公开(公告)号：WO1994019316A1

公开(公告)日：1994-09-01

申请号：PCT/SE1994000153

申请日：1994-02-24

Applicant: AKTIEBOLAGET ASTRA ,  THE UNIVERSITY OF MARYLAND ,  CORNELL RESEARCH FOUNDATION INC. ,  BJÖRK, Susanna, Karin, Maria ,  CARPENTIER, Barry, K. ,  GOTTHAMMAR, Kristina, Brigitta ,  LINDERBERG, Mat, Torbjörn ,  LUTHMAN, Per, Johan ,  PERSSON, Kerstin, Margareta, Irma ,  SCHWARCZ, Robert

Inventor： AKTIEBOLAGET ASTRA ,  THE UNIVERSITY OF MARYLAND ,  CORNELL RESEARCH FOUNDATION INC.

IPC: C07C229/64

CPC classification number: C07D333/20 ,  C07C45/27 ,  C07C47/277 ,  C07C205/37 ,  C07C205/59 ,  C07C205/60 ,  C07C229/64

Abstract: The present invention relates to novel derivatives of 3-hydroxyanthranilic acid, 3-HANA, of general formula (I) wherein R and R are the same or different and selected from H, alkyl, aryl and arylalkyl; X and Y are the same or different and selected from alkoxy, aryloxy, alkyl, alkylthio, arylthio, fluoroalkyl, halogen, cyano, OSO2CH3, OSO2CF3, OCF3 and SCF3 with the proviso that the compound of formula (I) wherein R and R = H, X = Br and Y = Me is excluded; or a pharmaceutically acceptable salt thereof, methods and intermediates for their preparation, novel pharmaceutical compositions and the use thereof for inhibiting the enzyme 3-hydroxyanthranilate oxygenase, 3-HAO, responsible for the production of the endogenous neurotoxin quinolinic acid, QUIN.

Abstract translation: 本发明涉及通式（I）的3-羟基邻氨基苯甲酸的新型衍生物，其中R 1和R 2相同或不同并且选自H，烷基，芳基和芳基烷基; X和Y相同或不同，并且选自烷氧基，芳氧基，烷基，烷硫基，芳硫基，氟烷基，卤素，氰基，OSO 2 CH 3，OSO 2 CF 3，OCF 3和SCF 3，条件是其中R 1， 和R 2 = H，X = Br和Y = Me; 或其药学上可接受的盐，其制备方法和中间体，新型药物组合物及其用于抑制负责内源性神经毒素喹啉酸QUIN的3-羟基邻氨基苯甲酸酶加氧酶3-HAO的用途。

公开(公告)号：WO1994019315A1

公开(公告)日：1994-09-01

申请号：PCT/SE1994000152

申请日：1994-02-22

Applicant: AKTIEBOLAGET ASTRA ,  THE UNIVERSITY OF MARYLAND ,  BJÖRK, Susanna, Karin, Maria ,  GOTTHAMMAR, Kristina, Birgitta ,  LINDERBERG, Mats, Torbjörn ,  LUTHMAN, Per, Johan ,  PERSSON, Kerstin, Margareta, Irma ,  SCHWARCZ, Robert

Inventor： AKTIEBOLAGET ASTRA ,  THE UNIVERSITY OF MARYLAND

IPC: C07C229/64

CPC classification number: C07C205/59 ,  C07C205/26 ,  C07C205/37 ,  C07C229/64 ,  C07C229/70 ,  C07C255/59 ,  C07C2602/10

Abstract: The present invention relates to novel derivatives of 3-hydroxyanthranilic acid, 3-HANA, of general formula (I), wherein R and R are the same or different and selected from H and alkyl; X is selected from alkylthio, arylthio, aryloxy, halogen and cyano; R , R are the same or different and selected from halogen, methyl, fluoroalkyl, cyano and Z-R wherein Z is selected from CHn, NHm, O, S, SO2 and CO wherein n = 1 or 2; m = 0 or 1 and R is selected from alkyl, aryl and fluoroalkyl; or R and R together form a saturated or unsaturated ring system Y-V-Z wherein Y and Z, independently of each other, are as defined for Z above and V is selected from C1-C3 alkylene or alkenylene, -N = , -N = N- and (a), wherein R7 = H or alkyl; or a pharmaceutically acceptable salt thereof, methods and intermediates for their preparation, novel pharmaceutical compositions and the use thereof for inhibiting the enzyme 3-hydroxy-anthranilate oxygenase, 3-HAO, responsible for the production of the endogenous neurotoxin quinolinic acid, QUIN.

Abstract translation: 本发明涉及通式（I）的3-羟基邻氨基苯甲酸3-HANA的新衍生物，其中R 1和R 2相同或不同并且选自H和烷基; X选自烷硫基，芳硫基，芳氧基，卤素和氰基; R 3，R 4相同或不同，并且选自卤素，甲基，氟烷基，氰基和ZR 5，其中Z选自CH n，NH m，O，S，SO 2和CO，其中n = 1或 2; m = 0或1，R 5选自烷基，芳基和氟烷基; 或R 3和R 4一起形成饱和或不饱和的环系YVZ，其中Y和Z彼此独立地如上述Z所定义，V选自C 1 -C 3亚烷基或亚烯基，-N = ，-N = N-和（a），其中R7 = H或烷基; 或其药学上可接受的盐，其制备方法和中间体，新型药物组合物及其用于抑制负责产生内源性神经毒素喹啉酸QUIN的3-羟基 - 邻氨基苯甲酸加氧酶3-HAO的用途。