公开(公告)号：US5516936A

公开(公告)日：1996-05-14

申请号：US137100

申请日：1993-12-27

申请人： Robert S. Phillips ,  Rajesh K. Dua

发明人： Robert S. Phillips ,  Rajesh K. Dua

IPC分类号： A01N37/44 ,  A01N41/10 ,  A61K31/195 ,  A61K31/66 ,  A61P25/00 ,  A61P25/08 ,  A61P43/00 ,  C07C229/22 ,  C07C313/06 ,  C07C317/48 ,  C07C323/58 ,  C07F9/30 ,  C07F9/36 ,  C07C321/24

CPC分类号： A61K31/66 ,  A61K31/195 ,  C07C317/48 ,  C07C323/58

摘要： The present invention provides inhibitors of kynureninase having the formula ##STR1## where X is CHOH, S, SO.sub.2, SO, SONH, PO.sub.2 H or PONH.sub.2, R.sub.A and R.sub.B, independently of one another, are H, a halogen, CF.sub.3 or a small alkyl group having one to three carbon atoms; A is a H or an acetyl group; R.sub.1 is H, NH.sub.2, NR.sub.6 R.sub.7, NO.sub.2, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms, wherein: R.sub.6 and R.sub.7, independently of one another, are H, a formyl group or a small alkyl group having from one to three carbon atoms with the exception that only one of R.sub.6 or R.sub.7 can be a formyl group; R.sub.2 is OH, H, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms; and R.sub.3, R.sub.4 and R.sub.5, independently of one another, are H, halogen, CF.sub.3, NO.sub.2, NH.sub.2, or small alkyl group having from one to three carbon atoms. In particular, compounds of this formula in which X is CHOH, S or SO.sub.2 are provided. In compounds of this formula in which X is CHOH, those having the (.alpha.S,.gamma.S) configuration or the (.alpha.R,.gamma.R) configuration when R.sub.A or R.sub.B is a hydrogen, are more potent inhibitors of kynureninase. Inhibitors of mammalian kynureninase are of particular use in therapy for certain neurological disorders.

摘要翻译： PCT No.PCT / US92 / 03198 Sec。 371日期1993年12月27日第 102（e）日期1993年12月27日PCT提交1992年4月17日PCT公布。 WO92 / 18003 PCT出版物 本发明提供具有式“IMAGE”的犬尿胆碱酯酶抑制剂，其中X为CHOH，S，SO2，SO，SONH，PO2H或PONH2，RA和RB，彼此独立地为H，a 卤素，CF 3或具有1至3个碳原子的小烷基; A是H或乙酰基; R 1是H，NH 2，NR 6 R 7，NO 2，卤素，CF 3或具有1至3个碳原子的小烷基，其中：R 6和R 7彼此独立地是H，甲酰基或具有 一至三个碳原子，只有R6或R7中只有一个可以是甲酰基; R2是OH，H，卤素，CF3或具有1-3个碳原子的小烷基; R 3，R 4和R 5彼此独立地是H，卤素，CF 3，NO 2，NH 2或具有1至3个碳原子的小烷基。 特别地，提供了其中X是CHOH，S或SO 2的该式的化合物。 在其中X是CHOH的该式的化合物中，当RA或RB是氢时，具有（αS，γS）构型或（αR，γR）构型的那些化合物是更有效的犬尿胆碱酶抑制剂。 哺乳动物犬尿胆碱酶的抑制剂在某些神经障碍的治疗中特别有用。

公开(公告)号：US5442104A

公开(公告)日：1995-08-15

申请号：US184788

申请日：1994-01-21

申请人： Robert S. Phillips ,  Rajesh K. Dua

发明人： Robert S. Phillips ,  Rajesh K. Dua

IPC分类号： A01N37/44 ,  A01N41/10 ,  A61K31/195 ,  A61K31/66 ,  A61P25/00 ,  A61P25/08 ,  A61P43/00 ,  C07C229/22 ,  C07C313/06 ,  C07C317/48 ,  C07C323/58 ,  C07F9/30 ,  C07F9/36 ,  C07C317/10 ,  C07C317/14 ,  C07C317/28

CPC分类号： A61K31/66 ,  A61K31/195 ,  C07C317/48 ,  C07C323/58

摘要： The present invention provides inhibitors of kynureninase having the formula ##STR1## where X is CHOH, S, SO.sub.2, SO, SONH.sub.2, PO.sub.2 H or PONH.sub.2, R.sub.a and R.sub.b, independently of one another are H, a halogen, CF.sub.3 or a small alkyl group having one to three carbon atoms; R.sub.1 is H, NH.sub.2, NR.sub.6 RT, NO.sub.2, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms, wherein: R.sub.6 and R.sub.7, independently of one another, are H, a formyl group or a small alkyl group having from one to three carbon atoms with the exception that only one of R.sub.6 or R.sub.7 can be a formyl group; R.sub.2 is OH, H, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms; and R.sub.3, R.sub.4 and R.sub.5, independently of one another, are H, halogen, CF.sub.3, NO.sub.2, NH.sub.2, or small alkyl group having from one to three carbon atoms. In particular, compounds of this formula in which X is CHOH, S or SO.sub.2 are provided. In compounds of this formula in which X is CHOH, those having the (.alpha.S,.gamma.S) configuration or the (.alpha.R,.gamma.R) configuration when R.sub.A or R.sub.B is a hydrogen, are more potent inhibitors of kynureninase. Inhibitors of mammalian kynureninase are of particular use in therapy for certain neurological disorders.

摘要翻译： 本发明提供具有式“IMAGE”的犬尿胆碱酯酶抑制剂，其中X为CHOH，S，SO2，SO，SONH2，PO2H或PONH2，Ra和Rb，彼此独立地为H，卤素，CF3或小烷基 具有一至三个碳原子; R1是H，NH2，NR6RT，NO2，卤素，CF3或具有1-3个碳原子的小烷基，其中：R6和R7彼此独立地是H，甲酰基或具有 一至三个碳原子，只有R6或R7中只有一个可以是甲酰基; R2是OH，H，卤素，CF3或具有1-3个碳原子的小烷基; R 3，R 4和R 5彼此独立地是H，卤素，CF 3，NO 2，NH 2或具有1至3个碳原子的小烷基。 特别地，提供了其中X是CHOH，S或SO 2的该式的化合物。 在其中X是CHOH的该式的化合物中，当RA或RB是氢时，具有（αS，γS）构型或（αR，γR）构型的那些化合物是更有效的犬尿胆碱酶抑制剂。 哺乳动物犬尿胆碱酶的抑制剂在某些神经障碍的治疗中特别有用。

公开(公告)号：US5254725A

公开(公告)日：1993-10-19

申请号：US689705

申请日：1991-04-18

申请人： Robert S. Phillips ,  Rajesh K. Dua

发明人： Robert S. Phillips ,  Rajesh K. Dua

IPC分类号： A61K31/195 ,  A61K31/66 ,  C07C317/48 ,  C07C323/58 ,  C07C229/36

CPC分类号： A61K31/66 ,  A61K31/195 ,  C07C317/48 ,  C07C323/58

摘要： The present invention provides inhibitors of kynureninase having the formula ##STR1## where R.sub.a and R.sub.b, independently of one another are H, a halogen, CF.sub.3 or a small alkyl group having one to three carbon atoms; R.sub.1 is NH.sub.2, NR.sub.6 R.sub.7, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms, wherein R.sub.6 and R.sub.7, independently of one another, are H, a formyl group or a small alkyl group having from one to three carbon atoms with the exception that only one of R.sub.6 or R.sub.7 can be a formyl group; R.sub.2 is OH, H, halogen, CF.sub.3 or a small alkyl group having from one to three carbon atoms; and R.sub.3, R.sub.4 and R.sub.5, independently of one another, are H, halogen, CF.sub.3 or small alkyl group having from one to three carbon atoms. In particular, compounds of formula I having the (.alpha.S,.gamma.S) configuration or (.alpha.R,.gamma.R) configuration when R.sub.A or R.sub.B is a halogen are more potent inhibitors of kynureninase. Inhibitors of mammalian kynureninase are of particular use in therapy for certain neurological disorders.

摘要翻译： 本发明提供了具有式“IMAGE”的犬尿胆碱酶抑制剂，其中R a和R b彼此独立地为H，卤素，CF 3或具有1-3个碳原子的小烷基; R1是NH2，NR6R7，卤素，CF3或具有1-3个碳原子的小烷基，其中R6和R7彼此独立地是H，甲酰基或具有1-3个碳原子的小烷基 除了R6或R7中只有一个可以是甲酰基; R2是OH，H，卤素，CF3或具有1-3个碳原子的小烷基; R 3，R 4和R 5彼此独立地为具有1至3个碳原子的H，卤素，CF 3或小烷基。 特别地，当RA或RB是卤素时，具有（αS，γS）构型或（αR，γR）构型的式I化合物是更强有力的犬尿胆碱酯酶抑制剂。 哺乳动物犬尿胆碱酶的抑制剂在某些神经障碍的治疗中特别有用。