Urotensin II receptor antagonists

A compound of Formula (I):

• wherein:
• A is a-1, wherein, the lower portion of A is attached, relative to the nitrogen atom of Formula (I), to the 3 or 4 position on the benzene ring portion of Formula (I);
• wherein, when A is present, then G is hydrogen, or one substituent selected from C1-8alkyl, C2-8alkenyl, C3-14cycloalkyl or a —C[(R1)(R11)]-L-D moiety:
• or two C1-4alkyl substituents both attached to the common ring nitrogen atom of Formula (I), thus forming a quaternary ammonium salt;
• R1 is selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, and C2-8alkynyl;
• R11 is selected from the group consisting of hydrogen, C1-8alkyl and cyclopropyl;
• L is absent or C1-4alkyl;
• D is aryl, C3-14cycloalkyl, C5-14cycloalkenyl, heterocyclyl, or heteroaryl, wherein aryl and heteroaryl are optionally substituted with one, two, three or four substitutents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, C2-8alkenyl, C2-3alkenyloxy, hydroxy, C1-3alkylthio, fluoro, chloro, cyano, C1-3alkylcarbonyl, (C1-3alkylcarbonyl)amino, (C1-3alkyl)amino, di(C1-3alkyl)amino and C3-14cycloalkyl, wherein C3-14cycloalkyl is optionally substituted with one, two, three or four C1-3alkyl substituents;
• L2 is —C(R2)(R5)—(CR6R7)r—, wherein r is 0, 1 or 2;
• and wherein R5, R6, and R7 are independently hydrogen or C1-3alkyl;
• R2 is selected from the group consisting of heteroaryl, phenyl, heterocyclyl and C1-6alkyl, wherein phenyl is optionally substituted with [(R200—C1-6alkyl)(R1)]amino, [(R200-sulfonyl)(Ra)]amino or [(hydroxysulfonyl)(Ra)]amino, wherein heterocyclyl is optionally substituted with C1-4alkyl, aryl, heteroaryl, R200—C1-6alkyl or R200-sulfonyl, and
• wherein C1-6alkyl is optionally substituted with carboxy, hydroxy, R200, NRaRb, C1-6alkoxy, R200—C1-6alkoxy, R200-oxy, R200-thio, aminocarbonyl, carboxy-C1-6alkoxy, aminocarbonyl-C1-6alkoxy, (C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, [(R200—C1-6alkyl)(Ra)]amino, (R200—C1-6alkyl)-2-amino, (C1-6alkylcarbonyl)amino, (trihalo-C1-4alkylcarbonyl)amino, (R200—C1-6alkylcarbonyl)amino, (C1-6alkoxycarbonyl)amino, (R200—C1-6alkoxycarbonyl)amino, (C1-6alkoxy-C1-6alkylcarbonyl)amino, (R200-carbonyl)amino, (amino-C1-6alkylcarbonyl)amino, [(C1-6alkyl)amino-C1-6alkylcarbonyl]amino, [di(C1-6alkyl)amino-C1-6alkylcarbonyl]amino, (C1-6alkylcarbonyl-acetonitrile-carbonyl)amino, ureido, thioureido, acetamidino, guanidino, ({[(R200)(Ra)]aminocarbonyl}(Ra))amino, [(R200-oxycarbonyl)(Ra)]amino, [(R200)(Ra)]aminocarbonyloxy, aminosulfonyl, C1-6alkylsulfonyl, hydroxysulfonyl, (C1-6alkylsulfonyl)amino, (R200—C1-6alkylsulfonyl)amino, (R200—C2-6alkenylsulfonyl)amino, (C1-6alkylsulfonyl-C1-6alkylsulfonyl)amino, R200-sulfonyloxy, aminosulfonyloxy, (C1-6alkyl)aminosulfonyloxy, di(C1-6alkyl)aminosulfonyloxy, [(aminosulfonyl)(Ra)]amino, {[(C1-6alkyl)aminosulfonyl](Ra)}amino, {[di(C1-6alkyl)aminosulfonyl](Ra)}amino, [(hydroxysulfonyl)(Ra)]amino, [(R200-oxysulfonyl)(Ra)]amino, [(R200-sulfonyl)(Ra)]amino, [(R200)(Ra)]aminosulfonyloxy, or ({[(R200)(Ra)]aminosulfonyl}(Rc))amino;
• Ra is selected from the group consisting of hydrogen, C1-6alkyl, C1-6alkylcarbonyl and C3-8cycloalkyl;
• Rb is selected from the group consisting of hydrogen, C1-6alkyl or R201,
• R200 is C6-10aryl, heteroaryl, C3-8cycloalkyl or heterocyclyl each optionally substituted with one, two or three substituents independently selected from the group consisting of C1-4alkyl, trihalo-C1-4alkyl, C1-4alkoxy, trihalo-C1-4alkoxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, amino, C1-6alkyl-amino, diC1-6alkyl-amino, (C1-6alkylcarbonyl)amino, C1-6alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, chloro, fluoro, bromo and R202,
• wherein C3-8cycloalkyl or heterocyclyl is optionally substituted with one, two or three oxo substituents on available carbon atom ring members, and
• wherein heteroaryl having a nitrogen atom ring member is optionally substituted on the ring nitrogen atom with an oxy substituent and thus forms an oxide;
• R201 is C6-10aryl, heteroaryl, C3-8cycloalkyl or heterocyclyl,
• wherein aryl, heteroaryl, C3-8cycloalkyl or heterocyclyl are each optionally substituted with one, two or three substituents independently selected from the group consisting of C1-4alkyl, trihalo-C1-4alkyl, C1-4alkoxy, trihalo-C1-4alkoxy, amino, C1-6alkyl-amino, diC1-6alkyl-amino, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, (C1-6alkylcarbonyl)amino, C1-6alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, chloro, fluoro, bromo, aryl, heteroaryl, aryl-C1-6alkyl, aryl-sulfonyl and heteroaryl-sulfonyl,
• wherein C3-8cycloalkyl or heterocyclyl is optionally substituted with one, two or three oxo substituents on available carbon atom ring members, and
• wherein heteroaryl having a nitrogen atom ring member is optionally substituted on the ring nitrogen atom with an oxy substituent and thus forms an oxide;
• R202 is aryl, heteroaryl, aryl-C1-6alkyl, [(aryl-C1-6alkyl)(Ra)]amino, hydroxysulfonyl, aryl-sulfonyl, heteroaryl-sulfonyl or [(heteroaryl-sulfonyl)(Ra)]amino, wherein each aryl and heteroaryl are optionally substituted with one, two or three C1-4alkyl substituents;
• B is C6-10aryl, tetralinyl, indanyl, or a heteroaryl selected from the group consisting of pyridin-2-yl, pyridin-4-yl, pyrazol-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, imidazol-1-yl, thien-2-yl, isoquinolinyl, indolyl, quinolinyl, and thiazol-5-yl,
• wherein B is optionally substituted with one, two or three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, fluorinated (C1-4)alkoxy, halogen, cyano, hydroxy, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aminosulfonyl, (C1-4)alkylaminosulfonyl, di(C1-4)alkylaminosulfonyl, hydroxysulfonyl, aminosulfonylamino, (C1-4)alkylaminosulfonylamino, di(C1-4)alkylaminosulfonylamino, aminosulfonyloxy, (C1-4)alkylaminosulfonyloxy, and di(C1-4)alkylaminosulfonyloxy,
• provided that when B is selected from the group consisting of C6-10aryl, tetralinyl, indanyl, thien-2-yl, and indolyl, then B is independently substituted with two to three substitutents selected from the group consisting of C1-3alkoxy and hydroxy,
• provided that, when B is phenyl substituted at the 3,4-, 3,5- or 4,5-positions with an unbranched C1-3alkoxy substituent at each position, then phenyl may be further optionally substituted at a remaining open 3-, 4-, or 5-position with an additional C1-3alkoxy or hydroxy substituent;
• E is hydrogen, halogen, cyano, C1-3alkyl, C1-3alkoxy, C2-5alkenyl, amino, (C1-3alkyl)amino or di(C1-3alkyl)amino;
• X is O or S;
• and enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts thereof.