Patent ID: 6713484
Filing Date: 2004-03-30
Classification: A61K,A61P,C07D

Abstract:
A compound of Formula 1: where:B and E are nitrogen, with the remaining atom(s) carbon; X is NH or NR7, such that R7 is lower alkyl (1-4 carbon atoms), OH, NH2, lower alkoxy (1-4 carbon atoms) or lower monoalkylamino (1-4 carbon atoms); n is 0, 1, 2; R1 is H or lower alkyl (1-4 carbon atoms); if n is 2, R1 is independently H or lower alkyl (1-4 carbon atoms) on either linking carbon atom; R2 is lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), cycloalkoxy (3-8 carbon atoms), nitro, halo (fluoro, chloro, bromo, iodo), lower perfluoroalkyl (1-4 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms; â€”Oâ€”C(O)R), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms), hydroxymethyl, lower acyl (1-4 carbon atoms; â€”C(O)R), cyano, lower thioalkyl (1-4 carbon atoms), lower sulfinylalkyl (1-4 carbon atoms), lower sulfonylalkyl (1-4 carbon atoms), thiocycloalkyl (3-8 carbon atoms), sulfinylcycloalkyl (3-8 carbon atoms), sulfonylcycloalkyl (3-8 carbon atoms), sulfonamido, lower mono or dialkylsulfonamido (1-4 carbon atoms), mono or dicycloalkylsulfonamido (3-8 carbon atoms), mercapto, carboxy, carboxamido (â€”C(O)â€”NH2), lower mono or dialkylcarboxamido (1-4 carbon atoms), mono or dicycloalkylcarboxamido (3-8 carbon atoms), lower alkoxycarbonyl (1-4 carbon atoms), cycloalkoxycarbonyl (3-8 carbon atoms), lower alkenyl (2-4 carbon atoms), cycloalkenyl (4-8 carbon atoms), lower alkynyl (2-4 carbon atoms), or two R2 taken together on contiguous carbon atoms can form a carbocyclic ring of 5-7 members or a monounsaturated 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, furanyl, pyrrolidyl, piperidinyl, thiolanyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morpholino or thiomorpholino ring; and m is 0-3; wherein Ar is phenyl, thienyl, furanyl, pyrrolyl, pyridyl, pyrimidyl, imidazoyl, pyrazinyl, oxazolyl, thiazolyl, naphthyl, benzothienyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl or quinazolinyl; R3, R4, R5 and R6 are independently, H, lower alkyl (1-4 carbon atoms), cycloalkyl (3-8 carbon atoms), lower alkoxy (1-4 carbon atoms), cycloalkoxy (3-8 carbon atoms), hydroxy, lower acyloxy (1-4 carbon atoms), amino, lower mono or dialkylamino (1-4 carbon atoms), lower mono or dicycloalkylamino (3-8 carbon atoms), lower alkyl (1-4 carbon atoms) or cycloalkyl (3-8 carbon atoms), carbonato (â€”OC(O)OR) where the R is lower alkyl of 1 to 4 carbon atoms or cycloalkyl of 3-8 carbon atoms; or ureido or thioureido or Nâ€” or Oâ€” linked urethane any one of which is optionally substituted by mono or di-lower alkyl (1-4 carbon atoms) or cycloalkyl (3-8 carbon atoms); or lower thioalkyl (1-4 carbon atoms), thiocycloalkyl (3-8 carbon atoms), mercapto, lower alkenyl (2-4 carbon atoms), hydrazino,Nâ€²-lower alkylhydrazino (1-4 carbon atoms), lower acylamino (1-4 carbon atoms), hydroxylamino, lower O-alkylhydroxylamino (1-4 carbon atoms; or any two of R3, R4, R5 or R6 talken together on contiguous carbon atoms form a carbocyclic ring of 5-7 members or a monounsaturated ring selected from the group consisting of 1,3-dioxolanyl, 1,4-dioxanyl, 1,4-dioxepinyl, pyranyl, furanyl, pyi-rolidyl, piperidinyl, thiolanyl, oxazolanyl, thiazolanyl, diazolanyl, piperazinyl, morphiolino and thionmorpholino ring; any lower alkyl group substituent on any of the substituents in R3-R6 is optionally substituted with one or more groups selected from the group consisting of hydroxy, amino, lower mono alkylamino, lower dialkylamino, N-pyrrolidyl, N-piperidinyl, N-pyridinium, N-morpholino, N-thiomorpholino and N-piperazino groups; if B or E are nitrogen, then any of R3-R6 on a neighboring carbon atom to one of the nitrogen atoms can not be either OH or SH; if any of the substitutents R1, R2, R3, R4, R5 or R6 contain chiral centers, or in the case of R1create chiral centers on the linking atoms, then all stereoisomers thereof both separately and as racemic and/or diastercoisomeric mixtures are included; or a pharmaceutical salt or hydrate thereof; with the further provisos that when E and B are nitrogen and D and A are carbon then R4 and R5 substitutents must not be hydrogen, lower alkyl (1-4 carbon atoms) or lower alkoxy (1-4) carbons; E and B are nitrogen and D and A are carbon, R and R are not present; or R5 is hydrogen, X is NH, n is 0, 1 or 2, R1is H or lower alkyl; Ar is aryl unsubstituted or substituted by halo, hydroxy or amino; or n is 1 or 2, R1is H or lower alkyl; and Ar is a heterocyclic ring, then R4 cannot be hydrogen, amino, lower monoalkylamino unsubstituted or substituted by hydroxy, lower monocycloalkylamino unsubstituted or substituted by hydroxy, lower dialkylamino unsubstituted or substituted by hydroxy, or heterocyclicalkyl amino; or E and B are nitrogen and D and A are carbon, R3 and R6 are not present, R5 is hydrogen, X is NH, n is 0, 1 or 2, R1is H or lower alkyl; Ar is aryl, then R4 cannot be lower alkylthio; or E and B are nitrogen and D and A are carbon, R3 and R6 are not present, R1 is hydrogen, X is NH, n is 1, R1 is H, Ar is phenyl para substituted by diethylamino, then R4 cannot be amino; or E and B are nitrogen and D and A are carbon, R3 and R6 are not present, R5 is hydrogen, X is NH, n is 1, R1is H, Ar is 2-furanyl, then R4 cannot be ethylthio or that at least one of the group R3 and R5 or R4 and R5 substitutents must be other then hydrogen, lower alkyl (1-4 carbon atoms) or lower alkoxy (1-4 carbon atoms).