Patent ID: 6228872
Filing Date: 2001-05-08
Classification: A61P,C07D

Abstract:
A compound having the formula (I) ##STR75##and pharmaceutically acceptable salts thereof, wherein:Z is O, NH, or N(C.sub.1 -C.sub.3)-alkyl;X is O or F.sub.2 ;B and L are independently hydrogen, (C.sub.1 -C.sub.4)-alkyl, or benzyl;J and K together with the atoms to which they are attached form a 5-membered ring containing one nitrogen as the only heteroatom;wherein the stereochemistry at carbon position 1 is R or S;D is (C.sub.1 -C.sub.6)-straight or branched alkyl, (C.sub.2 -C.sub.6)-straight or branched alkenyl, (C.sub.5 -C.sub.7)-cycloalkyl or (C.sub.5 -C.sub.7)-cycloalkenyl substituted with (C.sub.1 -C.sub.4)-straight or branched alkyl or (C.sub.2 -C.sub.4)-straight or branched alkenyl, O-(C.sub.1 -C.sub.4)-straight or branched alkyl, O-(C.sub.2 -C.sub.4)-straight or branched alkenyl, 2-indolyl, 3-indolyl, [(C.sub.1 -C.sub.4)-alkyl or (C.sub.2 C.sub.4)-alkenyl]-Ar or Ar;Ar is a carbocyclic aromatic group selected from the group consisiting of phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, fluorenyl, and anthracenyl; or a heterocyclic aromatic group selected from the group consisting of 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, benzo[b]thiophenyl, 1H-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl;Ar may contain one to three substituents which are independently selected from the group consisting of hydrogen, halogen, hydroxyl, hydroxymethyl, nitro, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.6)-straight or branched alkyl, (C.sub.2 -C.sub.6)-straight or branched alkenyl, O-[(C.sub.1 -C.sub.4)-straight or branched alkyl], O-benzyl, O-phenyl, 1,2-methylenedioxy, amino, carboxyl, N-[(C.sub.1 -C.sub.5)-straight or branched alkyl or (C.sub.2 -C.sub.5)-straight or branched alkenyl] carboxamides, N,N-di-[(C.sub.1 -C.sub.5)-straight or branched alkyl or (C.sub.2 -C.sub.5)-straight or branched alkenyl] carboxamides, N-morpholinecarboxamide, N-benzylcarboxamide, N-thiomorpholinocarboxamide, N-picolinoylcarboxamide, O--W, CH.sub.2 --(CH.sub.2).sub.p --W, O--(CH.sub.2).sub.p --W, (CH.sub.2).sub.p --O--W, and CH.dbd.CH--W;W is 4-methoxyphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazyl, quinolyl, 3,5-dimethylisoxazoyl, isoxazoyl, 2-methylthiazoyl, thiazoyl, 2-thienyl, 3-thienyl, or pyrimidyl; p is 0-2;Q and A are independently hydrogen, Ar, (C.sub.1 -C.sub.10)-straight or branched alkyl, (C.sub.2 -C.sub.10)-straight or branched alkenyl or alkynyl, provided the carbon atom having the triple bond in the alkynyl group is not directly bonded to the nitrogen atom of the core; (C.sub.5 -C.sub.7)-cycloalkyl substituted (C.sub.1 -C.sub.6)-straight or branched alkyl, (C.sub.2 -C.sub.6)-straight or branched alkenyl or alkynyl, (C.sub.5 -C.sub.7)-cycloalkenyl substituted (C.sub.1 -Ce)-straight or branched alkyl, (C.sub.2 -C.sub.6)-straight or branched alkenyl or alkynyl, or Ar-substituted (C.sub.1 -C.sub.6)-straight or branched alkyl, (C.sub.2 -C.sub.6)-straight or branched alkenyl or alkynyl wherein, in each case, any one of the CH.sub.2 groups of said alkyl, alkenyl or alkynyl chains may be optionally replaced by a heteroatom selected from the group consisting of O, S, SO, SO.sub.2, N, and NR, wherein R is selected from the group consisting of hydrogen, (C.sub.1 -C.sub.4)-straight or branched alkyl, (C.sub.2 -C.sub.4)-straight or branched alkenyl or alkynyl, and (C.sub.1 -C.sub.4)-bridging alkyl wherein a bridge is formed between the nitrogen and a carbon atom of said heteroatom-containing chain to form a ring, and wherein said ring is optionally fused to an Ar group; or ##STR76##G is hydrogen, (C.sub.1 -C.sub.6)-straight or branched alkyl or (C.sub.2 -C.sub.6)-straight or branched alkenyl or alkynyl; andT is Ar or substituted 5-7 membered cycloalkyl with substituents at positions 3 and 4 which are independently selected from the group consisting of oxo, hydrogen, hydroxyl, O-(C.sub.1 -C.sub.4)-alkyl, or O-(C.sub.2 -C.sub.4)-alkenyl.