroaryl(C ₁ -C ₃ )alkoxy, aryl(C ₂ -C ₃ ))alkenyl, aryl(C ₂ -C ₃ )alkynyl, heteroaryl(C ₂ -C ₃ )alkenyl, or heteroaryl(C ₂ -C ₃ )alkynyl, each optionally and independently substituted with zero to three substituents selected from the group consisting of: halogen, cyano, nitro, amino, hydroxy, carboxy; (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -

C ₇ )cyctoalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )-cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C,-C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycloalkoxy, halo(C ₄ - C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkyIthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkythio, halo(C ₄ -C ₇ )cycloalkyIalkylthio, (C ₁ -

C ₆ )alkanesulfinyl, (C ₃ -C ₆ )cycloalkanesulfϊnyl, (C ₄ -C ₇ )cycloalkylalkanesuirinyl, halo(C ₁ - C ₆ )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (G,-C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, halo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ -C ₇ )cyclo- alkylalkanesulfonyl, di(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(Cp

C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, H ₂ NCO, H ₂ NSO ₂ , (C ₁ -C ₆ )alkylaminocarbonyl, and di(C ₁ -C6)alkylaminocarbonyl, (C ₁ -C ₆ )alkylaminosulfonyl, and di(C ₁ -C ₆ )alkylaminosulfonyl; or d) a divalent radical selected from -(CH ₂ ) ₃ -, -(CH ₂ V, -(CH ₂ )s- or -(CH ₂ ) ₆ -, which is attached to R ¹ to form a fused or spirofused ring system, and is optionally and independently substituted with zero to four substituents selected from: halogen, hydroxy, halo(C ₁ - C ₆ )alkyl, (C ₁ -C ₆ )alkoxy and oxo;

R ¹ is phenyl, monocyclic heteroaryl, bJcyclic heteroaryl, benzo-l ,3-dioxole, benzo-l,3-dioxine, 2,3-dihydrobenzo-l ,4-dioxine or (C ₃ -C ₇ )cycloalkyl, each optionally and independently substituted with zero to four substituents selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ - C ₆ )alkynyl, (C ₃ -C ₆ )-cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, ha!o(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycIoalkoxy, halo(C ₄ t-C ₇ )cycloalkylaIkoxy, (C ₁ -

C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ -C ₇ )cycloalkylalkylthio, haIo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkythio, halo(C ₄ -C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ - C ₆ )cycloalkanesulfιnyl, (C ₄ -C ₇ )cycloalkylalkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyl,

- 4 -

halo(C ₃ -C ₆ )cycIoaIkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyI, (C ₁ - C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfbnyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ - C ₆ )alkanesulfbnyl, halo(C ₃ -C ₆ )cycloaIkanesulfonyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₅ )alkoxy, halo(C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, H ₂ NSO ₂ , H ₂ NCO, (C ₁ -

C ₆ )alkylaminosulfonyl, di(C ₁ -C ₆ )alkylaniinosulfonyl, (C ₁ -C ₆ )alkylaminocarbonyl and di(C ₁ -C ₆ )alkylaminocarbonyl;

X and Y are each independently CH ₂ or a single bond;

R ² is: a) -H; or b) (C ₁ -C _I2 )alkyI, (C ₂ -C ₁₂ )alkenyl, (C ₂ -C , ₂ )alkynyl, (C ₁ -C _]2 )alkoxy, (C ₁ -C _l2 )alkylthio, (C ₁ - C ₁₂ )alkylamino, oxo(C ₁ -C ₁₂ )alkyI, oxo(C ₂ -C ₁₂ )alkenyl, oxo(C ₂ -C ₁₂ )alkynyl, oxo(C ₁ - C ₁₂ )alkoxy, oxo(C ₁ -C ₁₂ )alkylthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl,

(C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )aIkyl, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkylamino, (C ₁ -C _fi )alkylthio(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )aIkylamino(C ₁ -C _fi )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkylamino, (C ₁ -C ₄ )alkoxy(C ₁ -C ₄ )alkoxy(C ₁ -C ₄ )alkyl, aminocarbonylamino(C ₁ - C ₁₂ )alkyl, aminocarbonylamino(C ₁ -C ₁₂ )alkoxy, aminocarbonylamino(C ₁ -C ₁₂ )alkylthio, aminocarbonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ -Cβ)alkanoylaminotC ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkanoylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino(C ₁ -C ₆ )aIkylthio, (C ₁ - C ₆ )alkanoylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkyI, (C ₁ - • C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ -

C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )acyIoxy(C ₁ -C ₃ )aIkyl, (C ₁ -C ₆ ) acyloxy(C ₁ - QOalkoxy, (C ₁ -Ce) acyloxy(C ₁ -C ₃ )alkylthio, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkylamino, aminosulfonylamino(C ₁ -Cn )alkyl, aminosulfonylamino(C ₁ -C ₁₂ )aIkoxy, aminosulfonylamino(C ₁ -C ₁₂ )aIkylthio, aminosulfonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkanesulfonyIamino(C ₁ -C ₃ )alkoxy, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C _fi )alkanesulfonylamino(C ₁ -C ₆ )alkylamino, formylamino(C ₁ -C ₆ )alkyl, formylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ -C ₆ )alkylthio, formylamino(C ₁ -C6)alkylamino, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkyJ,

(C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ - C6)alkylthio, (C ₁ -C6)aIkylaminocarbonylamino(C ₁ -C ₃ )alkylamino, aminocarbonyl(C _t - C ₆ )alkyl, aminocarbonyl(C ₁ -C ₆ )alkoxy, aminocarbonyl(C ₁ -C ₆ )alkylthio,

- 5 -

aminocarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkyIaminocarbonyI(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkyIaminocarbonyl(C ₁ -C ₆ )alkyamino, aminocarboxy(C ₁ -C ₆ )alkyl, aminocarboxy(C ₁ - C ₆ )alkoxy, aminocarboxy(C ₁ -C ₆ )alkylthio, aminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ - C ₆ )alkyIaminocarboxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₃ )alkylaminocarboxy(C ₁ -C ₆ )alkoxy, (C ₁ -

C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ - C ₁₂ )alkoxycarbonylamino, (C ₁ -C _{1 2} )alkylaminocarbonylamino, or (C ₁ -C ₁₂ )alkanoylamino, each optionally substituted by: 1) 1 to 5 halogen atoms; and/or 2) 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -

C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ - C ₆ )cycloalkyl, and halo(C ₃ -Ca)cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to a thiocarbonyl groups;

R ³ is hydrogen, halogen, (C ₁ -C ₆ )alkyl, (C ₁ -C ₃ )alkoxy, hydroxyl, hydroxy(C _l -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino, (C ₁ -C ₆ )alkoxycarbonylamino, (C ₁ - C ₆ )alkylaminocarbonylamino, di(C ₁ -C ₆ )alkylaminocarbonylamϊno, (C ₁ - C ₆ )alkanesulfonylamino, (C ₁ -C ₆ )alkylaminosulfonylamino, di(C ₁ -

C ₆ )alkylaminosulfonylamino, phenylamino or heteroarylamino in which each phenylamino or heteroarylamino group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ - C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )- cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -

C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -C ₆ )cycloalkoxy, halo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ - C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkylthio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkylthio, halo(C ₄ -C ₇ )cycloaIkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ - C ₆ )cycloalkanesulfinyl, (C ₄ -C ₇ )cycloalkylalkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyI, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyI, (C ₁ - C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ - C ₆ )alkanesulfonyl, halo(C ₃ -C ₆ )cycloalkanesu!fonyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkytamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, halo(C ₁ - C ₆ )aIkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, aminocarbonyl, (C ₁ -

C ₆ )alkylaminocarbonyl, and di(C ₁ -C ₃ )alkylaminocarbonyl; provided that: i) R ² and R ³ arc not both hydrogen; and

- 6 -

ii) when R ³ is hydroxy, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ -C ₁₂ )alkoxy, (C ₁ -C ₁₂ )alkylthio, (C ₁ -C ₁₂ )alkylamino, oxo(C ₁ -C i ₂ )alkoxy, oxo(C ₁ -C] ₂ )alkylthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio(C ₁ -

C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ - C _fi )alkoxy, (C ₁ -Q^alkylaminotC ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkylamino, aminocarbonylamino(C ₁ -C _l2 )alkoxy, aminocarbonylamino(C ₁ - C ₁₂ )alkylthio, aminocarbonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkanoylamino(C ₁ - C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkanoylamino(C ₁ -

C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ ) acyloxy(C ₁ - C _fi )alkoxy, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkylamino, aminosu]fonylamino(C ₁ -C ₁₂ )alkoxy, aminosulfonyIamino(C ₁ -C ₁₂ )alkylthio, aminosulfonylamino(C ₁ -C ₁₂ )alkyIamino, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -

C ₆ )alkoxy, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkanesulfonyIamino(C ₁ -C ₆ )alkylamino, formylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ -C ₆ )alkyIthio, formylamino(C ₁ -C ₆ )alkylamino, (C ₁ - C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ - C _fi )alkylthio, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylamino ₍ (C ₁ -

C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkyIaminocarbonylamino(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkylamino, aminocarbonyl(C ₁ -C ₆ )alkoxy, aminocarbonyl(C ₁ -C ₆ )alkylthio, aminocarbonyl(C ₁ - C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -

C ₆ )alkylamino, aminocarboxy(C ₁ -C ₆ )alkoxy, aminocarboxy(C ₁ -C _fi )alkylthio, aminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkyIaminocarboxy(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylaminocarboxy(C ₁ -Ca)alkylthio, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ - Cβ)alkylamino, (C ₁ -C ₁₂ )alkoxycarbonylamino, (C ₁ -C ₁₂ )alkylaminocarbonylamino, or (C ₁ -C ₁₂ )alkanoylamino, each optionally substituted by:

1) I to 5 halogen atoms; and/or

2) 1 group selected from cyano, hydroxy, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₆ )cycloalky ⁾ , or halo(C ₃ -C ₆ )cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to thiocarbonyl groups;

- 7 -

A is a saturated or unsaturated 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ ),,, via bonds to two members of said ring, wherein said ring is composed of carbon atoms and 0-2 hetero atoms selected from the group consisting of 0, 1, or 2 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally and independently substituted with zero to four halogen atoms, (C ₁ -C ₆ )alkyl groups, halo(C ₁ -C ₆ )alkyl groups or oxo groups such that when there is substitution with one oxo group on a carbon atom it • forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; and m is 1 to 3;

Q and Y are attached to carbon or nitrogen atoms in ring A in a 1 ,2-, 1 ,3-, or 1 ,4- relationship;

Q is a divalent radical selected from

wherein A and E are attached to the truncated bonds

Q7 Q8 Q9 Q10

W is a bond or an (C ₁ -C ₆ ) alkylene and

W is optionally and independently substituted by zero to four groups selected from:

1) (C ₁ -C ₁₂ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₃ -C ₈ )cycIoalkyl(C ₁ -C ₃ )alkyl, (C ₂ -C ₁₂ )alkenyl, (C ₅ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkenyl, (C ₂ -C ₁₂ )alkynyl, (C ₃ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkynyl, (C ₄ - C ₁₂ )bicycloalkyl(C ₁ -C ₃ )alkyl, (C ₈ -C ₁₄ )tricycloalkyl(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkyl, (C ₃ -

C ₈ )cycloalkylthio(C ₁ -C ₃ )alkyl, saturated heterocyclyl, saturated heterocyciyl(C ₁ -C ₃ )alkyl, hydroxy and oxo wherein:

(a) hydrogen atoms in these groups are optionally and independently substituted by zero to six groups selected from: halogen, cyano, hydroxy, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -

C ₆ )cycloalkyl, halo(C ₃ -C ₆ )cycloalkoxy and wherein

(b) divalent sulfur atoms are optionally oxidized to sulfoxide or sulfone; or

2) phenyl, naphthyl, heteroaryl, phenyI(C ₁ -C ₃ )alkyl, naphthyl(C ₁ -C ₃ )alkyl, and heteroaryl(C ₁ -C ₃ )alkyl, each optionally and independently substituted with zero to three

- 8 -

groups selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )cycloalkyl-(C ₂ - C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ - C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ - Q)cycloalkoxy, halo(C ₄ -C ₇ )cyc]oalkylalkoxy, (C ₁ -C6)alkylthio, (C ₃ -C _fi )cycloalkylthio,

(C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₅ )cycloalkylthio, halo(C ₄ - C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ -C ₆ )cycloalkanesulfinyl, (C ₄ - C ₇ )cycloalkylalkanesulFinyl, halo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfinyl, (C ₁ -Cg)alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl., halo(C ₃ -

C ₆ )cycloalkanesulfonyl, halo(C ₄ -C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ - C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ - Cή)alkoxycarbonyl, aminocarbonyl, (C ₁ -C ₆ )alkylaminocarbonyl, di(C ₁ - C ₆ )alkylaminocarbonyl, cyano(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, carboxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C ₆ )alkyl, (C ₄ -C ₃ )cycloalkylalkoxy(C ₁ -

C ₆ )alkyl, halo(C _t -C ₆ )alkoxy(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkoxy(C ₁ -C ₆ )alkyl, halo(C ₄ - C ₈ )cycloalkylalkoxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylthio(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalky HhIo(C ₁ - C ₆ )alkyl, (C ₄ -C ₈ )cycloalkylalkylthio(C ₁ -C ₆ )aIkyl, halo(C ₁ -C ₈ )alkylthio(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₈ )cycloalkylthio(C ₁ -C ₆ )alkyl _J halo(C ₄ -C ₈ )cycloalkylalkylthio(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkanesulfinyl(C ₁ -C ₅ )alkyl, (C^C^cycloalkanesulfinyl(C ₁ -C ₆ )alkyl, (C ₄ -

C ₈ )cycloalkylalkanesulflnyl(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₈ )alkanesulfinyl(C ₁ -C ₆ )alkyl, halo(C ₃ - C ₈ )cycloalkanesulfinyl(C ₁ -C ₆ )alkyl, halo(C ₄ -C ₈ )cycloalkylalkanesulflnyl(C _l -C ₆ )alkyl, (C ₁ - C ₈ )alkancsulfonyl(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycIoalkanesulfonyl(C ₁ -C ₆ )alkyl, (C ₄ -C ₈ ) cycloalkylalkanesulfonyl(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₈ )alkanesulfonyl(C ₁ -C ₆ )alkyl, halo(C ₃ - C ₈ )cycloalkanesulfonyI(C ₁ -C _fi )alkyl, halo(C ₄ -C ₈ )cycloalkylalkanesulfonyl(C ₁ -C ₆ )alkyl,

(C ₁ -C ₈ )alkylamino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₈ )alkylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkoxycarbonyl(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )acyloxy(C ₁ -C ₆ )alkyl, aminocarbonyl(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl, di(C ₁ -C ₈ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl (C ₁ - C ₈ )acylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkoxycarbonylamino, (C ₁ -C ₈ )alkoxycarbonylamino(C ₁ - C ₆ )alkyl, aminocarboxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl and di(C ₁ - C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl, phenyl, napthyl, hcteroaryl, bicyclic heteroaryl, phenoxy, naphthyloxy, heteroaryloxy, bicyclic heteroaryloxy, phenylthio, naphthylthio, heteroarylthio, bicyclic heteroarylthio, phenylsulfinyl, naphthylsulfinyl, heteroarylsulfinyl, bicyclic heteroarylsulfinyl, phenylsulfonyl, naphthylsulfonyl, heteroarylsulfonyl, bicyclic heteroarylsulfonyl, phenyl(C ₁ -C ₃ )alkyl, napthyl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, and bicyclic heteroaryl(C ₁ -C ₃ )alkyl, wherein the aromatic and heteroaromatic groups are optionally and independently substituted with zero to three groups

- 9 -

selected from: halogen, cyano, (C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ JaIkOXy, halo(C ₁ - C ₃ )alkoxy, (C ₁ -C ₃ )alkanesulfonyl, and (C ₁ -C ₃ )alkoxycarbonyl;

E is a saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ ),, via bonds to two members of said ring, wherein said ring is composed of carbon atoms and zero to four hetcro atoms selected from: zero to four nitrogen atoms, zero or one oxygen atoms, and zero or one sulfur atoms, said ring being optionally and independently substituted with zero to four groups selected from: halogen, hydroxy, (C ₁ -C ₆ )alkyl, (C ₃ - C ₈ )cycloalky[(C ₁ -C ₁ s)alkyl, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, and oxo groups, such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; n is 1 to 3;

G is hydrogen, (C ₁ -C ₆ )alkyl, (C ₄ -C ₇ )heterocyclyl, hydroxy, hydroxy(C ₁ -C ₆ )alkyl, - ^" NR ⁴³ R ⁴ , -O(C ₁ -C ₆ )aIkyl-NR ^4a R ⁴ , amino(C ₁ -C ₆ )alkylcarboxy, (C ₃ -C ₃ )cycloalkyl, (C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkyl., amino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₆ )alkylamino, di(C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkyl, C(=NH)NH ₂ , C(=NH)NHR ⁴ , NHC(=NH)NH ₂ , NHC(=NH)NHR ⁴ ; -(C ₀ -C ₆ )alkyl-NR ⁴ R ^4a , -NHC(=NH)NR ⁴ R ^<fn , -C(=O)(C ₁ -C ₆ )alkyl-NR ⁴ R ^4a , -C(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₄ )alkylaryl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl,

-(C ₁ -C ₄ )alkyl(C ₃ -C ₃ )cycloalkyl, or -(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, wherein the moiety is optionally substituted by amino, hydroxy, or (C[-C ₃ )alkylamino; and where R ^4a is H or (C ₁ -C ₃ )alkyl and R ⁴ is selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₆ )alkyl, and (C ₄ -C ₇ )heterocyclyl(C ₁ -C ₆ )alkyl, or R ⁴ and R ^4a , taken together with the nitrogen atom to which they are attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1 -3 heteroatoms selected from 1 , 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, amino, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl,, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; or an enantiomer, diastereomer or pharmaceutically acceptable salt thereof.

In another embodiment the present invention is directed to pharmaceutical compositions comprising a compound described herein or enantiomers, diastereomers, or salts thereof and a pharmaceutically acceptable carrier or excipicnt.

- 10 -

In another embodiment the present invention is directed to a method of antagonizing aspartic protease inhibitors in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound described herein or an enantiomer, diastereomer, or salt thereof, In another embodiment the present invention is directed to method for treating or ameliorating an aspartic protease mediated disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound described herein or an enantiomer, diastereomer, or salt thereof.

In another embodiment the present invention is directed to a method for treating or ameliorating a renin mediated disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound described herein or an enantiomer, diastereomer, or salt thereof.

In another embodiment the present invention is directed to a method for the treatment of hypertension in a subject in need thereof comprising administering to the subject a compound described herein in combination therapy with one or more additional agents said additional agent selected from the group consisting of α-blockers, β-blockers, calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, dual ACE and neutral endopeptidase (NEP) inhibitors, angiotensin-receptor blockers (ARBs), aldosterone synthase inhibitors, aldosterone- receptor antagonists, and endothelin receptor antagonists.

DETAILED DESCRIPTION OF THE INVENTION

A description of embodiments of the compounds of Formula I of the invention follows. It is understood that the invention encompasses all combinations of the substituent variables (i.e., R, R ¹ , R ² , R ³ , etc.) defined herein. Values and particular values for the variables in Formula I are provided in the following paragraphs. In one embodiment of this invention, R is (1) hydrogen; (2) (C ₁ -C ₈ )alkyl _J (C ₂ -C ₈ )alkenyl,

(C ₂ -C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ - C ₇ )cycloalkyl(C ₂ -C ₃ )alkenyl, (C ₃ -C ₇ )cycloalkyl(C ₂ -C ₃ )alkynyl, (C ₁ -C ₈ )alkoxy, (C ₃ -C ₈ )alkenyloxy, (C ₃ -C ₈ )alkynyloxy, (C ₃ -C ₇ )cycloalkoxy, (C ₅ -C ₇ )cycloalkenyloxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalky 1(C ₁ -COaIkOXy, (C ₅ -C ₇ )cycloalkenyl(C ₁ -C ₃ )alkoxy, (C ₁ -C ₈ )alkylthio, (C ₃ - C ₈ )alkenylthio, (C ₃ -C ₈ )alkynylthio, (C ₃ -C ₇ )cycIoalkylthio(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ - C ₃ )alkylthio, (C ₅ -C ₇ )cycloalkenyl(C ₁ -C ₃ )alkylthio, (C ₁ -C ₈ )alkylamino, di(C ₁ -C ₈ )alkylamino, azepano, azetidino, piperidino, pyrrolidine, (C ₃ -C ₇ )cycloalkylamino, ((C ₃ -C ₇ )cycloalkyl(C ₁ - C ₃ )alkyl)amino, or tri(C ₁ -C ₄ )alkylsilyl, each optionally and independently substituted with zero to four substituents selected from the group consisting of halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ - C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )cycloalkoxy and oxo; (3) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, ary)(C ₁ -C ₃ )alkoxy, heteroaryl(C ₁ -C ₃ )alkoxy, aryl(C ₂ -C ₃ ))alkenyl, aryl(C ₂ -C ₃ )alkynyl, heteroaryl(C ₂ -C ₃ )alkenyl, or

- 1 1 -

heteroaryl(C ₂ -C ₃ )alkynyl, each optionally and independently substituted with zero to three substituents selected from the group consisting of: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (G,-C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )- cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, haIo(C ₃ -C ₆ )cycloalkyl _s halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ - Qs)cycloalkoxy, halo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ - C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkythio, halo(G,- C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyi, (C ₃ -C ₆ )cycloalkanesulfinyl, (C ₄ - C ₇ )cycloalkylalkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ - C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -

C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyI, halo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ - C ₇ )cyclo-alkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₃ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, H ₂ NCO, H ₂ -NSO ₂ , (C ₁ - C ₆ )alkylaminocarbonyl, and di(C ₁ -C ₆ )alkylaminocarbonyl, (C ₁ -C ₆ )alkylaminosulfonyl, and di(C ₁ - C ₆ )alkylaminosulfonyl; or (4) a divalent radical selected from -(CHi) ₃ -, -(CH ₂ ) ₄ -, -(CH ₂ )s- or - (CH ₂ ) ₆ -, which is attached to R ¹ to form a fused or spirofused ring system, and is optionally and independently substituted with zero to four substituents selected from: halogen, hydroxy, (C ₁ - C ₆ )alkyl, halo(C ₁ -C ₆ )alkyI, (C ₁ -C ₆ )alkoxy and oxo.

In a particular embodiment of this invention, R is (1) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ - C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ - C ₇ )cycloaIkyl(C ₂ -C ₃ )alkenyl _s (C ₃ -C ₇ )cycloaIkyl(C ₂ -C ₃ )alkynyl, (C ₁ -C ₈ )-alkoxy, (C ₃ - C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycIoalkoxy(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkoxy, (C ₁ - C ₈ )alkylthio, (C ₃ -C ₇ )cycloalkylthio, (C ₃ -C ₇ )cycloalkylthio(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ - C ₃ )alkylthio, azepano, azetidino, piperidino, pyrrolidino or tri(CpC ₄ )alkylsilyl, each optionally substituted with up to four substituents independently selected from the group consisting of: fluorine, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₁ - C _f i)cycloalkoxy, and oxo; or

(2) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C ₁ -C ₃ )alkyl, heteroaryI(C ₁ -C ₃ )alkyI, aryl(C ₁ -C ₃ )alkoxy, heteroaryl(C ₁ -C ₃ )alkoxy, arylethenyl, heteroarylethenyl, or arylethynyl, heteroarylethynyl, each optionally substituted with up to three substituents independently selected from the group consisting of: fluorine, chlorine, cyano, (C ₁ -C ₆ )alkyl, (Cj-CβJcycIoalkyl, halo(C ₁ - C ₆ )alkyl, halo(C ₃ -C ₆ )cycloaIkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cyclo-alkylalkoxy, halo(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkanesulfinyl, halo(C ₁ - C ₆ )alkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, H ₂ NCO, H ₂ NSO ₂ , (C ₁ - C ₆ )alkylaminocarbonyl, and (C ₁ -C ₆ )alkylaminosulfonyl; or

(3) R is a divalent radical selected from -(CHj) ₄ - or -(CH ₂ ) ₅ -, which is attached to R ¹ to form a fused or spirofused ring system, and is optionally substituted with up to four substituents

- 12 -

independently selected from: fluorine, hydroxy, (C ₁ -C ₆ )BIlCyI, HaIo(C ₁ -C ₆ )SIlCyI, (C ₁ -C ₆ )alkoxy and oxo.

In another particular embodiment, R is (1) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₃ -C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkylethenyl, (C ₃ - C ₇ )cycloalkylethynyl, (C ₁ -C ₈ )alkoxy, (C ₃ -C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ - C ₇ )cycloalkyl(C ₁ -C ₃ )alkoxy, piperidino, pyrrolidino or tri(C ₁ -C ₃ )alkylsilyl, each optionally substituted with up to 4 substituents independently selected from fluorine, hydroxy, (C ₁ -C ₃ )alkyl, and halo(C ₁ -C ₃ )alkyl, or (2) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C ₁ -C ₃ )alkoxy, or monocyclic heteroaryl(C ₁ -C ₃ )alkoxy, each optionally substituted with up to three substituents independently selected from halogen, cyano, (C ₁ -C ₃ )alkyl, (C ₃ -C ₅ )cycloalkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkylthio, and H ₂ NCO; or (3) a divalent radical selected from -(CH ₂ ) ₄ - or -(CHj) ₅ -, which is attached to R ¹ to form a fused or spirofused ring system.

In a further particular embodiment of this invention, R is (1) (C ₁ -C ₇ )alkyl, (C ₃ - C ₇ )cycloalkyl, (C ₅ -C ₇ )cycloalkenyl, (C ₁ -C ₇ )alkoxy, (C ₃ -C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycloalkyl(C ₁ - C ₃ )alkoxy, piperidino, pyrrolidino or tri(C ₁ -C ₃ )alkylsilyl, each optionally substituted with up to 4 substituents independently selected from fluorine, hydroxy, (C ₁ -C ₃ )alkyl, and halo(C ₁ -C ₃ )alkyl; or (2) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C ₁ -C ₃ )alkoxy, and monocyclic heteroaryl(C ₁ -C ₃ )alkoxy, each optionally substituted with up to 3 substituents independently selected from fluorine, chlorine, cyano, (C ₁ -C ₃ )alkyl, (C ₃ -C,i)cycloalkyl, halo(C ₁ - C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkylthio, and H ₂ NCO; or (3) -(CH ₂ J ₄ - or -(CH ₂ ) ₅ -. In specific embodiments of this invention, R is ethyl, isobutyl, t-butyl, 2,2-dimethyl-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2-(cyclopropyl)ethoxy, cyclobutylmethόxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chIorophenyI, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5- dimethylphenyl, 5-methyl-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophcnoxy, 2- chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3-fluorophenoxy, 3-methylphenoxy, 4- fluorophenoxy, 4-methylphenoxy, 2-methyl-4-fluorophenoxy, 2-methyl-5-fluorophenoxy, or piperidino, trimethylsilyl, -(CH ₂ ) ₄ - or -(CH ₂ ) ₅ -.

R ¹ is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-l ,3-dioxole, benzo-1 ,3- dioxine, 2,3-dihydrobenzo-l,4-dioxine or (C ₃ -C ₇ )cycloalkyl, each optionally and independently substituted with zero to four substituents selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (G,-C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ -C ₆ )- cycloalkyl(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ -

- 13 -

C ₆ )cycloalkoxy, haIo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkythio, (C ₄ - C ₇ )cycloalkylalkylthio, ha!o(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkythio, halo(C ₄ - C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ -C ₆ )cycloalkanesulflnyl, (C ₄ - C ₇ )cycloalkylalkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₃ )cycloalkanesulfinyI, halo(C ₄ - C^cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ -

C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, haIo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ - C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, H ₂ NSO ₂ , H ₂ IWCO, (C ₁ - C ₆ )alkylaminosulfonyl, di(C ₁ -C ₆ )alkylaminosulfonyl, (CpC ₆ )alkylaminocarbonyl and di(C ₁ - C ₆ )alkylaminocarbonyl.

In a particular embodiment of this invention, R ¹ is a phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-1 ,3-dioxole, or (C ₃ -C ₇ )cycloalkyl ring optionally substituted with up to four substituents independently selected from the group consisting of: fluorine, chlorine, bromine, cyano, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cyc1oalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ - C ₆ )alkyithio, (C ₁ -C ₆ )alkanesulfinyl, haio(C ₁ -C ₆ )alkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, halo(C ₁ - C ₆ )alkanesulfonyl, H ₂ NSO ₂ , H ₂ NCO, (C ₁ -C ₃ )alkylaminosulfonyl, and (C ₁ -C ₃ )alkylaminocarbonyl.

In another particular embodiment of this invention, R ¹ is a phenyl, monocyclic heteroaryl ring, bicyclic heteroaryl ring or benzo-1 , 3-dioxole, optionally substituted with up to four substituents independently selected from: halogen, cyano, (C ₁ -C ₃ )alkyl, (C ₃ -C ₄ )cycloalkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, and H ₂ NCO. In a further embodiment of this invention, R ¹ is a phenyl, furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, thiazole, pyridine, pyrimidine, pyrazine, benzofuran, benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, quinazoline or benzo-1 , 3-dioxole, each optionally substituted with up to 3 substituents independently selected from fluorine, chlorine, cyano, (C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ - C ₃ )alkoxy, and carboxamide. In specific embodiments of this invention, R ¹ is phenyl, 2- fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluoroρhenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, benzofuran, benzothiophene, benzoxazole, benzo-1 , 3-dioxole. R ² is hydrogen or (C ₁ -C ₁₂ )alky I, (C ₂ -C ₁₂ )alkenyl, (C ₂ -C ₁₂ )alkynyl, (C ₁ -C ₁₂ )alkoxy, (C ₁ - C ₁₂ )alkylthio, (C ₁ -C ₁₂ )alkylamino, oxo(C ₁ -C ₁₂ )alkyl, oxo(C ₂ -C ₁₂ )alkenyl, oxo(C ₂ -C ₁₂ )alkynyl, oxo(C ₁ -C ₁₂ )alkoxy, oxo(C ₁ -C ₁₂ )alkylthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₃ )alkyl, (C ₁ - C ₆ )alkylthio(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino(C ₁ -C ₃ )alkyI, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )aIkoxy, (C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyIamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylthio(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₄ )alkoxy(C ₁ - C ₄ )alkoxy(C ₁ -C ₄ )alkyl, aminocarbonylamino(C ₁ -C ₁₂ )alkyl, aminocarbonylamino(C ₁ -C ₁₂ )alkoxy, aminocarbonylamino(C ₁ -C ₁₂ )alkylthio, aminocarbonylamino(C ₁ -C ₁₂ )alkyIamino, (C ₁ -

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C ₆ )alkanoylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkanoylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )alkanoylaiτiino(C ₁ -C ₆ )aIkylamino, (C ₁ -C ₅ )alkoxycarbonyl(C ₁ -C ₆ )alk ^' yl, (C ₁ - C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkylamino, aminosulfonylamino(C ₁ - C ₁₂ )alkyl, aminosulfonylamino(C ₁ -C ₁₂ )alkoxy, aminosulfonylamino(C ₁ -C ₁₂ )alkylthio, aminosulfonyIamino(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylamino, formylamino(C ₁ -C ₆ )alkyl, formylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ -C ₆ )alkylthio, formylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyIamino(C ₁ -

C ₆ )alkyl, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyIamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkylamino, aminocarbonyl(C ₁ -C ₆ )alkyl, aminocarbonyl(C ₁ - C ₆ )alkoxy, aminocarbonyl(C ₁ -C ₆ )alkylthio, aminocarbonyl(C ₁ -C ₆ )alkylamino; (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkylthJo, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkyamino, aminocarboxy(C ₁ -C ₆ )alkyl, aminocarboxy(C ₁ -C ₆ )alkoxy, aminocarboxy(C ₁ -C ₆ )alkylthio, aminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₁₂ )alkoxycarbonylamino, (C ₁ - C ₁₂ )alkylaminocarbonylamino, or (C ₁ -C ₁₂ )alkanoylamino, each optionally substituted by (1 ) I to 5 halogen atoms; and (2) 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₆ )cycloalkyl, and halo(C ₃ -C ₆ )cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to a thiocarbonyl groups.

In a particular embodiment of this invention, R ² is (1) hydrogen or (2) (C ₁ -C ₁₀ )alkyl, (C ₂ - C ₁₀ )alkenyl, (C ₂ -C ₁₀ )alkynyl, (C ₁ -C ₁₀ )alkoxy, (C ₁ -C ₁₀ )alkylthio, (C ₁ -C ₁₀ )alkylamino, (C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkyl, (C ₁ -

C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )aIkoxy(C ₁ -C ₅ )alkylamino, (C ₁ - C ₅ )alkylthio(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkyIthio(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ - C ₅ )alkylamino, (C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkyl, aminocarbonylamino(C ₁ -C ₁₀ )alkyl, aminocarbonylamino(C ₁ -C ₁₀ )alkoxy, aminocarbonylamino-(C ₁ -C ₁₀ )alkylthio, aminocarbonylamino(C ₁ -C ₁₀ )aIkylamino, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₃ )alkylthio, (C ₁ -C ₅ )- alkanoylamino(C ₁ -C ₅ )alkylamino, aminosulfonylamino(C ₁ -C _l0 )alkyl, aminosulfonylamino(C ₁ -

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C ₁₀ )alkoxy, aminosulfonylamino^i-C^)alkylthio, aminosulfonylamino(C ₁ -C ₁₀ )alkylamino, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkylthio _: , (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkylamino, formyIamino(C ₁ -C ₅ )alkyl, formylamino(C ₁ -C ₃ )alkoxy, formylamino(C ₁ -C ₃ )alkylthio, formylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )aIkyl, (C ₁ -C ₅ )alkoxy- carbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₃ )alkylthio, (C ₁ -C ₅ )alkoxy- carbonylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkyl _J (C ₁ - C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarbonyIamino(C ₁ -C ₅ )alkylamino, aminocarbony)(C ₁ -C ₅ )aIkyl, aminocarbonyl(C ₁ -C ₅ )aIkoxy, aminocarbonyl(C ₁ -C ₅ )alkylthio, aminocarbonyl(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )aIkylaminocarbonyl(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkytaminocarbonyl(C ₁ -C ₅ )alkyamino, aminocarboxy(C ₁ -C ₅ )alkyl, aminocarboxy^-C ₅ )alkoxy, aminocarboxy(C ₁ -C ₅ )alkylthio, aminocarboxy(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylamino- carboxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ - C ₅ )alkylamino, (C ₁ -C ₁₀ )alkoxycarbonylamino, (C ₁ -C ₁₀ )alkylaminocarbonylamino, or (C ₁ -C ₁₀ )- alkanoylamino, wherein (1 ) each are optionally substituted by (a) 1 to 5 fluorine atoms and (b) by 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -C ₄ )cycloalkyl, (C ₃ - C ₄ )cycloalkoxy _s haIo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₄ ,)cycloalkyl, and halo(C ₃ - • C. ₄ )cycloalkoxy and wherein (2) divalent sulfur atoms are optionally oxidized to sulfoxide or sulfone.

In another particular embodiment of this invention, R ² is hydrogen, (C ₁ -C ₈ )alkyl, (C ₄ - C ₉ )cycloalkylalkyl, fluoro(C ₁ -C ₈ )alkyl, fluoro(C ₄ -C ₉ )-cycloalkylalkyl, (C ₁ -C ₈ )alkoxy, (C ₄ - C ₉ )cycloalkylalkoxy, fluoro(C ₁ -C ₈ )alkoxy, hydroxy(C ₁ -C ₈ )alkyl, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkyl, haIo(C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )hydroxyalkyl, (C ₃ -C ₄ )cycloalkoxy(C ₁ - C ₅ )alkyl, fluoro(C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkyl, fluorp(C ₃ -C ₄ )cycloalkoxy(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkyIthio(C ₁ -C ₅ )alkyI, (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkoxy, hydroxy(C ₁ -C ₈ )alkoxy, (C ₃ - C ₄ )cycloalkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -C ₅ )aIkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₃ -C ₄ )cycloalkoxy(C ₁ - C ₅ )alkoxy, (C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkyl, fluoro(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ - C ₃ )alkyl, aminocarbonylamino(C ₁ -C ₈ )alkyI, aminocartonylamino(C ₁ -C ₈ )alkoxy, (C ₁ - C ₅ )alkanoyIamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -

C ₅ )alkanoylamino(C ₁ -C ₅ )alkyl, fluoro(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkoxy(C ₁ - C ₅ )alkanoylamino(C ₁ -C ₅ )aIkyl, (C ₁ -C ₃ )alkoxy(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₃ -C ₄ )- cycloalkanecarbonyllamino(C ₁ -C ₅ )alkyl, ^^^ycloalkanecarbonyllaminotC ₁ -C ₅ )alkoxy, aminosulfonylamino(C ₁ -Cs)alkyl, aminosulfonylamino(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkane- ^• sulfonylamino(C ₁ -C ₅ )alkyl, (C ₁ -Cj)alkanesulfonylamino(C ₁ -C ₅ )alkoxy, formylamino(C ₁ -C ₅ )alkyl, formylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxycarbonyl- amino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )aIkylaminocarbonylamino(C ₁ -Cj)alkyl, (C ₁ -C ₅ )alkylamino- carbonylamino(C ₁ -C ₅ )alkyl, di(C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, aminocarbonyl(C ₁ -

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C ₅ )alkyl, aminocarbonyl(C ₁ -C ₅ )alkoxy, (C ₁ -Cj)alkylaminocarbonyl(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy, aminocarboxy(C ₁ -C ₃ )alkyl, aminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkyIaminocarboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )aIkylamino-carboxy(C ₁ -C ₅ )alkoxy, (C ₁ - C ₈ )alkoxycarbonylamino, (C ₁ -Csjalkylaminocarbonylamino, (C ₁ -C ₈ )alkanoylamino, fluoro(C ₁ - C ₈ )alkoxycarbonylamino, fluoro(C ₁ -C ₈ )alkylaminocarbonylamino, or fluoro(C ₁ -C ₈ )alkanoylamino. In a further particular embodiment of this invention, R ² is (C ₁ -C ₃ )aIkoxy(C ₁ -C ₅ )alkyl, (C ₁ - C ₃ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₃ -C ₄ )cycIoalkyl(C ₁ -C ₅ )alkyl, (C ₃ ~C ₄ )cyc]oalkyl(C ₁ -C ₅ )alkoxy, (C ₁ - C ₃ )alkoxycarbonylamino(C ₁ -Q)alkyl, (C ₁ -C ₃ )-alkoxycarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₃ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )-alkanoylamino(C ₁ -C ₃ )alkoxy, (C ₁ - C ₃ )alkylaminocarbonyl(C ₁ -C ₅ )alkyl or (C ₁ -C ₃ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy. In specific embodiments of this invention, R ² is 4-methoxybutyl, 4-ethoxybutyl, 4-methoxypentyl, 3- methoxypropoxy, 3-(methoxycarbonyIamino)propyl, 3-(acetylamino)propyl, 2- (acetylamino)ethoxy, or 2-(methoxycarbonylamino)ethoxy.

R ³ is hydrogen, halogen, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkoxy, hydroxyl, hydroxy(C ₁ -C ₆ )alkyl, hydro xy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino, (C ₁ -C ₆ )alkoxycarbonylamino, (C ₁ -

C ₆ )alkylaminocarbonylamino, di(C ₁ -C ₆ )alkylaminocarbonylamino, (C ₁ -C ₆ )alkanesulfonylamino, (C ₁ -C ₆ )alkylaminosulfonylamino, di(C ₁ -C ₆ )alkylaminosulfonylamino, phenylamino or heteroarylamino in which each phenylamino or heteroary [amino group is optionally substituted with I to 5 groups independently selected from the group consisting of halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C _fi )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ -C ₆ )alkynyl, (C ₃ - C ₆ )-cycloalkyi(C ₂ -C ₄ )aIkynyl, halo(C ₁ -C ₆ )alkyl, haIo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ -C ₇ )cycIoalkyIalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (G,-C ₇ )cyc]oalkylalkoxy, halo(C ₁ -C ₆ )alkoxy, halo(C ₃ - C ₆ )cycloalkoxy, halo(C ₄ -C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkylthio, (C ₃ -C ₆ )cycloalkylthio, (C ₄ - C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkylthio, halo(C ₄ - C ₇ )cycloalkylalkylthio, (C ₁ -C ₆ )alkanesulfinyl, (C ₃ -C ₆ )cycloalkanesulfinyl, (C ₄ -

C ₇ )cycloalkylalkanesulfinyl, haIo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₆ )cycloalkanesulfinyl, halo(C ₄ - C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ - C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, halo(C ₃ -C ₆ )cycloalkanesulfonyl, halo(C ₄ - C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, aminocarbonyl, (C ₁ -

C ₆ )alkylaminocarbonyl, and di(C ₁ -C ₆ )alkylaminocarbonyl; provided that R ² and R ³ are not both hydrogen; and when R ³ is hydroxy, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ -C ₁₂ )alkoxy, (C ₁ -C ₁₂ )alkylamino, oxo(C ₁ - C ₁₂ )alkoxy, oxo(C ₁ -C ₁₂ )alkylthio, oxo(C ₁ -C ₁₂ )alkylamino, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkoxy(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylthio(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylthio(C ₁ -C6)alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )aIkoxy, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyIamino, aminocarbonylamino(C ₁ - C ₁₂ )alkoxy, aminocarbbnylamino(C ₁ -C _|2 )alkylthio, aminocarbonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ -

- 17 -

C ₆ )alkanoylamino(C _l -C ₆ )alkoxy, (C ₁ -C ₆ )alkanoylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkanoylamino(C ₁ - C ₆ )alkylamino, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylthio, (C ₁ -C ₆ )alkoxycarbonyl(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ ) acyloxy(C ₁ -C ₁ ;)aIkoxy, (CpC ₆ ) acyloxy(C ₁ - C ₆ )alkylthio, (C ₁ -C ₆ )acyloxy(C ₁ -C ₆ )alkyIamino, aminosulfonylamino(C ₁ -C ₁₂ )alkoxy, aminosulfonylamino(C ₁ -C ₁₂ )alkylthio, aminosulfonylamino(C ₁ -C ₁₂ )alkylamino, (C ₁ - C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkanesulfonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkanesu]fonylamino(C ₁ -C ₆ )alkylamino, fortnylamino(C ₁ -C ₆ )alkoxy, formylamino(C ₁ - C ₆ )alkylthio, fOrmylamino(C _| -Q;)alkyIamino, (C ₁ -Qøalkoxycarbonylamino^i-C ₆ )alkoxy, (C ₁ - C ₆ )alkoxycarbonylamino(C ₁ -C ₆ )alkylthio, (C ₁ -C _fi )alkoxycarbonylamino(C ₁ -C ₆ )alkylamino ₁ (C ₁ - C ₆ )alkylaminocarbonyIamino(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkyIaminocarbonylamino(C ₁ -C ₆ )alkylthio, (C ₁ - C ₆ )alkylaminocarbonylamino(C ₁ -C ₆ )alkylaminQ, aminocarbonyl(C ₁ -C ₆ )alkoxy, aminocarbonyl(C ₁ - C ₅ )alkylthio, aminocarbonyi(C ₁ -C ₆ )alkylamino, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkoxy, (C ₁ - C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )aIkylthio, (C ₁ -C ₆ )alkylaminocarbonyl(C ₁ -C ₆ )alkylamino, aminocarboxy(C ₁ -C ₆ )alkoxy, aminocarboxy(C ₁ -C ₆ )alkylthio, aminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ - C ₆ )aIkylaminocarboxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylaminocarboxy(C ₁ -C _fi )alkylthio _J (C ₁ - C ₆ )alkylaminocarboxy(C ₁ -C ₆ )alkylamino, (C ₁ -C ₁₂ )alkoxycarbonylamino, (C ₁ - C( ₂ )alkylaminocarbonylamino, or (C ₁ -C _{1 2} )alkanoylamino, each optionally substituted by: (1 ) 1 to 5 halogen atoms; and (2) 1 group selected from cyano, hydroxy, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ - C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₆ )cycloalkyl, or halo(C ₃ -C ₆ )cycloalkoxy; wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to thiocarbonyl groups.

In another particular embodiment of this invention, R ³ is H, halogen, (CpC ₃ )alkyl, (C ₁ - C ₃ )alkoxy, hydroxyl, hydroxy(C ₁ -C ₃ )alkyI, hydroxy(C ₁ -C ₃ )alkoxy, (C ₁ -C ₄ )alkanoylamino, (C ₁ - C ₃ )alkoxycarbonylamino, (C ₁ -C ₃ )alkyiamino-carbonylamino, di(C ₁ -C ₃ )alkylaminocarbonylamino, (C ₁ -C ₃ )alkanesulfonylamino, (C ₁ -C ₃ )alkylaminosulfonylamino, di(C ₁ -C ₃ )alkylaminosulfonylamino, or phenylamino or heteroarylamino in which each phenylamino and heteroarylamino group is optionally substituted with 1 to 3 groups independently selected from: fluorine, chlorine, cyano, (C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkanesulfonyl, and (C ₁ -C ₃ )alkoxycarbonyl; provided that (i) R ² and R ³ are not both hydrogen and (ii) when R ³ is hydroxyl, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ - C ₁₀ )alkoxy, (C ₁ -C ₁₀ )alkylthio, (C ₁ -C _!0 )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkyltriio, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkylamino, (C _r Cj)alkyIthio(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ - C ₅ )alkylamino, aminocarbonyIamino(C ₁ -C ₁₀ )alkoxy, aminocarbonylamino(C ₁ -C ₁₀ )alkylthio, aminocarbonyl-amino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkanoylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkylamino,

- 18 -

aminosulfonylamino(C ₁ -C ₁₀ )alkoxy, aminosulfonylamino(C ₁ -C ₁₀ )alkylthio, aminosulfonylamino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )-alkanesulfonylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkanesu]fonylamino(C _| -C ₅ )alkylthio, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkylamino, formylamino(C ₁ -C ₅ )alk.oxy, formylamino(C ₁ -C ₅ )alkyIthio, formylamino(C ₁ -C ₅ )alkylamino, (C ₍ - C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )aIkoxycarbonyIamino(C ₁ -C ₅ )alkylthio, (C ₁ - C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkylamino, aminocarbonyl(C ₁ -C ₃ )alkoxy, aminocarbonyl(C ₁ -C ₅ )alkylthio, aminocarbonyl(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarbonyl-(C ₁ -C ₅ )alkoxy, (C ₁ -Cj)alkylaminocarbonyl(C ₁ -C ₅ )alkylthio, (C ₁ - C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkyamino, aminocarboxy(C ₁ -C ₃ )alkoxy, aminocarboxy(C ₁ - C ₅ )alkylthio, aminocarboxy(C ₁ -C ₅ )aIkylamino, (C ₁ -QOalkylaminocarboxy^i-C ₅ ^lkoxy, (C ₁ - C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkyIaminocarboxy(C ₁ -C ₅ )aIkyiamino, (C ₁ - C ₁₀ )alkoxycarbonylamino, (C ₁ -Qojalkylaminocarbonylamino, or (C _l -C ₁ o)alkanoylamino, wherein (1) each arc optionally substituted by (a) 1 to 5 fluorine atoms and (b) by I group selected from cyano, hydroxy), (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -C ₄ )cycloalkyl, (C ₃ -C ₄ )cycloalkoxy, halo(C ₁ - C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -G,)cycloalkyl, and halo(C ₃ -C ₄ )cyc)oalkoxy and wherein (2) divalent sulfur atoms are optionally oxidized to sulfoxide or stilfone.

In a further particular embodiment of this invention, R ³ is H, halogen, OH, (C ₁ - C ₄ )alkanoylamino, or (C ₁ -C ₃ )alkoxy; provided that (i) R ² and R ³ are not both hydrogen and (ii) when R ³ is OH or halogen, R ² is not (C ₁ -C ₈ )alkoxy, (C ₄ -C ₈ )cycloalkylalkoxy, fluoro(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, hydroxy(C ₁ -C ₈ )alkoxy _s (C ₃ -C ₄ )cycloalkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, fluoro(C ₃ -C ₄ )cycloalkoxy(C ₁ -C ₅ )alkoxy, aminocarbonylamino(C ₁ - C ₈ )alkoxy, (C ₁ -C ₅ )-aIkanoylamino(C ₁ -C ₅ )alkoxy, fluoro(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₃ )alkoxy(C ₁ -C ₅ )alkanoylamino(C ₁ -C ₅ )alkoxy, (C ₃ -C ₄ )cycloalkanecarbonyllamino(C ₁ -C ₅ )alkoxy, aminosulfonylamino(C ₁ -C ₈ )alkoxy, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkoxy, formylamino(C ₁ - C ₅ )alkoxy, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₃ )alkoxy, di(C ₁ -C ₅ )alkylaminocarbonylamino(C ₁ - C ₅ )alkoxy, aminocarbonyl(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy, aminocarboxy(C ₁ -C.s)alkoxy, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkoxy, (C ₁ -C ₈ )alkoxy- carbonylamino, (C ₁ -C ₈ )alkylaminocarbonylamino, (C ₁ -C ₈ )alkanoylamino, fluoro(C ₁ -C ₈ )alkoxy- carbonylamino, fluoro(C ₁ -C ₈ )alkyIaminocarbonylamino, or fluoro(C ₁ -C ₈ )alkanoylamino. In specific embodiments of this invention, R ³ is hydrogen or hydroxy I provided that when R ³ is hydroxyl, R ² is not 3-methoxypropoxy, 2-(acetylamino)ethoxy, or 2-( methoxycarbonylamino)ethoxy.

A is a saturated or unsaturated 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ ) _m via bonds to two members of said ring, wherein said ring is composed of carbon atoms and 0- 2 hetero atoms selected from the group consisting of 0, 1 , or 2 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or I sulfur atoms, said ring being optionally and independently substituted with zero to four halogen atoms, (C ₁ -C ₆ )alkyl groups, halo(C ₁ -C ₆ )alkyl groups or oxo groups such that when there is

- 19 -

substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively.

Q and Y are attached to carbon or nitrogen atoms in ring A in a 1 ,2- or 1 ,3-, or 1 ,4- relationship; X and Y are each independently CH ₂ or a single bond. In the specific embodiments of this invention, X and Y are each a single bond.

In one particular embodiment of this invention, Q is a divalent radical selected from

v° ιr ^NOϊ i ^CN Vf°

Q1 Q2 Q3 Q4 Q5 Q6

wherein A and E are attached to the truncated bonds

Q7 Q8 Q9 Q10

In another particular embodiment of this invention, Q is a divalent radical selected from Q1 , Q2, Q3, Q4, Q5, Q6, and Q7. In another embodiment of this invention, Q is Q l , Q2, Q4, or Q6. In specific embodiments of this invention, Q is Q1, Q4, or Q6.

W is a bond or a (C ₁ -C ₆ )alkylene, and W is optionally and independently substituted by zero to four groups selected from: ( I) (C ₁ -C ₁₂ )alkyl, (Q-C ₈ icycloalkyl, (C ₃ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₂ -C ₁₂ )alkenyl, (C ₅ -C ₈ )cycloalkyl(C ₁ -C ₃ )alkenyl, (C ₁ -C ₁₂ )alkynyl, (C ₃ -C ₈ )cycloalkyl(C ₁ - C ₃ )alkynyl, (C ₄ -C ₁₂ )bicycloalkyl(C ₁ -C ₃ )alkyl, (C ₈ -C ₁₄ )tricycloalkyl(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₁ -C ₆ )alkylthio(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkylthio(C ₁ - C ₃ )alkyl, saturated heterocyclyl, saturated heterocyclyl(C ₁ -C ₃ )alkyI, hydroxy and oxo wherein: (a) hydrogen atoms in these groups are optionally and independently substituted by zero to six groups selected from: halogen, cyano, hydroxy, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, (C ₃ -C ₆ )cycloalkyl, (C ₃ - C ₆ )cycloalkoxy, halo(C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₃ -C ₆ )cycloalkoxy and wherein (b) divalent sulfur atoms are optionally oxidized to sulfoxide or sulfone. or (2) phenyl, naphthyl, heteroaryl, phenyl(C ₁ -C ₃ )alkyl, naphthyl(C ₁ -C ₃ )alkyl, and heteroaryl(C ₁ -C ₃ )alkyl, each optionally and independently substituted with zero to three groups selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₄ -C ₇ )cycloalkylalkyl, (C ₂ - C ₆ )alkynyl, (C ₃ -C ₆ )cycloalkyl-(C ₂ -C ₄ )alkynyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, halo(C ₄ - C ₇ )cycloalkylalkyl, (C ₁ -C ₆ )alkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, halo(C ₁ - C ₆ )alkoxy, halo(C ₃ -C ₆ )cydoalkoxy, halo(G,-C ₇ )cycloalkylalkoxy, (C ₁ -C ₆ )alkylthio ₃ (C ₃ - C ₆ )cycloalkylthio, (C ₄ -C ₇ )cycloalkylalkylthio, halo(C ₁ -C ₆ )alkylthio, halo(C ₃ -C ₆ )cycloalkylthio, halo(C ₄ -C ₇ )cycloalkylaIkylthio, (C ₁ -C ₆ )alkancsulfinyl, (C ₃ -C ₆ )cycloalkanesulfinyl, (C ₄ - C ₇ )cycloalkylalkanesulfinyl, haIo(C ₁ -C ₆ )alkanesulfinyl, halo(C ₃ -C ₃ )cycloalkanesulfinyl, halo(C ₄ -

- 20 -

C ₇ )cycloalkylalkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, (C ₃ -C ₆ )cycloalkanesulfonyl, (C ₄ - C ₇ )cycloalkylalkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, halo(C ₃ -Q)cycloalkanesulfonyl, halo(C ₄ - C ₇ )cycloalkylalkanesulfonyl, (C ₁ -C ₆ )alkylamino, di(C ₁ -C6)aIkylamino, (C ₁ -C ₆ )alkoxy(C ₁ - C ₆ )alkoxy, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkoxycarbonyl, aminocarbonyl, (C ₁ - C ₆ )alkylaminocarbonyl, di(C ₁ -C _fi )alkylaminocarbonyl, cyano(C ₁ -C ₆ )alkyI, hydroxy(C ₁ -C ₆ )alkyl, carboxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkoxy(C ₁ -C _fi )aIkyl, (C ₄ - C ₈ )cycloalkyIalkoxy(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkoxy(C ₁ - C ₆ )alkyl, halo(C ₄ -C ₈ )cycIoalkyialkoxy(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylthio(C ₁ -C ₃ )alkyl, (C ₃ - C _H )cycloalkylthio(C ₁ -C ₆ )alkyl, (C ₄ -C ₈ )cycloalkyIalkylthio(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₃ )alkylthio(C ₁ - C ₆ )alkyl, halo(C ₃ -C ₈ )cycloalkylthio(C ₁ -C ₆ )alkyl, halo(C ₄ -C ₈ )cycloalkylalkylthio(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkanesulfinyl(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkanesuirinyl(C ₁ -C ₆ )alkyl, (C ₄ - C ₈ )cycloaIkyIalkanesu!finyl(C ₁ -C ₆ )aIkyl, halo(C ₁ -C ₈ )alkanesulfinyl(C _l -C ₅ )alkyl, halo(C ₃ - C ₈ )cyc]oalkanesulfinyl(C ₁ -C ₆ )alkyl, halo(C ₄ -Cs)cycloalkylalkanesulfinyl(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkanesuIfonyl(C ₁ -C ₆ )aIkyl, (C ₃ -C ₈ )cyc]oalkanesulfonyl(C ₁ -C ₆ )alkyl ₁ (C ₄ -C ₈ ) cycIoalkylaIkanesuIfonyl(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₈ )alkanesulfonyl(C ₁ -C ₆ )alkyl, halo(C ₃ - C ₈ )cycloaIkanesulfonyl(C ₁ -C ₆ )alkyl, halo(C ₄ -Ca)cycloalkylalkanesulfonyl(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkylamino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₈ )alkylamino(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkoxycarbonyl(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )acyloxy(C ₁ -C ₆ )aIkyl, aminocarbonyl(C ₁ -C ₆ )alkyl, (C ₁ -C ₈ )alkylaminocarbonyl(C ₁ -C ₅ )alkyl, di(C ₁ -C ₈ )alkylaminocarbonyl(C ₁ -C ₆ )alkyl (C ₁ -C ₈ )acylamino(C ₁ -C ₆ )alkyl, (C ₁ - C ₈ )alkoxycarbonylamino, (C ₁ -C ₈ )aIkoxycarbonylamino(C ₁ -C ₆ )alkyl, aminocarboxy(C ₁ -C(5)alkyl, (C ₁ - C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl and di(C ₁ -C ₈ )alkylaminocarboxy(C ₁ -C ₆ )alkyl, phenyl, napthyl, heteroaryl, bicyclic heteroaryl, phenoxy, naphthyloxy, heteroaryloxy, bicyclic heteroaryloxy, phenylthio, naphthylthio, heteroarylthio, bicyclic heteroarylthio, phenylsulfinyl, naphthylsulfinyl, heteroarylsulfinyl, bicyclic heteroarylsulfinyl, phenylsulfonyl, naphthylsulfonyl, heteroarylsulfonyl, bicyclic heteroarylsulfonyl, phenyl(C ₁ -C ₃ )alkyl, napthyl(C ₁ -C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, and bicyclic heteroaryl(C[-C ₃ )alkyl, wherein the aromatic and heteroaromatic groups are optionally and independently substituted with zero to three groups selected from: halogen, cyano, (C ₁ -C ₃ )alkyl, halo(C ₁ -C ₃ )alkyI, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ - C ₃ )alkanesulfonyl, and (C ₁ -C ₃ )alkoxycarbonyl. In a particular emodiment of the invention, W is a bond or an unsubstituted (C ₁ -C ₆ ) alkylene.

In a further particular embodiment, W is a bond or an unsubstituted (C ₁ -C ₃ ) alkylene. In another particular embodiment, W is a bond or an unsubstituted (C ₁ -C ₂ ) alkylene. W can likewise be embodied as a bond or a (Cj) alkylene.

E is a saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH ₂ ),, via bonds to two members of said ring, wherein said ring is composed of carbon atoms and zero to four hetero atoms selected from: zero to four nitrogen atoms, zero or one oxygen atoms, and zero or one sulfur atoms, said ring being optionally and independently substituted with zero to four groups selected from: halogen, hydroxy, (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl(C ₁ -C ₆ )alkyl, halo(C ₁ -

- 21 -

C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, and oxo groups, such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively, wherein n is 1 to 3. In a particular embodiment of this invention, E is a saturated 3-, 4-, 5-, 6-, or 7-membered ring or an unsaturated 5- or 6-membered ring composed of carbon atoms and 0-3 hetero atoms selected from 0, 1 , 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring atoms being substituted with the appropriate number of hydrogen atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, (C ₁ -C ₆ )alkyI, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ - C ₆ )alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively.

In another particular embodiment of this invention, E is a saturated 3-, A-, 5-, or 6- membered ring or an unsaturated 5- or 6-membered ring, wherein said ring is composed of carbon atoms, and 0-3 hetero atoms selected from 0, 1 , 2, or 3 nitrogen atoms, 0 or I oxygen atoms, and 0 or 1 sulfur atoms, said ring atoms being substituted with the appropriate number of hydrogen atoms, said ring being optionally substituted with up to four groups independently selected from fluorine, hydroxy, (C ₁ -C ₃ )alkyl, hydroxy(C ₁ -C ₃ )alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively. In another embodiment of this invention, E is a saturated 3-, 4-, 5-, or 6-membered ring or an unsaturated 5- or 6-membered ring composed of carbon atoms and 0 or 1 nitrogen atoms, said ring being optionally substituted with up to one hydroxy or hydroxy (C ₁ -C ₃ )alkyl group and with up to two (C ₁ -C ₃ ) alkyl groups. In specific embodiments of this invention, E is azetidine, pyrrolidine, hydroxypyrrolidine, (hydroxymethyl)pyrrolidine, methylpyrrolidine, piperidine, hydroxypiperidine, cyclopropane, methylcyclopropane, cyclopcntane, hydroxycyclopentane, cyclohexane, hydroxycyclohexane, or pyridine.

G is hydrogen, (C ₁ -C ₆ )alkyl, (C ₄ -C ₇ )heterocyclyl, hydroxy, hydroxy(C ₁ -C ₆ )alkyl, -NR ^4Q R ⁴ , -O(C ₁ -C ₃ )alkyl-NR ⁴⁰ R ⁴ , amino(C ₁ -C ₆ )alkylcarboxy, (C ₃ -C ₈ )cycloalkyl, (C ₁ -C ₆ )alkylamino(C ₁ - C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl, di(C ₁ -C ₆ )alkylamino, di(C ₁ -C ₆ )alkylamino(C ₁ -C ₆ )alkyl, CC=NH)NH ₂ , C(=NH)NHR ⁴ , NHC(=NH)NH ₂ , NHC(=NH)NHR ⁴ ; -(C ₀ -C ₆ )alkyl-NR ⁴ R ^4a , -NHC(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₆ )alkyl-NR ⁴ R ^4a , -C(=NH)NR ⁴ R ^4a , -C(=O)(C ₁ -C ₄ )alkylaryl, -C(=θχC ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl(C ₃ -C ₈ )cycloalkyI, or

-(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, wherein the (C ₁ -C ₄ )alkyl moiety is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino; and where R ^4a is H or (C ₁ -C ₃ )alkyl and R ⁴ is selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₆ )alkyl, and (C ₄ -C ₇ )heterocyclyl(C ₁ -C ₆ )alkyl, or R ⁴ and R ^4a , taken together with the nitrogen atom to which they are attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1 -3 heteroatoms selected from 1, 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally substituted with up to

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four groups independently selected from halogen, hydroxy, amino, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl,, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively; or an enantiomer, diastereomer or pharmaceutically acceptable salt thereof.

In one embodiment of the compounds of this invention, G is hydrogen, hydroxy, -O(C ₁ - C ₆ )alkyl-NR ^4a R ⁴ , (C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl-OH, -(C ₁ -C ₄ )alkyl-NRV ^a , -C(O)(C ₁ -C ₄ )alkyl-NRV ^a , -C(=O)(C ₁ -C ₄ )alkylaryl, amino, amino(C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )alkylamino(C ₁ -C ₆ )alkyl, -C(=O)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )hetcrocyclyl, -(C ₁ -C ₄ )alkyl(C ₃ -C ₇ )cycloalkyI, or -(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyI, wherein the (C ₁ -C ₄ )alkyl moiety of said

-C(=O)(C ₁ -C ₄ )alkylaryl, -C(0)(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl, -(C ₁ -C ₄ )alkyl(C ₃ -C ₇ )cycloalkyl and -(C ₁ -C ₄ )alkyl(C ₄ -C ₇ )heterocyclyl is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino, where R ⁴ is H or (C ₁ -C ₃ )alkyl and R ^4a is selected from H, (C ₁ -C ₃ )alkyl, heterocyclyl(C ₁ -C ₆ )alkyl, and (C ₄ -C ₇ )heterocyclyl(C ₁ -C ₆ )alkyl, or R ⁴ and R ^4a , taken together with the nitrogen atom to which they are attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1 -3 heteroatoms selected from 1 , 2, or 3 nitrogen atoms and 0 or 1 oxygen atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, amino, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )alkylamino, halo(C ₁ -C ₆ )alkyl, hydroxy(C ₁ -C ₆ )alkyl, amino(C ₁ -C ₆ )alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group. In another embodiment of this invention, at least one of R ⁴ and R ^4a is H.

In one embodiment of the compounds of this invention, G is hydrogen, -O(C ₁ -C _f i)alkyl- NR ^4a R ⁴ , (C ₄ -C ₆ )heterocyclyl, amino, amino(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkylamino(C ₁ - C ₃ )alkyl,-(C ₁ -C ₃ )alkyl-OH, -(C ₁ -C ₃ )alkyl-NRV ^a , -C(=O)(C ₁ -C ₃ )alkyl-ηR ⁴ R ⁴ °, -C(O)(C _r C ₃ )alkylphenyl, -C(O)(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl, -(C ₁ -C ₃ )alkyl(C ₃ -C ₆ )cycloalkyl, or -(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl, wherein the (C ₁ -C ₃ )alkyl moiety of said

-C(=O)(C ₁ -C ₃ )alkylphenyl, -C(=O)(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl, -(C ₁ -C ₃ )alkyl(C ₃ -C ₆ )cycloalkyl and -(C ₁ -C ₃ )alkyl(C ₄ -C ₆ )heterocyclyl is optionally substituted by amino, hydroxy, or (C ₁ -C ₃ )alkylamino, where R ⁴ is H or (C ₁ -C ₃ )alkyl and R ^4a is selected from H, (C ₁ -C ₃ )alkyl, (C ₃ -C ₆ )cycloalkyl(C ₁ -C ₃ )alkyl, and (C ₄ -C ₆ )heterocyclyl(C ₁ -C ₃ )alkyI.

In one embodiment of the compounds of this invention, G is hydrogen, -O(C ₁ -Cβ)alkyl- NR ^4a R ⁴ , (C ₅ -C ₆ )heterocyclyl, amino, (C ₁ -C ₂ )alkylamino, amino(C ₁ -C ₂ )alkyl, (C ₁ -C ₂ )alkylamino(C ₁ - C ₂ )alkyl,-(C ₁ -C ₂ )alkyl-OH, -C(O)(C ₁ -C ₂ )alkyl-NR ⁴ R ^4a , or -C(=O)(C ₁ -C ₂ )alkylphenyl, wherein the (C ₁ -C ₂ )alkyl moiety of said -Ct=O)(C ₁ -C ₂ )alkylphenyl is substituted by amino or (C ₁ -C ₂ )alkylamino, where R ⁴ is H or (C ₁ -C ₂ )alkyl and R ^4a is H. In more specific embodiments of this invention, G is -H, -OH, -CH ₂ OH, -NH ₂ , -NHCH ₃ , -CH ₂ NH ₂ , -CH ₂ NHCH ₃ , -CH ₃ , -CH ₂ CH ₂ OH, -CH ₂ CH ₂ NH ₂ , -CH ₂ NHCH ₂ CH ₃ , -CH ₂ NHCH(CH ₃ ) ₂ , -CH ₂ N(CH ₃ )-., -OCH ₂ CH ₂ NH ₂ , -C(O)CH ₂ N H ₂ , -CH ₂ NHCH ₂ (C ₆ H _{1 1} ), or (R)-C(O)CH(NH ₂ )CH ₂ (C ₆ Hs).

- 23 -

Particular embodiments of the invention are compounds of Formulae II, Ua, Hb, lie, 111, IIIa, HIb, IIIc, IV, lVa, IVb, and IVc:

or an enantiomer, diastereomer, or salt thereof.

- 24 -

wherein R, R ¹ , R ² , R ³ , Ring A, A ¹ , A ⁴ , Q, W, and G are as defined above for Formula I or an enantiomer, diastereomer or salt thereof. Specific and particular values for each variable in Formulae II, IIa, Hb, lie, III, IIIa, UIb, IIIc, IV, IVa, IVb, and IVc are as described for Formula I.

Other embodiments of the invention are compounds according to Formulae II, IIa, llb, Uc, III, UIa, 1Hb, IIIc, IV, IVa, IVb, and IVc wherein:

R is (a) (C ₁ -C ₈ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, (C ₃ -C ₇ )cycloalkyl, (C ₅ - C ₇ )cycloalkenyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₂ -C ₃ )alkenyl, (C ₃ - C ₇ )cycloalkyl(C ₂ -C ₃ )alkynyl, (C ₁ -C ₈ )-alkoxy, (C ₃ -C ₇ )cycloalkoxy, (C ₃ -C ₇ )cycloalkoxy(C ₁ -C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkoxy, (C ₁ -C ₈ )alkylthio, (C ₃ -C ₇ )cycloalkylthio, (C ₃ -C ₇ )cycloalkylthio(C ₁ - C ₃ )alkyl, (C ₃ -C ₇ )cycloalkyl(C ₁ -C ₃ )alkylthio, azepano, azetidino, piperidino, pyrrolidine or tri(C ₁ - Gi)alkylsilyl, each optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyI, (C ₃ -C<;)cycloalkyl, (C ₁ - C ₆ )alkoxy, (C[-C ₆ )cycloalkoxy, and oxo; (b) aryl, heteroaryl, aryloxy, heteroaryloxy, aryI(C ₁ - C ₃ )alkyl, heteroaryl(C ₁ -C ₃ )alkyl, aryl(CpC ₃ )alkoxy, heteroaryI(C ₁ -C ₃ )alkoxy, arylethenyl, heteroarylethenyl, or arylethynyl, heteroarylethynyl, each optionally substituted with up to three substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C ₁ - C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, halo(C ₁ -C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₅ )alkoxy, (C ₃ - C ₆ )cycloalkoxy, (C ₄ -C ₇ )cyclo-alkylalkoxy, halo(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ - C ₆ )alkylthiό, (C ₁ -C ₆ )alkanesulfinyl, halo(C ₁ -C ₆ )alkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, halo(C ₁ - C ₆ )alkanesulfonyl, H ₂ NCO, H ₂ NSO ₂ , (C ₁ -C ₆ )alkylaminocarbonyl, and (C ₁ -C ₆ )alkylaminosulfonyl.; or (c) a divalent radical selected from -(CH ₂ ),)- or -(CH ₂ )s-, which is attached to R ¹ to form a fused or spirofused ring system, and is optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, halo(C ₁ -C ₆ )alkyl _s (C ₁ - C ₆ )alkoxy and oxo. R ¹ is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-l ,3-dioxole, or (C ₃ -

C ₇ )cycloalkyl ring optionally substituted with up to four subslituents independently selected from the group consisting of fluorine, chlorine, bromine, cyano, (C ₁ -C ₆ )alkyl, (C ₃ -C ₆ )cycloalkyl, halo(C ₁ - C ₆ )alkyl, halo(C ₃ -C ₆ )cycloalkyl, (C ₁ -C ₆ )aIkoxy, (C ₃ -C ₆ )cycloalkoxy, (C ₄ -C ₇ )cycloalkylalkoxy, ha!o(C ₁ -C ₆ )alkoxy, (C ₁ -C ₆ )alkylthio, halo(C ₁ -C ₆ )alkyIthio, (C ₁ -C ₆ )alkanesulfιnyl, halo(C ₁ - C ₆ )alkanesulfinyl, (C ₁ -C ₆ )alkanesulfonyl, halo(C ₁ -C ₆ )alkanesulfonyl, H ₂ NSO ₂ , H ₂ NCO, (C ₁ - C ₃ )alkylaminosulfonyl, and (C ₁ -C ₃ )alkylaminocarbonyl;

R ² is a) -H;b) (C ₁ -C ₁₀ )alkyI, (C ₂ -C _l0 )alkenyl, (C ₂ -C ₁₀ )alkynyl, (C ₁ -C ₁₀ )alkoxy, (C ₁ - C ₁₀ )alkylthio, (C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )aIkyl, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )alkylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkylthio, (C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )alkylamino, (C ₁ -C ₃ )alkylthio(C ₁ -C ₃ )alkoxy, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₃ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylamino(C ₁ - C ₅ )alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkoxy(C ₁ -C ₃ )alkyl, aminocarbonylamino(C ₁ -C ₁₀ )alkyl, aminocarbonylamino(C _t -C ₁₀ )alkoxy, aminocarbonylamino-(C ₁ -

- 25 -

C ₁₀ )alkylthio, aminocarbonylamino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₃ )alkanoylamino(C ₁ -C ₅ )alkyl, (C ₁ - C ₅ )aIkanoylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkanoylamino(C ₁ -C ₃ )alkylthio, (C ₁ -C ₅ )- alkanoylamino(C ₁ -C ₅ )alkylamino, aminosulfonylamino(C ₁ -C ₁₀ )alkyl, aminosulfonylamino(C ₁ - C ₁₀ )alkoxy, aminosulfonylamino(C _| -C ₁₀ )alkylthio, aminosu]fonylamino(C ₁ -C ₁₀ )alkylamino, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₃ )alkyl, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkanesulfonylamino(C ₁ -C ₅ )alkylamtno, formylamino(C ₁ -C ₅ )alkyl, formylamino(C ₁ -C ₅ )alkoxy, formylamino(C ₁ -C ₅ )alkylthio, formylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkoxycarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxy- carbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₃ )alkoxycarbonylamino(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkoxy- carbonylamino(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )aIkylaminocarbonylamino(C ₁ -C ₅ )alkyl, (C ₁ -

C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkyIaminocarbonytamino(C ₁ -C ₅ )alkyIthio, (C ₁ - C ₅ )alkylaminocarbonylamino(C ₁ -C ₅ )alkylamino, aminocarbonyl(C ₁ -C ₅ )alkyl, aminocarbonyl(C ₁ - C ₅ )alkoxy, aminocarbonyl(C ₁ -C ₅ )alkylthio, aminocarbonyl(C ₁ -C ₅ )alkyIamino, (C ₁ - C ₅ )alkylaminocarbonyI(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarbonyl(C ₁ -C ₅ )alkyamino, aminocarboxy(C ₁ -C ₅ )alkyl, aminocarboxy(C ₁ -C ₅ )alkoxy, aminocarboxy(C ₁ -C ₅ )alkylthio, aminocarboxy(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkylamino- carboxy(C ₁ -C ₅ )aIkoxy, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkylaminocarboxy(C ₁ - C ₅ )alkylamino, (C ₁ -C ₁₀ )alkoxycarbonylamino, (C ₁ -C ₁₀ )alkylaminocarbonylamino, or (C ₁ -C ₁₀ )- alkanoylamino, each optionally substituted by (1) 1 to 5 fluorine atoms; and/or (2) 1 group selected from cyano, hydroxyl, (C ₁ -C ₃ )alkyl, (C ₁ -G,)alkoxy, (C ₃ -C ₄ )cycloalkyl, (C ₃ -C ₄ )cycloalkoxy, halo(C ₁ -C ₃ )aIkyl, halo(C ₁ -C ₃ )alkoxy, halo(C ₃ -C«,)cycloalkyl ₃ and halo(C ₃ -C ₄ )cycloalkoxy wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone.

R ³ is -H, halogen, (C ₁ -C ₃ )aIkyl, (C ₁ -C ₃ )alkoxy, hydroxyl, hydroxy(C ₁ -C ₃ )alkyl, hydroxy(C ₁ -C ₃ )alkoxy, (C ₁ -C ₄ )alkanoylamino, (C ₁ -C ₃ )alkoxycarbonylamino, (C ₁ -

C ₃ )alkylaminocarbonylamino, di(C ₁ -C ₃ )alkyIaminocarbonylamino, (C ₁ -C ₃ )alkanesulfonylamino, (C ₁ -QOalkylaminosulfonylamino, di(C ₁ -C ₃ )alkylaminosulfonylamino, phenylamino or heteroarylamino in which each phenylamino and heteroarylamino group is optionally substituted with 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, cyano, (C ₁ - C ₃ )alkyl, halo(C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, halo(C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )alkanesulfbnyl, and (C ₁ - C ₃ )alkoxycarbonyl; provided that (i) R ² and R ³ are not both hydrogen and (ii)when R ³ is hydroxyl, halogen, or optionally substituted phenylamino or heteroarylamino, R ² is not (C ₁ -C ₁₀ )alkoxy, (Cp C ₁₀ )alkylthio, (C-C^alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -C ₅ )alkyl, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkoxy, (C ₁ - C ₅ )alkoxy(C ₁ -C ₅ )alkylthio, (C ₁ -C ₅ )alkoxy(C ₁ -C ₅ )alkylamino, (C ₁ -C _J )alkylthio(C _l -C ₅ )alkoxy, (C ₁ - C ₅ )alkylthio(C ₁ -C ₅ )alkylamino, (C ₁ -C ₅ )alkylthio(C ₁ -Cj)alkylthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )alkylamino(C ₁ -C ₃ )alkyIthio, (C ₁ -C ₅ )alkylamino(C ₁ -C ₃ )alkylamino, aminocarbonylamino(C ₁ -C ₁₀ )aIkoxy, aminocarbonylamino(C ₁ -d^alkylthio, aminocarbonyl- amino(C ₁ -C ₁₀ )alkylamino, (C ₁ -C ₅ )alkanoyIamino(C ₁ -C ₅ )alkoxy, (C ₁ -C ₅ )aIkanoylamino(C ₁ -