发明名称 2-Acyl, N-substituted pyrrolidine derivative inhibitors of rotamase enzyme activity and their use in treating neurological disorders
摘要 Disclosed is the use of a compound of formula (1), wherein: R1 is selected from the group consisting of a C1 -C9 straight or branched chain alkyl or alkenyl group optionally substituted with C3 -C8 cycloalkyl, C3 or C5 cycloalkyl, C5 -C7 cycloalkenyl, where the alkyl, alkenyl, cycloalkyl or cycloalkenyl groups may be optionally substituted with C1 -C4 alkyl, C1 -C4 alkenyl, or hydroxy, or Ar1, where Ar1 is selected from the group consisting of 1-napthyl, 2-napthyl, 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thiazolyl, 2-thienyl, 3-thienyl, 2-,3-, or 4-pyridyl, and phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C1 -C6 straight or branched alkyl or alkenyl, C1 -C4 alkoxy or C1 -C4 alkenyloxy, phenoxy, benzyloxy, and amino; X is selected from the group consisting of oxygen, sulfur, CH2, or H2; Y is selected from the group consisting of oxygen or NR2, where R2 is hydrogen or C1 -C6 alkyl; and Z is selected from the group consisting of C1 -C7 straight or branched chain alkyl or alkenyl, wherein the alkyl or alkenyl chain is substituted in one or more positions with Ar1 as defined above, C3 -C8 cycloalkyl, cycloalkyl connected by a C1 -C6 straight or unbranched alkyl or alkenyl chain, or Ar2 where Ar2 is selected from the group consisting of 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2- thiazolyl, 2-thienyl, 3-thienyl, 2-, 3-, or 4-pyridyl, and phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C1-C6 straight or branched alkyl or alkenyl, C1-C4 alkoxy or C1-C4 alkenyloxy, phenoxy, benzyloxy, and amino; Z may also be the fragment of formula (2), wherein R3 is selected from the group consisting of straight or branched alkyl C1-C8 optionally substituted with C3-C8 cycloalkyl, or Ar1 as defined above, and unsubstituted Ar1; X2 is O or NR5, where R5 is selected from the group consisting of hydrogen, C1-C6 straight or branched alkyl and alkenyl; R4 is selected from the group consisting of phenyl, benzyl, C1-C5 straight or branched alkyl or alkenyl, and C1 -C5 straight or branched alkyl or alkenyl substituted with phenyl. The compound is used in the preparation of a medicament for promoting neuronal growth and regeneration, for treating neurological disorder, for promoting neuroregeneration or for preventing neurodegeneration. Such diseases include Alzheimer's disease, Parkinson's disease and amytrophic lateral sclerosis.
申请公布号 NZ310292(A) 申请公布日期 2001.04.27
申请号 NZ19960310292 申请日期 1996.06.05
申请人 GUILFORD PHARMACEUTICALS INC 发明人 HAMILTON, GREGORY S;STEINER, JOSEPH P
分类号 C12N9/99;A61K31/00;A61K31/40;A61K31/401;A61K31/4025;A61K31/405;A61K31/427;A61K31/44;A61K31/4427;A61K31/443;A61K31/4433;A61K31/4439;A61K31/444;A61K31/454;A61K38/00;A61K45/00;A61P21/00;A61P21/02;A61P25/00;A61P25/02;A61P25/14;A61P25/16;A61P25/24;A61P25/28;A61P37/00;A61P43/00;C07B53/00;C07D207/16;C07D401/04;C07D401/06;C07D405/06;C07D405/10;C07D405/12;C07D407/04;C07D409/04;C07D409/06;C07D409/12;C07D409/14;C07D417/02;C07D417/04;C07D417/12;C07K5/078;(IPC1-7):A61K31/40 主分类号 C12N9/99
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