Method of preventing or treating atherosclerosis or restenosis

A method of preventing or treating atherosclerosis or restenosis in a mammal, comprising administering to said mammal an effective amount of a compound selected from the group consisting of structures of Formula X, Formula XII, Formula XIII, Formula XIV and Formula XV,

• wherein Formula X is
• 34
• and pharmaceutically acceptable salts thereof;
• and
• wherein ring A is a saturated or unsaturated fused double or triple heterocyclic ring having 1, 2, 3 or 4 heteroatoms selected from group consisting of oxygen, sulfur, or nitrogen;
• and
• wherein R and Xx are the appropriated substitutents, respectively;
• wherein Formula XII is
• 35
• wherein,
• XXII is Cl, Br, F, CN or NO2;
• GXII is
• a) C1-7alkyl which partially unsaturated and is substituted by hydroxy, or
• b) C1-4alkyl substituted by NRXII-1RXII-2 or 4-tetrahydropyran;
• RXII-1 is C2-7alkyl substituted by hydroxy, C1-4alkoxy, arylXII, or heteroaryl;
• RXII-2 is hydrogen or C1-7alkyl;
• or
• RXII-1 and RXII-2 together with the nitrogen to which they are attached form morpholine which may be optionally substituted by XII-aryl or C1-7alkyl;
• WXII is a heterocycle of formula W1XII, W3XII, or W4XII;
• 36
• [It is intended that the R4 and R8 substituent and substituents A-F, J and K on the W1XII, W3XII, and W4XII Formulae above, as well as the W numbers under the formulas, be succeeded by the Roman Numeral XII.]
• AXII is CRXII-4 or nitrogen;
• BXII is CRXII-5 or nitrogen;
• CXII is CRXII-6 or nitrogen;
• EXII and FXII are such that
• a) one is oxygen and the other is C(═O);
• or
• b) EXII is C(═O) and FXII is NRXII-7;
• JXII and KXII are such that
• a) JXII is nitrogen and KXII is CRXII-8;
• or
• b) JXII is CRXII-6 and KXII is nitrogen;
• with the provisos that when WXII is of formula W3XII and
• JXII is nitrogen, then at least one of AXII and BXII is nitrogen;
• RXII-4 is H, halogen, or C1-4alkyl optionally substituted by one to three halogens;
• RXII-5 is
• a) H,
• b) halo,
• c) ORXII-12,
• d) SRXII-12,
• e) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXII-12, SRXII-12, NRXII-10RXII-11, or halo,
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXII-12, SRXII-12, or NRXII-10RXII-11,
• g) (C═O)RXII-9,
• h) S(O)mXIIRXII-9,
• i) (C═O)ORXII-2,
• j) NHSO2RXII-9,
• k) nitro, or
• l) cyano;
• RXII-6 is
• a) H,
• b) halo,
• c) arylXII,
• d) hetXII,
• e) ORXII-12,
• f) SRXII-2,
• g) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXII-12, SRXII-12, NRXII-10RXII-11, arylXII, halo, C3-8cycloalkyl optionally substituted by OR12, or hetXII, attached through a carbon atom,
• h) NRXII-10RXII-11,
• i) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXII-12, SRXII-12, or NRXII-10RXII-11,
• j) (C═O)RXII-9,
• k) S(O)mXIIRXII-9,
• l) (C═O)ORXII-2,
• m) NHSO2RXII-9,
• n) nitro, or
• o) cyano;
• RXII-7 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXII-12, SRXII-12, NRXII-10RXII-11, or halo,
• c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, XII-12 XII-12 or 10 XI1 ORXII-12, SRXII-12, or NRXII-10RXII-11,
• d) arylXII, or
• e) hetXII;
• RXII-8 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXII-12, SRXII-12, NRXII-10RXII-11, or halo,
• c) ORXII-12, or
• d) SRXII-12;
• RXII-9 is
• a) C1-7alkyl,
• b) NRXII-10RXII-11,
• c) arylXII, or
• d) hetXII, wherein said hetXII is bound through a carbon atom;
• RXII-10 and RXII-11 are independently
• a) H,
• b) arylXII,
• c) C1-7alkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from CONR2R2, CO2R2, hetXII, arylXII, cyano, or halo,
• d) C2-7alkyl which may be partially unsaturated and is substituted by one or more substituents selected from NRXII-2RXII-2, ORXII-2, or SRXII-2,
• e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXII-2, SRXII-2, or NRXII-2RXII-2, or
• f) RXII-10 and RXII-11 together with the nitrogen to which they are attached form a hetXII;
• RXII-12 is
• a) H,
• b) arylXII,
• c) hetXII,
• d) C1-7alkyl optionally substituted by arylXII, hetXII, or halogen,
• e) C2-7alkyl substituted by ORXII-2, SRXII-2, or NRXII-2RXII-2, or
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXII-2, SRXII-2, or NRXII-2RXII-2;
• each mXII is independently 1 or 2;
• arylXII is a phenyl radical or an ortho-fused bicyclic carbocyclic radical wherein at least one ring is aromatic, and arylXII maybe optionally substituted with one or more substituents selected from halo, OH, cyano, NRXII-2RXII-2, CO2RXII-2, CF3, C1-6alkoxy, and C1-6 alkyl which maybe further substituted by one to three SRXII-2, NRXII-2RXII-2, ORXII-2, or CO2RXII-2 groups;
• hetXII is a four- (4), five- (5), six- (6), or seven- (7) membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from oxygen, sulfur, or nitrogen, which is optionally fused to a benzene ring, or any bicyclic heterocycle group, and hetXII may be optionally substituted with one or more substituents selected from halo, OH, cyano, phenyl, CO2RXII-2, CF3, C1-6alkoxy, oxo, oxime, and C1-6 alkyl which may be further substituted by one to three SRXII-2, NRXII-2RXII-2, ORXII-2, or CO2RXII-2 groups;
• halo or halogen is F, Cl, Br, I;
• 1 represents the point of attachment between WXII and GXII;
• 2 represents the point of attachment between WXII and the carbonyl group of Formula (I);
• and a pharmaceutically acceptable salt thereof;
• wherein Formula XIII is
• 37
• wherein,
• XXIII is Cl, Br, F, CN or NO2;
• GXIII is
• a) C3-7alkyl which is partially unsaturated and is substituted by hydroxy, or
• b) C1-7alkyl substituted by NRXIII-1RXIII-2 or 4-tetrahydropyran;
• RXIII-1 is C2-7alkyl substituted by hydroxy, C1-4alkoxy, arylXII, or heteroarylXII;
• RXIII-2 is hydrogen or C1-7alkyl;
• or
• RXIII-1 and RXIII-2 together with the nitrogen to which they are attached form morpholine which may be optionally substituted by arylXII or C1-7alkyl;
• WXIII is
• 38
• BXIII is CRXIII-5, or nitrogen;
• CXIII is CRXIII-6 or nitrogen;
• with the provisos that BXIII and CXIII cannot be both nitrogen;
• RXIII-4 is H, halogen, or C1-4alkyl optionally substituted by one to three halogens;
• RXIII-5 is
• a) H,
• b) halo,
• c) ORXIII-12,
• d) SRXIII-12,
• e) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIII-12, SRXIII-12, NRXIII-10RXIII-11, or halo,
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIII-12, SRXIII-12, or NRXIII-10RXIII-11,
• g) (C═O)RXIII-9,
• h) S(O)mXIIIRXIII-9,
• i) (C═O)ORXIII-2,
• j) NHSO2RXIII-9,
• k) nitro, or
• l) cyano;
• RXIII-6 is
• a) H,
• b) halo,
• c) arylXIII,
• d) hetXIII, or
• e) RXIII-7;
• RXIII-7 is
• a) ORXIII-12,
• b) SRXIII-12,
• c) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIII-12, SRXIII-12, NRXIII-10RXIII-11, arylXIII, halo, C3-8cycloalkyl optionally substituted by ORXIII-12, or hetXIII attached through a carbon atom,
• d) NRXIII-10RXIII-11,
• e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIII-12, SRXIII-12, or NRXIII-10RXIII-11,
• f) (C═O)RXIII-9,
• g) S(O)mXIIIRXIII-9,
• h) (C═O)ORXIII-2,
• i) NHSO2RXIII-9,
• j) nitro, or
• k) cyano;
• RXIII-8 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIII-12, SRXIII-12, NRXIII-10RXIII-11, or halo,
• c) ORXIII-12, or
• d) SRXIII-12,
• RXII-9 is
• a) C1-7alkyl,
• b) NRXIII-10RXIII-11,
• c) arylXIII, or
• d) hetXIII, wherein said hetXIII is bound through a carbon atom;
• RXIII-10 and RXIII-11 are independently
• a) H,
• b) arylXIII,
• c) C1-7alkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from CONRXIII-2RXIII-2, CO2RXIII-2, hetXXIII, arylXIII, cyano, or halo,
• d) C2-7alkyl which may be partially unsaturated and is substituted by one or more substituents selected from NRXIII-2R2, ORXIII-2, or SRXIII-2,
• e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIII-2, SRXIII-2, or NRXIII-2RXIII-2, or
• f) RXIII-10 and RXIII-11 together with the nitrogen to which they are attached form a hetXIII;
• RXIII-12 is
• a) H,
• b) arylXIII,
• c) hetXIII,
• d) C1-7alkyl optionally substituted by arylXIII, hetXIII, or halogen,
• e) C2-7alkyl substituted by ORXIII-2, SRXIII-2, or NRXIII-2RXIII-2, or
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIII-2, SRXIII-2, or NRXIII-2RXII-2;
• each mXIII is independently 1 or 2;
• arylXIII is a phenyl radical or an ortho-fused bicyclic carbocyclic radical wherein at least one ring is aromatic, and arylXIII maybe optionally substituted with one or more substituents selected from halo, OH, cyano, NRXIII-2RXIII-2, CO2RXIII-2, CF3, C1-6alkoxy, and C1-6 alkyl which maybe further substituted by one to three SRXIII-2, NRXIII-2RXIII-2, ORXIII-2, or CO2RXIII-2 groups;
• hetXIII is a four- (4), five- (5), six- (6), or seven- (7) membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from oxygen, sulfur, or nitrogen, which is optionally fused to a benzene ring, or any bicyclic heterocycle group, and XIII-het may be optionally substituted with one or more substituents selected from halo, OH, cyano, phenyl, CO2RXIII-2, CF3, C1-6alkoxy, oxo, oxime, and C1-6 alkyl which may be further substituted by one to three SRXIII-2, NRXIII-2RXIII-2, ORXIII-2, or CO2RXIII-2 groups;
• halo or halogen is F, Cl, Br, I;
• 1 represents the point of attachment between WXIII and GXIII;
• 2 represents the point of attachment between W and the carbonyl group of Formula (I);
• and a pharmaceutically acceptable salt thereof;
• wherein Formula XIV is
• 39
• wherein,
• XXIV is Cl, Br, F, CN, or NO2;
• GXIV is
• a) C1-4alkyl which is fully saturated or partially unsaturated and is substituted by hydroxy, or
• b) C1-4alkyl substituted by NRXIV-1RXIV-2 or 4-tetrahydropyran;
• RXIV-1 is C2-7alkyl substituted by hydroxy, C1-4alkoxy, heteroaryl, or arylXIV;
• RXIV-2 is hydrogen or C1-7alkyl;
• or
• RXIV-1 and RXIV-2 together with the nitrogen to which they are attached form morpholine which may be optionally substituted by arylXIV or C1-7alkyl;
• or pyrrolidine substituted by hydroxy;
• WXIV is a heterocycle of formula W1XIV, W2XIV, W3XIV, W4XIV, W5XIV, W6XIV, W7XIV, W8XIV, W9XIV, W10XIV, W11XIV, W12XIV, W13XIV, W14XIV, W15XIV, W16XIV, W17XIV, W18XIV, W19XIV, W20XIV, W21XIV or W22XIV
• 40 41 42
• [It is intended that the R substituents and substituents A-F, J, K and Y on the W Formulae above, as well as the W number under the formulas, be succeeded by the Roman Numeral XIV.]
• AXIV is CRXIV4 or nitrogen;
• BXIV is CRXIV-5 or nitrogen;
• CXIV is CRXIV-6 or nitrogen;
• DXIV is CRXIV-8 or nitrogen;
• EXIV and F are such that one is oxygen and the other is C(═O);
• JXIV is NRXIV-7 or oxygen;
• KXIV and L are defined such that
• a) KXIV is CRXIV-5 and LXIV is CRXIV-6, or
• b) KXIV is absent and LXIV is sulfur;
• MXIV is oxygen, sulfur, or S(O)m;
• YXIV is oxygen or sulfur;
• RXIV-4 is H, halogen, or C1-4alkyl optionally substituted by one to three halogens;
• RXIV-5 is
• a) H,
• b) halo,
• c) ORXIV-12,
• d) SRXIV-12,
• e) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIV-12, SRXIV-12, NRXIV-10RXIV-11, or halo,
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIV-12, SRXIV-12, or NRXIV-10RXIV-11,
• g) (C═O)RXIV-9,
• h) S(O)mXIVRXIV-9,
• i) (C═O)ORXIV-2,
• j) NHSO2RXIV-9,
• k) nitro, or
• l) cyano;
• RXIV-6 is
• a) H,
• b) halo,
• c) arylXIV,
• d) hetXIV,
• e) ORXIV-12,
• f) SRXIV-12,
• g) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIV-12, SRXIV-12, NRXIV-10RXIV-11, XIV-aryl, halo, C3-8cycloalkyl optionally substituted by ORXIV-12, or XIV-het attached through a carbon atom,
• h) NRXIV-10RXIV-11,
• i) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIV-12, SRXIV-12, or NRXIV-10RXIV-11,
• j) (C═O)RXIV-9,
• k) S(O)mXIVRXIV-9,
• l) (C═O)ORXIV-2,
• m) NHSO2RXIV-9,
• n) nitro, or
• o) cyano;
• RXIV-7 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIV-12, SRXIV-12, NRXIV-10RXIV-11, or halo,
• c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIV-12, SRXIV-12, or NRXIV-10RXIV-11,
• d) arylXIV, or
• e) hetXIV;
• RXIV-8 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXIV-12, SRXIV-12, NRXIV-10RXIV-11, or halo,
• c) ORXIV-12, or
• d) SRXIV-12;
• RXIV-9 is
• a) C1-7alkyl,
• b) NRXIV-10RXIV-11,
• c) arylXIV, or
• d) hetXIV wherein said XIV-het is bound through a carbon atom;
• RXIV-10 and RXIV-11 are independently
• a) H,
• b) arylXIV,
• c) C1-7alkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from CONRXIV-2RXIV-2, CO2RXIV-2, hetXIV, arylXIV, cyano, or halo,
• d) C2-7alkyl which may be partially unsaturated and is substituted by one or more substituents selected from NRXIV-2RXIV-2, ORXIV-2, or SRXIV-2,
• e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIV-2, SRXIV-2, or NRXIV-2RXIV-2, or
• f) RXIV-10 and RXIV-11 together with the nitrogen to which they are attached form a hetXIV;
• RXIV-12 is
• a) H,
• b) arylXIV,
• c) hetXIV
• d) C1-7alkyl optionally substituted by arylXIV, or halogen,
• e) C2-7alkyl substituted by ORXIv-2, SRXIV-2, or NRXIV-2RXIV-2, or
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXIV-2, SRXIV-2, or NRXIV-2RXIV-2;
• each mXIV is independently 1 or 2;
• arylXIV is a phenyl radical or an ortho-fused bicyclic carbocyclic radical wherein at least one ring is aromatic, and arylXIV may be optionally substituted with one or more substituents selected from halo, OH, cyano, NRXIV-2RXIV-2, CO2RXIV-2, CF3, C1-6alkoxy, and C1-6 alkyl which maybe further substituted by one to three SR2, NRXIV-2RXIV-2, ORXIV-2, or CO2RXIV-2 groups;
• hetXIV is a four- (4), five- (5), six- (6), or seven- (7) membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from oxygen, sulfur, or nitrogen, which is optionally fused to a benzene ring, or any bicyclic heterocycle group, and hetXIV may be optionally substituted with one or more substituents selected from halo, OH, cyano, phenyl, CO2RXIV-2, CF3, C1-6alkoxy, oxo, oxime, and C1-6 alkyl which may be further substituted by one to three SRXIV-2, NRXIV-2RXIV-2, ORXIV-2, or CO2RXIV-2 groups;
• halo or halogen is F, Cl, Br, I;
• 1 represents the point of attachment between W and G;
• 2 represents the point of attachment between W and the carbonyl group of Formula (I);
• and a pharmaceutically acceptable salt thereof;
• wherein Formula XV is
• 43
• or a pharmaceutically acceptable salt thereof,
• wherein,
• XXV is Cl, Br, F, CN or NO2;
• GXV is
• a) C1-4alkyl which is fully saturated or partially unsaturated and is substituted by hydroxy, or
• b) C1-4alkyl substituted by NRXV-1RXV-2 or 4-tetrahydropyran;
• RXV-1 is C2-7alkyl substituted by hydroxy, C1-4alkoxy, or aryl;
• RXV-2 is hydrogen or C1-7alkyl;
• or
• RXV-1 and RXV-2 together with the nitrogen to which they are attached form
• a) a morpholine which may be optionally substituted by aryl or C1-7alkyl;
• or
• b) a pyrrolidine ring substituted by hydroxy;
• WXV is a heterocycle of formula W1XV, W2XV, W3XV, W4XV, W5XV, W6XV, W7XV or W8XV
• 44 45
• [It is intended that the R substituents and substituents A, B, D, E, J, K and L on the WXV-1 to WXV-8 Formulae above, as well as the W number under the formulas, be succeeded by the Roman Numeral XV.]
• AXV is CRXV-4 or nitrogen;
• BXV is CRXV-5 or nitrogen;
• DXV is
• a) —(CR13RXV-14)aXV, where aXV is 2 or 3
• b) —(CR15RXV-16)4—,
• c) —YXV—CR13RXV-14—CR13RXV-14—,
• d) —CR13RXV-14—YXV—CR13RXV-14—,
• e) —YXV—CR13RXV-14—YXV—,
• f) —CR13RXV-14—CR13RXV-14—YXV—,
• g) —YXV—(CR13RXV-16)nXV—,
• h) —YXV—CR15═CR15—,
• i) —CR15═CR15—YXV—,
• k) —N═CR15—YXV—,
• l) —(CR15RXV-16)bXV—N═CR15—, where bXV is 0 or 1
• m) —CR15═N—(CR15RXV-16)bXV—, where bXV is 0 or 1
• n) —N═N—,
• o) —N═CR15—(CR15R16)bXV—, where bXV is 0 or 1
• p) —CR15═CR15—,
• q) —N═N—YXV,
• r) —YXVN═N—,
• s) —YXV—N═CR15, or
• t) —CR15RXV-16—YXV—CR15RXV-16—CR15RXV-16—;
• EXV is CR8 or nitrogen;
• JXV is CR15 or nitrogen;
• KXV is
• a) —(CR15RXV-16)aXV—, where aXV is 2 or 3, or
• b) —CR15═CR15—;
• LXV is
• a) —(CR15RXV-16)aXV—, where aXV is 2 or 3, or
• b) —YXV—(CR15RXV-16)—(CR15RXV-16)—;
• YXV is oxygen, S(O)mXV, or NRXV-7;
• with the provisos that:
• when WXV is of formula WXV1;
• GXV is C1-4alkyl which is fully saturated and is substituted by hydroxy or morpholinyl, in which morpholinyl is attached through nitrogen;
• AXV is CRXV-4;
• BXV is CRXV-5;
• and
• RXV-8 is hydrogen then at least one of RXV-13, RXV-14, or RXV-7 is not hydrogen or C1-7alkyl;
• when WXV is of formula WXV1, AXV is CRXV-4, BXV is CRXV-5, DXV is —YXV—CR13RXV-14—CR13RXV-14—, and RXV-8 is hydrogen then yXV is not oxygen;
• when WXV is of formula WXV1, AXV is CRXV-14, and BXV is CRXV-5 then DXV is not —CR15═CR15—;
• RXV-4 is H, halogen, or C1-4alkyl optionally substituted by one to three halogens;
• RXV-5 is
• a) H,
• b) halo,
• c) ORXV-12,
• d) SRXV-12,
• e) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXV-12, SRXV-12, NRXV-10RXV-11, or halo,
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXV-12, SRXV-12, or NRXV-10RXV-12,
• g) (C═O)RXV-9,
• h) S(O)mXVRXV-9,
• i) (C═O)ORXV-2,
• j) NHSO2RXV-9,
• k) nitro, or
• l) cyano;
• RXV-7 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXV-12, SRXV-12, NRXV-10RXV-11, or halo,
• c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXV-12, SRXV-12, or NRXV-10RXV-11,
• d) arylXV,
• e) hetXV,
• f) (C═O)RXV-9, or
• g) S(O)mXVRXV-9;
• RXV-8 is
• a) H,
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from ORXV-12, SRXV-12, NRXV-10RXV-11, or halo,
• c) ORXV-12, or
• d) SRXV-12;
• RXV-9 is
• a) C1-7alkyl optionally substituted by ORXV-12 or NRXV-2RXV-2,
• b) C3-8cycloalkyl optionally substituted by ORXV-12 or NRXV-2RXV-2,
• c) NRXV-10RXV-11,
• d) arylXV, or
• e) hetXV, wherein said hetXV is bound through a carbon atom;
• RXV-10 and RXV-11 are independently
• a) H,
• b) arylXV,
• c) C1-7alkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from CONR2RXV-2, CO2RXV-2, hetXV, arylXV, cyano, or halo,
• d) C2-7alkyl which may be partially unsaturated and is substituted by one or more substituents selected from NRXV-2RXV-2, ORXV-2, or SRXV-2,
• e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXV-2, SRXV-2, or NRXV-2RXV-2, or
• f) RXV-10 and RXV-11 together with the nitrogen to which they are attached form a hetXV;
• RXV-12 is
• a) H,
• b) arylXV,
• c) hetXV,
• d) C1-7alkyl optionally substituted by arylXV, or halogen,
• e) C2-7alkyl substituted by ORXV-2, SRXV-2, or NRXV-2RXV-2, or
• f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXV-2, SRXV-2, or NRXV-2RXV-2;
• RXV-13, RXV-14, RXV-15, and RXV-16 are independently
• a) H
• b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more ORXV-12, SRXV-12, NRXV-10RXV-11, or halo groups,
• c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, ORXV-12, SRXV-12, or NRXV-10RXV-11,
• d) arylXV,
• e) hetXV, wherein said hetXV is bound through a carbon atom,
• f) ORXV-12,
• g) SRXV-12,
• h) NRXV-10RXV-11;
• i) (C═O)ORXV-2, or
• j) R13 and R14 or R15 and R16 together with the carbon to which they are attached form (C═O);
• each mXV is independently 0, 1 or 2;
• each nXV is independently 1 or 3;
• arylXV is a phenyl radical or an ortho-fused bicyclic carbocyclic radical wherein at least one ring is aromatic, and arylXV may be optionally substituted with one or more substituents selected from halo, OH, cyano, NRXV-2RXV-2, CO2RXV-2, CF3, C1-6alkoxy, and C1-6 alkyl which maybe further substituted by one to three SRXV-2, NRXV-2RXV-2, ORXV-2, or CO2RXV-2 groups;
• hetXV is a four- (4), five- (5), six- (6), or seven- (7) membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from oxygen, sulfur, or nitrogen, which is optionally fused to a benzene ring, or any bicyclic heterocycle group, and XVhet may be optionally substituted with one or more substituents selected from halo, OH, cyano, phenyl, CO2RXV-2, CF3, C1-6alkoxy, oxo, oxime, and C1-6 alkyl which may be further substituted by one to three SRXV-2, NRXV-2RXV-2, ORXV-2, or CO2RXV-2 groups;
• halo or halogen is F, Cl, Br, I;
• 1 represents the point of attachment between WXV and GXV;
• 2 represents the point of attachment between WXV and the carbonyl group of Formula (I);
• and pharmaceutically acceptable salts thereof.