Patent ID: 6369074
Filing Date: 2002-04-09
Classification: C07D

Abstract:
A compound of the formula wherein W is hydrogen, (C1-C6)alkyl optionally substituted with from one to three fluorine atoms, â€”S(O)vâ€”(C1-C6) alkyl wherein v is zero, one or two, halo, benzyloxy or (C1-C6)alkoxy optionally substituted with from one to three fluorine atoms;the dotted lines in formula lb indicate that one of the Xâ€²-Yâ€² and Yâ€²-Zâ€² bonds may optionally be a double bond; Xâ€² is selected from =CHâ€”, â€”CH2â€”, â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”N(R4)â€”, â€”NHâ€”, =Nâ€”, â€”CH[(C1-C6)alkyl]â€”, =C[(C1-C6)alkyl]â€”, â€”CH(C6H5)â€” and =C(C6H5)â€”; Yâ€² is selected form C=O, C=NR4, C=S, =CHâ€”, â€”CH2â€”, =C[(C1-C6)alkyl]â€”, â€”CH[(C1-C6)alkyl]â€”, =C(C6H5)â€”, â€”CH(C6H5)â€”, =Nâ€”, â€”NHâ€”, â€”N(R4)â€”, =C(halo)â€”, =C(OR4)â€”, =C(SR4)â€”, =C(NR4)â€”, â€”Oâ€”, =C(CF3)â€”, =C(CH2C6H5)â€”, â€”Sâ€” and SO2, wherein the phenyl moieties of said =C(C6H5)â€” and â€”CH(C6H5)â€” may optionally be substituted with from one to three substituents, independently selected from halo and trifluoromethyl, and wherein the alkyl moieties of said =[(C1-C6)alkyl]â€” and â€”[CH(C1-C6)alkyl]â€” may optionally be substituted with from one to three fluorine atoms; Zâ€² is selected from =CHâ€”, â€”CH2â€”, =Nâ€”, â€”NHâ€”, â€”Sâ€”, â€”N(R4)â€”, =C(C6H5)â€”, â€”CH(C6H5)â€”, =C[(C1-C6)alkyl]â€” and â€”CH[(C1-C6)alkyl]â€”; or Xâ€², Yâ€² and Zâ€², together with the two carbon atoms shared between the benzo ring and the Xâ€²Yâ€²Zâ€² ring, form a fused pyridine or pyrimidine ring; R2 is hydrogen; R3 is R4 is (C1-C6) alkyl or phenyl; X is (CH2)q wherein q is an integer from 1 to 6, and wherein any one of the carbon-carbon single bonds in said (CH2)q may optionally be replaced by a carbon-carbon double bond, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R14, and wherein any one of the carbon atoms of said (CH2)q may optionally be substituted with R15; m is an integer from 0 to 8, and any one of the carbon-carbon single bonds of (CH2)m, wherein both carbon atoms of such bond are bonded to each other and to another carbon atom in the (CH2)m chain, may optionally be replaced by a carbon-carbon double bond or a carbon-carbon triple bond, and any one of the carbon atoms of said (CH2)m may optionally be substituted with R17; R12 is a radical selected from hydrogen, (C1-C6) straight or branched alkyl, (C3-C7)cycloalkyl wherein one of the carbon atoms may optionally be replaced by nitrogen, oxygen or sulfur; aryl selected form biphenyl, phenyl, indanyl and naphthyl; heteroaryl selected from thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl and quinolyl; phenyl-(C2-C6)alkyl, benzhydryl and benzyl, wherein the point of attachment on R12 is a carbon atom unless R12 is hydrogen, and wherein each of said aryl and heteroaryl groups and the phenyl moieties of said benzyl, phenyl-(C2-C6)alkyl and benzhydryl may optionally be substituted with one or more substituents independently selected from halo, nitro, (C1-C10)alkyl optionally substituted with from one to three fluorine atoms, (C1-C10)alkoxy optionally substituted with from one to three fluorine atoms, amino, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxyâ€”(C1-C6)alkyl, (C1-C6)-alkylamino, (C1-C6)alkylâ€”Oâ€”C(=O)â€”, (C1-C6)alkylâ€”Oâ€”C(=O)â€”(C1-C6)alkyl, (C1-C6)alkylâ€”C(=O)â€”Oâ€”, (C1-C6)alkylâ€”C(=O)â€”(C1-C6)alkylâ€”Oâ€”, (C1-C6)alkylâ€”C(=O)â€”, (C1-C6)alkylâ€”C(=O)â€”(C1-C6)alkylâ€”, diâ€”(C1-C6)alkylamino, â€”C(=O)NHâ€”(C1-C6)alkyl, (C1-C6)â€”alkylâ€”C(=O)â€”NHâ€”(C1-C6)alkyl, â€”NHC(=O)H and â€”NHC(=O)â€”(C1-C6)alkyl; and wherein one of the phenyl moieties of said benzhydryl may optionally be replaced by naphthyl, thienyl, furyl or pyridyl; R13 is hydrogen, phenyl or (C1-C6)alkyl; or R12 and R13, together with the carbon to which they are attached, form a saturated carbocyclic ring having from 3 to 7 carbon atoms wherein one of said carbon atoms that is neither the point of attachment of the spiro ring nor adjacent to it may optionally be replaced by oxygen, nitrogen or sulfur; R14 and R15 are each independently selected from hydrogen, hydroxy, halo, amino, oxo(=O), cyano, hydroxyâ€”(C1-C6)alkyl, (C1-C6)alkoxyâ€”(C1-C6)alkyl, (C1-C6)alkylamino, diâ€”(c1-C16)alkylamino, (C1-C6)alkoxy, â€”C(=O)â€”OH, (C1-C6)alkylâ€”Oâ€”C(=O)â€”, (C1-C6)alkylâ€”Oâ€”C(=O)â€”(C1-C6alkyl, (C1-C6)alkylâ€”C(=O)â€”Oâ€”, (C1-C6)alkylâ€”C(=O)â€”(C1-C6)alkylâ€”Oâ€”, (C1-C6)alkylâ€”C(=O)â€”, (C1-C6)alkylâ€”C(=O)â€”(C1-C6)alkylâ€”, and the radicals set forth in the definition of R12; R16 is NHC(=O)R18, NHCH2R18, SO2R18, CO2H or one of the radicals set forth in any of the definitions of R12, R14 and R15; R17 is oximino (=NOH) or one of the radicals set forth in any of the definitions of R12, R14 and R15; and with the proviso that (a) when m is 0, one of R16 and R17 is absent and the other is hydrogen, (b) when R14 and R15 are attached to the same carbon atom, then either each of R14 and R15 is independently selected from hydrogen, fluoro, (C1-C6)alkyl, hydroxy-(C1-C6)alkyl and (C1-C6)alkoxy-(C1-C6)alkyl, or R14 and R15, together with the carbon to which they are attached, form a (C3-C6) saturated carbocyclic ring that forms a spiro compound with the nitrogen-containing ring to which they are attached; (c) R12 and R13 cannot both be hydrogen; (d) when R14 or R15 is attached to a carbon atom of X that is adjacent to the ring nitrogen, then R14 or R15, respectively, must be a substituent wherein the point of attachment is a carbon atom; (e) when m=1, one of the hydrogens of the (CH2)m group is absent; (f) when m=1 and R17 is oximino, then R17 cannot be attached to the same carbon atom as R16; and (g) when R3 is a group of the formula VII, then the fused bicyclic nucleus containing Xâ€², Yâ€² and Zâ€² must be benzoxazolyl, benzthiazolyl, benzimidazolyl, benzisoxazolyl, benzoisothiazolyl, indazolyl, indolyl, isoquinolinyl, benzofuryl, benzothienyl, oxindolyl, benzoxazolinonyl, benzthiazolinonyl, benzimidazolinonyl, benzimidazoliniminyl, dihydrobenzothienyl-S, S-dioxide, benztriazolyl, benzthiadiazolyl, benzoxadiazolyl or quinazolinyl; or a pharmaceutically acceptable salt of such compound.