Patent IL-136118-A (IL)
Title: Compositions for stimulating neurite growth
IPC: C07C69/035
Filed: 1996-06-06
Abstract: A pharmaceutically acceptable composition comprising: (a) a neurotrophic amount of a compound with affinity for FKBP12 of the formula and pharmaceutically acceptable derivatives thereof, wherein A is O, NH, or N-(C1-C4 alkyl); wherein B is hydrogen, CHL-Ar, (C1-C6) - straight or branched alkyl, (C2-C6)-straight or branched alkyl, (C2-C6) - straight or branched alkenyl, (C5-C7) - cycloalkyl, (C5-C7) - cycloalkenyl, or Ar substituted (C1-C6) - alkyl or (C2-C6) - alkenyl, or 3675 כ" ו בכסלו התשס" ג - December 1, 2002 wherein L and Q are independently hydrogen, (C1-C6) - straight or branched alkyl or (C2-C6) - straight or branched alkenyl; and T is Ar or substituted cyclohexyl with substituents at positions 3 and 4 which are independently selected from the group consisting of hydrogen, hydroxyl, O-(C1-C4) - alkyl or O-(C2-C4) - alkenyl and carbonyl; wherein Ar is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl and phenyl having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, CF3, (C1-C6) - straight or branched alkyl or (C2-C6) - straight or branched alkenyl, O-(C1-C4) - straight or branched alkyl or O-((C2-C4) - straight or branched alkenyl), O-benzyl, O-phenyl, amino and phenyl; D is U; E is either O or CH-U, provided that if D is hydrogen, then E is CH-U or if E is O then D is not hydrogen; wherein each U is independently selected from hydrogen, O-(C1-C4) - straight or branched alkyl or O-((C2-C4) - straight or branched alkenyl), (C1-C6) - straight or branched alkyl or (C2-C6) - straight or branched alkenyl, (C5-C7) - cycloalkyl or (C5-C7) - cycloalkenyl substituted with (C1-C4) - straight or branched alkyl or (C2-C4) - straight or branched alkenyl, 2-indolyl, 3-indolyl, [(C1-C4) - alkyl] - Ar, [(C2-C4) - alkenyl] - Ar, or Ar; J is hydrogen or C1 or C2 alkyl; K is (C1-C4) - straight or branched alkyl, benzyl or cyclohexylmethyl; or J and K are taken together to form a 5-7 membered heterocyclic ring which may contain an O, S, SO or SO2 substituent therein; the stereochemistry at carbon position 1 is R or S; provided that when J and K are taken together to form a 5-6 membered heterocyclic ring; and D is hydrogen; then, E is CH-U; provided that when J and K are taken together to form a 6-membered heterocyclic ring; D is U; E is O and D is not hydrogen; and when A is O, D is 1, 1-dimethyl-1-propyl, then B is not 3-cyclohexylpropyl, 3-phenylpropyl, or 3-(3', 4', 5'-trimethoxphenyl) propyl; when A is O, D is 3, 4, 5-trimethoxyphenyl, then B is not 4- (4'-methoxyphenyl) butyl; and when A is O, B is ethyl, then D is not methyl, ethyl, isopropyl, 2-methylpropyl, t-butyl, 1, 1-dimethyl-1-propyl, phenyl or benzyl; provided that when J and K are taken together to form a 5-membered heterocyclic ring; D is U; E is O and D is not hydrogen; and when: A is O, NH, or N-(C1-C4 alkyl); D is (C1-C6) - straight or branched alkyl, (C2-C6) - straight or branched alkenyl, (C5-C7) - cycloalkyl substituted with (C1-C4) - straight or branched alkyl or (C2-C4) - straight or branched alkenyl, or Ar; and Ar is 1-naphthyl, 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl or phenyl; then B is not: (i) a (C1-C6) alkyl or (C2-C6) alkenyl chain substituted with substituted or unsubstituted 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl or phenyl; or (ii) a (C1-C6) alkyl or (C2-C6) alkenyl chain substituted with (C5-C7) - cycloakyl; (b) a neurotrophic factor; and (c) a pharmaceutically acceptable carrier. 3676 כ" ו בכסלו התשס" ג - December 1, 2002