Patent ID: 6172086
Filing Date: 2001-01-09
Classification: A61K,A61P

Abstract:
A method for stimulating neurite growth in a patient or in an ex vivo nerve cell comprising the step of administering to said patient or said nerve a neurotrophic amount of a compound having the formula (I): ##STR5##and pharmaceutically acceptable derivatives thereof, whereinB and D are independently: hydrogen, Ar, (C1-C6) straight or branched alkyl, (C2-C6) straight or branched alkenyl or alkynyl, (C5-C7) cycloalkyl substituted (C1-C6) straight or branched alkyl, (C5-C7) cycloalkyl substituted (C3-C6) straight or branched alkenyl or alkynyl, (C5-C7) cycloalkenyl substituted (C1-C6) straight or branched alkyl, (C1-C7) cycloalkenyl substituted (C3-C6) straight or branched alkenyl or alkynyl, Ar-substituted (C1-C6) straight or branched alkyl, Ar-substituted (C3-C6) straight or branched alkenyl or alkynyl;R.sub.1 is (C5-C7) cycloalkyl substituted (C1-C6) straight or branched alkyl, (C5-C7) cycloalkyl substituted (C3-C6) straight or branched alkenyl or alkynyl, (C5-C7) cycloalkenyl substituted (C1-C6) straight or branched alkyl, (C5-C7) cycloalkenyl substituted (C3-C6) straight or branched alkenyl or alkynyl, Ar-substituted (C1-C6) straight or branched alkyl, Ar-substituted (C3-C6) straight or branched alkenyl or alkynyl;wherein any one of the CH.sub.2 groups of said alkyl chains in R.sub.1, B and D is optionally replaced by O, S, SO, SO.sub.2 or NR;wherein R is hydrogen, (C1-C6) straight or branched alkyl, (C3-C4) straight or branched alkenyl or alkynyl, or (C1-C4) bridging-alkyl wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl chain to form a ring, and wherein said ring is optionally fused to Ar;wherein each Ar is independently selected from phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyraxolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isotriazolyl, 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, 1,2,3,4-tetrahydroisoquinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl and phenoxazinyl; andwherein each Ar is optionally and independently substituted with one to three substituents independently selected from hydrogen, halogen, hydroxyl, nitro, --SO.sub.3 H, trifluoromethyl, trifluoromethoxy, (C1-C6) straight or branched alkyl, O-((C1-C6) straight or branched alkyl), O-benzyl, O-phenyl, 1,2-methylenedioxy, --NR.sub.5 R.sub.6, carboxyl, N-(C1-C6 straight or branched alkyl or C3-C5 straight or branched alkenyl) carboxamide, N,N-di-((C1-C6) straight or branched alkyl or (C3-C5) straight or branched alkenyl), carboxamide, morpholinyl, piperidinyl, O--M, CH.sub.2 --(CH.sub.2).sub.q --M, O--(CH.sub.2).sub.q --M, (CH.sub.2).sub.q --O--M, and CH.dbd.CH--M;wherein R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, (C1-C6) straight or branched alkyl, (C2-C6) straight or branched alkenyl or alkynyl, benzyl or R.sub.5 and R.sub.6 are taken together to form a 5-7 membered heterocyclic ring;M is selected from the group consisting of 4-methoxyphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazyl, quinolyl, 3,5-dimethylisoxazoyl, 2-methylthioazoyl, thiazoyl, 2-thienyl, 3-thienyl, 4-thienyl and pyrimidyl; andq is 0-2;J and K are taken together with the nitrogen and carbon atoms to which they are bound to form a 5-7 membered heterocyclic ring which may contain a heteroatom selected from O, S, SO or SO.sub.2 ;X is selected from the group consisting of Ar, --OR.sub.2, and --N(R.sub.3) R.sub.4 ;wherein R.sub.2 has the same definition as R.sub.1 ;R.sub.3 and R.sub.4 independently have the same definitions as B and D; or R.sub.3 and R.sub.4 are taken together to form a 5-7 membered heterocyclic aliphatic or aromatic ring; andm is 0 or 1.