Patent EA-001625-B1 (EA)
Title: 3-alkoxyisoxazol-4-yl-substituted 2-amino carboxylic acid derivatives
Inventor: BANG-ANDERSEN BENNY
IPC: A61P25/28
Filed: 1997-10-03
Abstract: 1. A (3-alkoxyisoxazol-4-yl)substituted 2-amino carboxylic acid derivative or sulfur-containing analog thereof having general Formula I or II   wherein R1 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, cycloalk(en)yl, cycloalk(en)yl-C1-6-alk(en/yn)yl or phenyl-C1-6-alk(en/yn)yl, the phenyl group being optionally substituted with CF3, halogen, C1-6-alkyl or C1-6-alkoxy; A is a bond or a spacer group selected from C1-6-alkylene, C2-6-alkenylene, or C2-6-alkynylene, and cycloalkylene; B is a group -CRa(NRbRc)-COOR5 wherein Ra-Rc are independently hydrogen or C1-6-alkyl, and R5 is defined as R1 or pivaloyloxymethyl, or B is a group of Formula III   wherein R2, R3 and R4 are independently selected from the group consisting of a) hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, cycloalk(en)yl, cycloalk(en)yl-C1-6-alk(en/yn)yl, phenyl-C1-6-alkyl, thienyl-C1-6-alkyl, and b) C1-6-alkyl, C2-6-alkenyl and C2-6-alkynyl in which one or more carbon atoms are replaced by N, O, and/or S, or R3 and R4 are connected, thereby forming a C2-C6-alkylene, C2-C6-alkenylene or C2-C6-alkynylene group, or R4 and R2 are connected in order to form a C1-C3-alkylene, C2-C3-alkenylene or C2-C3-alkynylene group optionally mono- or disubstituted with hydroxy or methyl, or to form CH2-O-CH2; E is COOR6, where R6 is defined as R5; X is O or S; Y is O or S; or a pharmaceutically acceptable salt thereof. 2. A compound of Claim 1 which has Formula I. 3. A compound of Claim 1 which has Formula II. 4. A compound of any of Claim 1-3, wherein E is COOR6, wherein R6 is not hydrogen, and preferably R6 is C1-6-alkyl, phenyl-C1-6-alk(en/yn)yl or pivaloyloxymethyl. 5. A compound of any of Claim 1-3, wherein E is CO-OH. 6. A compound of any of Claim 1-5, wherein B is a group of the formula -CRa(NRbRc)-COOR5. 7. A compound of Claim 6, wherein Rb and Rc are hydrogen and Ra is hydrogen or C1-6-alkyl, preferably hydrogen or methyl. 8. A compound of Claim 6 or 7, wherein R5 is hydrogen. 9. A compound of Claim 6 or 7, wherein R5 is not hydrogen and preferably R5 is C1-6-alkyl, phenyl-C1-6-alk(en/yn)yl or pivaloyloxymethyl. 10. A compound of any of Claim 1-5, wherein B is a group of the formula III. 11. A compound of Claim 10, wherein R2, R3 and R4 are hydrogen or C1-6-alkyl, or R4 and R2 are connected in order to form a C1-3-alkylene group. 12. A compound of Claim 11, wherein each of R2, R3 and R4 are hydrogen. 13. A compound of any of Claim 1-12, wherein X is oxygen. 14. A compound of any of Claim 1-12, wherein X is sulfur. 15. A compound of any of Claim 1-14, wherein Y is oxygen. 16. A compound of any of Claim 1-14, wherein Y is sulfur. 17. A compound of any of Claim 1-16, wherein R1 is C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl, preferably methyl, ethyl, propyl or propargyl. 18. A compound of any of Claim 1-17, wherein A is a bond or C1-3-alkylene, preferably - methylene. 19. A compound of Claim 2, wherein A is a bond or C1-C3-alkylene, B is a group of formula -CH(NH2)-COOH or a group of Formula III wherein each of R3, R4 and R2 are hydrogen, X and Y are both oxygen, and R1 is C1-6-alkyl, C2-6-alkenyl or C2-6-alkynyl, preferably methyl, ethyl, propyl or propargyl. 20. A pharmaceutical composition comprising a compound of any of Claim 1-19 together with a pharmaceutically acceptable carrier or diluent. 23. The use of a compound of any of Claim 1-20 for preparation of a pharmaceutical composition for treating cerebral ischaemia, Huntington's disease, epileptic disorders, Parkinson's disease, Alzheimer's disease, schizophrenia, pain, depression or anxiety, said method comprising.