Patent ID: 6451801
Filing Date: 2002-09-17
Classification: A61P,C07D

Abstract:
A compound of formula Iâ€²: and geometrical isomers, enantiomers, diastereomers, and pharmaceutically acceptable salts thereof, wherein:X and Xâ€² independently are hydrogen, halo, alkyl, alkenyl, alkynyl, alkoxy, trifluoromethyl or â€”(Yâ€²)mâ€”Wâ€²; D is â€”CH&boxH; or &boxH;Nâ€”; R1 and R2 are both hydrogen or together are â€”(CH2)nâ€” in which n is equal to 0, 1, 2, or 3; m and mâ€² are independently 0 or 1; Y and Yâ€² are â€”L1â€” or â€”L2â€”V(Z)tâ€”L3â€” in which t is 0 or 1; L1 is alkylene, alkenylene, alkynylene, or one of the foregoing in which one or more methylenes are replaced by â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, â€”N(Q)â€”, or â€”N(R3)â€”; L2 is (a) alkylene, alkenylene, alkynylene, or one of the foregoing in which one or more methylenes are replaced by â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, â€”N(Qâ€²)â€”, or â€”N(R4)â€”, or (b) â€”L4â€”C(Oâ€”N(Qâ€²)â€” or â€”L4(Qâ€²)â€”, or (c) a direct bond; L3 and L4 independently are (a) alkylene, alkenylene, alkynylene, or one of the foregoing in which one or more methylenes are replaced by â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, â€”N(Qâ€³)â€”, or â€”N(R5)â€”, or (b) a direct bond; V is (a) a divalent arene, a divalent heteroarene, or a divalent saturated heterocycle when t is 0, or (b) a trivalent arene or trivalent heteroarene when t is 1; Q, Qâ€², and Qâ€³ independently are hydrogen, â€”AC(O)OR6, or â€”AC(O)NR6R7; W and Wâ€² independently are â€”N(OM)C(O)N(R8)R9, â€”N(R8)C(O)N(OM)R9, â€”N(OM)C(O)R8, â€”C(O)NR8R9, or â€”C(O)OR8, provided that at least one of W and Wâ€² is â€”N(OM)C(O)N(R8)R9, â€”N(R8)C(O)N(OM)R9, or â€”N(OM)C(O)R8; Z is â€”Aâ€³N(OMâ€²)C(O)N(R10)R11, â€”Aâ€³N(R10)C(O)N(OMâ€²)R11, â€”Aâ€³N(OMâ€²)C(O)R11, â€”Aâ€²C(O)N(OMâ€²)R11, â€”Aâ€²C(O)NR10R11, â€”Aâ€²C(O)OR10, halo, CH3, NR3R4, NR3C(O)R4, NR3C(O)R4, NO2, CN, CF3, S(O)2NR3R4, S(O)2R3, SR3, or S(O)R3; A, Aâ€² and Aâ€³ independently are a direct bond, alkylene, alkenylene, alkynylene, yloalkylaryl, yloarylalkyl, or diylodialkylarene or one of the foregoing in which one or more methylenes are replaced with â€”Oâ€”, â€”NHâ€”, â€”Sâ€”, â€”S(O)â€”, or â€”S(O)2â€” and/or one or more methylidenes are replaced by &boxH;Nâ€”; M and Mâ€² independently are hydrogen, an organic or inorganic anion, a pharmaceutically acceptable cation, acyl, alkyl, NH2C(O)â€” or (alkyl)OC(O)â€”; R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently hydrogen, alkyl, alkynyl, aryl, arylalkyl, alkylaryl, alkylarylalkyl, or one of the foregoing in which one or more methylenes are replaced by â€”Oâ€”, â€”NHâ€”, â€”Sâ€”, â€”S(O)â€”, or â€”S(O)2â€” and/or one or more methylidenes are replaced by &boxH;Nâ€”; provided that, other than the oxygens bound to the sulfurs in â€”S(O)â€” and â€”S(O)2â€”, when one or more methylenes are replaced with â€”Oâ€”, â€”NHâ€”, â€”Sâ€”, â€”S(O)â€”, or â€”S(O)2â€” and when one or more methylidenes are placed with &boxH;Nâ€”, such replacement does not result in two heteroatoms being covalently bound to each other; and further provided that when m is 0, W is not â€”C(O)NR8R9, or â€”C(O)OR8; and further provided that in the substituent â€”AC(O)OR6, R6 cannot be hydrogen when A is a direct bond; and wherein: optionally substituted means optionally substituted with one or more moieties selected from the group consisting of halo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano,; alkyl refers to a univalent C1 to C6 saturated straight, branched, or cyclic alkane moiety and is optionally substituted; alkenyl refers to a univalent C2-C6 straight, branched, or C5-6, cyclic hydrocarbon with at least one double bond and is optionally substituted; alkynyl refers to a univalent C2 to C6 straight or branched hydrocarbon with at least one triple bond and is optionally substituted; alkoxy refers to an alkyl moiety having a terminal â€”Oâ€” with free a valence; alkylene refers to an alkyl moiety in which a hydrogen atom has been removed to yield a divalent radical; alkenylene refers to an alkenyl moiety in which a hydrogen atom has been removed to yield a divalent radical; alkynylene refers to an alkynyl moiety in which a hydrogen atom has been removed to yield a divalent radical; aryl refers to a univalent phenyl, biphenyl, or napthyl and is optionally substituted; arylene and divalent arene refer to an aryl moiety in which a hydrogen atom has been removed to yield a divalent radical; trivalent arene refers to an arylene moiety in which a hydrogen atom has been removed to yield a trivalent radical; heteroarylene and divalent heteroarene refer to an arylene or divalent heteroarene that includes at least one sulfur, oxygen, or nitrogen in the aromatic ring, and is optionally substituted; trivalent heteroarene refers to a heteroarylene moiety in which a hydrogen atom has been removed to yield a trivalent radical.