Ophthalmic compositions for treating ocular hypertension

A compound which is selected from Tables 1 through 4:

• TABLE 1
• Wherein R represents:
• n is 0 to 3;
• X, Y and Z, independently represent hydrogen or C1-6 alkyl;
• and Rc represents hydrogen, halogen, C1-6 alkyl, CF3, OCF3, N(CH3)3,
• COC1-6 alkyl, or methoxy;
• TABLE 2
• wherein R represents:
• n is 0 to 3;
• s is 1-5 ;
• X represents hydrogen or C1-6 alkyl;
• Rb and Ra
• independently represent hydrogen, methoxy, CO2X, NHAc, or C1-6 alkyl;
• Rc represents hydrogen, halogen, C1-6 alkyl, CF3, OCF3, N(CH3)2,
• COC1-6 alkyl, or methoxy
• TABLE 3
• wherein R represents:
• n is 0 to 3;
• s is 1-5;
• X represents hydrogen or C1-6 alkyl;
• and Rc represents
• hydrogen, halogen, C1-6 alkyl, CF3, OCF3, N(CH3)2, COC1-6 alkyl, or
• methoxy
• TABLE 4
• or
• wherein:
• Rb and Ra independently represent hydrogen, methoxy, CO2X, NHAc, or
• C1-6 alkyl;
• Rd represents C1-6 alkyl, pyridinyl, —O-phenyl, phenyl, thienyl, said
• pyridinyl and phenyl optionally substituted with 1-3 halogen, CF3, OCF3,
• N(CH3)2, methoxy or C1-6 alkyl;
• and
• Re represents methoxy, O(CH2)2N(CH3)2, or OH;
• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture
• thereof.

A method for treating ocular hypertension or glaucoma comprising administration to a patient in need of such treatment a therapeutically effective amount of a compound of structural formula I:

• or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
• wherein,
• R represents hydrogen, or C1-6 alkyl;
• R1 represents hydrogen or C1-6 alkyl, CF3, C1-6 alkoxy, OH, CORc, CO2R8, CONHCH2CO2R, N(R)2, said alkyl and alkoxy optionally substituted with 1-3 groups selected from Rb;
• X represents —(CHR7)p—;
• Y is not present, —CO(CH2)n—, or —CH(OR)—;
• Q represents N, CRy, or O, wherein R2 is absent when Q is O;
• Ry represents H, or C1-6 alkyl;
• Rw represents H, C1-6 alkyl, —C(O)C1-6 alkyl, —C(O)OC1-6 alkyl, —SO2N(R)2, —SO2C1-6 alkyl, —SO2C6-10 aryl, NO2, CN or —C(O)N(R)2;
• R2 represents hydrogen, C1-10 alkyl, C1-6 alkylSR, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —N(R)2, —COOR, or —(CH2)nC6-10 aryl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
• R3 represents hydrogen, C1-10 alkyl, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —(CH2)nCOOR, —(CH2)nC6-10 aryl, —(CH2)nNHR8, —(CH2)nN(R)2, —(CH2)nN(R8)2, —(CH2)nNHCOOR, —(CH2)nN(R8)CO2R, —(CH2)nN(R8)COR, —(CH2)nNHCOR, —(CH2)nCONH(R8), aryl, —(CH2)nC1-6—OR, CF3, —(CH2)nSO2R, —(CH2)nSO2N(R)2, —(CH2)nCON(R)2, —(CH2)nCONHC(R)3, —(CH2)nCONHC(R)2CO2R, —(CH2)nCOR8, nitro, cyano or halogen, said alkyl, alkoxy, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups of Ra;
• or, when Q is N, R2 and R3 taken together with the intervening N atom form a 4-10 membered heterocyclic carbon ring optionally interrupted by 1-2 atoms of O, S, C(O) or NR, and optionally having 1-4 double bonds, and optionally substituted by 1-3 groups selected from Ra;
• R4 and R5 independently represent hydrogen, C1-6 alkoxy, OH, C1-6 alkyl, COOR, SO3H, C1-6 alkylcarbonyl, S(O)qRy, —O(CH2)nN(R)2, —O(CH2)nCO2R, —OPO(OH)2, CF3, —N(R)2, nitro, cyano, C1-6 alkylamino, or halogen;
• R6 represents hydrogen, C1-10 alkyl, —(CH2)nC6-10 aryl, —NH(CH2)nC6-10 aryl, —(CH2)nC5-10 heteroaryl, —NH(CH2)nC5-10 heteroaryl, (C6-10 aryl)O—, —(CH2)nC3-10 heterocyclyl, —(CH2)nC3-8 cycloalkyl, —COOR, —C(O)CO2R, said aryl, heteroaryl, heterocyclyl and alkyl optionally substituted with 1-3 groups selected from Ra;
• R7 represents hydrogen, C1-6 alkyl, —(CH2)nCOOR or —(CH2)nN(R)2,
• R8 represents —(CH2)nC3-8 cycloalkyl, —(CH2)n 3-10 heterocyclyl, C1-6 alkoxy or —(CH2)nC5-10 heteroaryl, —(CH2)nC6-10 aryl said heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
• Ra represents F, Cl, Br, I, CF3, N(R)2, NO2, CN, —(CH2)nCOR8, —(CH2)nCONHR8, —(CH2)nCON(R8)2, —O(CH2)nCOOR, —NH(CH2)nOR, —COOR, —OCF3, —NHCOR, —SO2R, —SO2NR2, —SR, (C1-C6 alkyl)O—, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, (aryl)O—, —OH, (C1-C6 alkyl)S(O)m—, H2N—C(NH)—, (C1-C6 alkyl)C(O)—, (C1-C6 alkyl)OC(O)NH—, —(C1-C6 alkyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)-C3-10 heterocyclyl-Rw, —(CH2)n—Z1—C(═Z2)N(R)2, —(C2-6 alkenyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-C3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-Z1—C(═Z2)N(R)2, —(CH2)nSO2R, —(CH2)nSO3H, —(CH2)nPO(OR)2, cyclohexyl, morpholinyl, piperidyl, pyrrolidinyl, thiophenyl, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl, C2-6 alkenyl, and C1-C10 alkyl, said alkyl, alkenyl, alkoxy, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, and isothiazolyl optionally substituted with 1-3 groups selected from C1-C6 alkyl, and COOR;
• Z1 and Z2 independently represents NRw, O, CH2, or S;
• Rb represents C1-6 alkyl, —COOR, —SO3R, —OPO(OH)2, —(CH2)nC6-10 aryl, or —(CH2)nC5-10 heteroaryl;
• Rc represents hydrogen, C1-6 alkyl, or —(CH2)nC6-10 aryl;
• m is 0-3;
• n is 0-3;
• q is 0-2;
• and
• p is 0-1.