Patent ID: 6482825
Filing Date: 2002-11-19
Classification: A61K,A61P,C07D,C07K

Abstract:
A compound of the formula the racemic-diastereomeric mixture or optical isomer of said compound or the pharmaceutically-acceptable salt thereof,wherein e is 1; n is 1; w is 1; Y is oxygen or sulfur; R1 is hydrogen, â€”CN, â€”(CH2)qN(X6)C(O)X6, â€”(CH2)qN(X6)C(O)(CH2)tâ€”A1, â€”(CH2)qN(X6)SO2(CH2)tâ€”A1, â€”(CH2)qN(X6)SO2X6, â€”(CH2)qN(X6)C(O)N(X6)(CH2)tâ€”A1, â€”(CH2)qN(X6)C(O)N(X6)(X6), â€”(CH2)qC(O)N(X6)(X6), â€”(CH2)qC(O)N(X6)(CH2)tâ€”A1, â€”(CH2)qC(O)OX6, â€”(CH2)qC(O)O(CH2)tâ€”A1, â€”(CH2)qOX6, â€”(CH2)qOC(O)X6, â€”(CH2)qOC(O)(CH2)tâ€”A1, â€”(CH2)qOC(O)N(X6)(CH2)tâ€”A1, â€”(CH2)qOC(O)N(X6)(X6), â€”(CH2)qC(O)X6, â€”(CH2)qC(O)(CH2)tâ€”A1, â€”(CH2)qN(X6)C(O)OX6, â€”(CH2)qN(X6)SO2N(X6)(X6), â€”(CH2)qS(O)mX6, â€”(CH2)qS(O)m(CH2)tâ€”â€”A1, â€”C1-C10)alkyl, â€”(CH2)tâ€”A1, â€”(CH2)qâ€”(C3-C7)cycloalkyl, â€”(CH2)qâ€”Y1â€”(C1-C6)alkyl, â€”(CH2)qâ€”Y1â€”(CH2)tâ€”A1 or â€”(CH2)qâ€”Y1â€”(CH2)tâ€”(C3-C7)cycloalkyl; where the alkyl and cycloalkyl groups in the definition of R1 are optionally substituted with (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy, carboxyl, â€”CONH2, â€”S(O)m(C1-C6)alkyl, â€”CO2(C1-C4)alkyl ester, 1H-tetrazol-5-yl or 1, 2 or 3 fluoro; Y1 is O, S(O)m, â€”C(O)NX6â€”, â€”CH&boxH;CHâ€”, â€”Câ‰¡Câ€”, â€”N(X6)C(O)â€”, â€”C(O)NX6â€”, â€”C(O)Oâ€”, â€”OC(O)N(X6)â€” or â€”OC(O)â€”; q is 0, 1, 2, 3 or 4; t is 0, 1, 2 or 3; said (CH2)q group and (CH2)t group may each be optionally substituted with hydroxyl, (C1-C4)alkoxy, carboxyl, â€”CONH2, â€”S(O)m(C1-C6)alkyl, â€”CO2(C1-C4)alkyl ester, 1H-tetrazol-5-yl, 1, 2 or 3 fluoro, or 1 or 2 (C1-C4)alkyl; R2 is hydrogen, (C1-C8)alkyl, â€”(C0-C3)alkyl-(C3-C8)cycloalkyl, â€”(C1-C4)alkyl-A1 or A1; where the alkyl groups and the cycloalkyl groups in the definition of R2 are optionally substituted with hydroxyl, â€”C(O)OX6, â€”C(O)N(X6)(X6), â€”N(X6)(X6), â€”S(O)m(C1-C6)alkyl, â€”C(O)A1, â€”C(O)(X6), CF3, CN or 1, 2 or 3 halogen; R3 is A1, (C1-C10)alkyl, â€”(C1-C6)alkyl-A1, â€”(C1-C6)alkyl-(C3-C7)cycloalkyl, â€”(C1-C5)alkyl-X1â€”(C1-C5)alkyl, â€”(C1-C5)alkyl-X1â€”(C0-C5)alkyl-A1 or â€”(C1-C5)alkyl-X1â€”(C1-C5)alkyl-(C3-C7)cycloalkyl; where the alkyl groups in the definition of R3 are optionally substituted with â€”S(O)m(C1-C6)alkyl, â€”C(O)OX3, 1, 2, 3, 4 or 5 halogens, or 1, 2 or 3 OX3; X1 is O, S(O)m, â€”N(X2)C(O)â€”, â€”C(O)N(X2)â€”, â€”OC(O)â€”, â€”C(O)Oâ€”, â€”CX2&boxH;CX2â€”, â€”N(X2)C(O)Oâ€”, â€”OC(O)N(X2)â€” or â€”Câ‰¡Câ€”; X4 is hydrogen or (C1-C6)alkyl R6 is a bond or is where a and b are independently 0, 1, 2 or 3; X5 and X5a are each independently selected from the group consisting of hydrogen, trifluoromethyl, A1 and optionally substituted (C1-C6)alkyl; the optionally substituted (C1-C6)alkyl in the definition of X5 and X5a is optionally substituted with a substituent selected from the group consisting of A1, OX2, â€”S(O)m(C1-C6)alkyl, â€”C(O)OX2, (C3-C7)cycloalkyl, â€”N(X2)(X2) and â€”C(O)N(X2)(X2); Z1 is a bond, O or Nâ€”X2, provided that when a and b are both 0 then Z1 is not Nâ€”X2 or O; R7 and R8 are independently hydrogen or optionally substituted (C1-C6)alkyl; where the optionally substituted (C1-C6)alkyl in the definition of R7 and R8 is optionally independently substituted with A1, â€”C(O)Oâ€”(C1-C6)alkyl, â€”S(O)m(C1-C6)alkyl, 1 to 5 halogens, 1 to 3 hydroxy, 1 to 3 â€”Oâ€”C(O)(C1-C10)alkyl or 1 to 3 (C1-C6)alkoxy; or R7 and R8 can be taken together to form â€”(CH2)râ€”Lâ€”(CH2)râ€”; where L is C(X2)(X2), S(O)m or N(X2); A1 for each occurrence is independently (C5-C7)cycloalkenyl, phenyl or a partially saturated, fully saturated or fully unsaturated 4- to 8-membered ring optionally having 1 to 4 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, a bicyclic ring system consisting of a partially saturated, fully unsaturated or fully saturated 5- or 6-membered ring, optionally having 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen, fused to a partially saturated, fully saturated or fully unsaturated 5- or 6-membered ring, optionally having 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur and oxygen; A1 for each occurrence is independently optionally substituted, in one or optionally both rings if A1 is a bicyclic ring system, with up to three substituents, each substituent independently selected from the group consisting of F, Cl, Br, I, OCF3, OCF2H, CF3, CH3, OCH3, â€”OX6, â€”C(O)N(X6)(X6), â€”C(O)OX6, oxo, (C1-C6)alkyl, nitro, cyano, benzyl, â€”S(O)m(C1-C6)alkyl, 1H-tetrazol-5-yl, phenyl, phenoxy, phenylalkyloxy, halophenyl, methylenedioxy, â€”N(X6)(X6), â€”N(X6)C(O)(X6), â€”SO2N(X6)(X6), â€”N(X)SO2-phenyl, â€”N(X6)SO2X6, â€”CONX11X12, â€”SO2NX11X12, â€”NX6SO2X12, â€”NX6CONX11X12, â€”NX6SO2NX11X12, â€”NX6C(O)X12, imidazolyl, thiazolyl and tetrazolyl, provided that if A1 is optionally substituted with methylenedioxy then it can only be substituted with one methylenedioxy; where X11 is hydrogen or optionally substituted (C1-C6)alkyl; the optionally substituted (C1-C6)alkyl defined for X11 is optionally independently substituted with phenyl, phenoxy, (C1-C6)alkoxycarbonyl, â€”S(O)m(C1-C6)alkyl, 1 to 5 halogens, 1 to 3 hydroxy, 1 to 3 (C1-C10)alkanoyloxy or 1 to 3 (C1-C6)alkoxy; X12 is hydrogen, (C1-C6)alkyl, phenyl, thiazolyl, imidazolyl, furyl or thienyl, provided that when X12 is not hydrogen, X12 is optionally substituted with one to three substituents independently selected from the group consisting of Cl, F, CH3, OCH3, OCF3 and CF3; or X11 and X12 are taken together to form â€”(CH2)râ€”L1â€”(CH2)râ€”; where L1 is C(X2)(X2), O, S(O)m or N(X2); r for each occurrence is independently 1, 2 or 3; X2 for each occurrence is independently hydrogen, optionally substituted (C1-C6)alkyl, or optionally substituted (C3-C7)cycloalkyl, where the optionally substituted (C1-C6)alkyl and optionally substituted (C3-C7)cycloalkyl in the definition of X2 are optionally independently substituted with â€”S(O)m(C1-C6)alkyl, â€”C(O)OX3, 1 to 5 halogens or 1-3 OX3; X3 for each occurrence is independently hydrogen or (C1-C6)alkyl; X6 is independently hydrogen, optionally substituted (C1-C6)alkyl, (C2-C6)halogenated alkyl, optionally substituted (C3-C7)cycloalkyl, (C3-C7)-halogenated cycloalkyl, where optionally substituted (C1-C6)alkyl and optionally substituted (C3-C7)cycloalkyl in the definition of X6 is optionally independently substituted by 1 or 2 (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy, carboxyl, CONH2, â€”S(O)m(C1-C6)alkyl, carboxylate (C1-C4)alkyl ester, or 1H-tetrazol-5-yl; or X7 is hydrogen or (C1-C6)alkyl optionally substituted with hydroxyl; and m for each occurrence is independently 0, 1 or 2; with the proviso that: X6 and X12 cannot be hydrogen when it is attached to C(O) or SO2 in the form C(O)X6, C(O)X12, SO2X6 or SO2X12; and when R6 is a bond then L is N(X2) and each r in the definition â€”(CH2)râ€”Lâ€”(CH2)râ€” is independently 2 or 3.