Patent FR-2808798-A1 (FR)
Title: New N-heterocyclyl-aminoacid derivatives and analogs, are vitronectin analogs useful e.g. for treating osteoporosis, tumor growth or metastasis, inflammation or cardiovascular disease
IPC: A61P9/00
Filed: 2000-05-09
Abstract: N-Heterocyclyl-aminoacid derivatives and analogs (I) are new. N-Heterocyclyl-amine derivatives of formula R1-Y-A-B-D-E-F'-G (I) and their isomers, isomer mixtures and salts are new.  R1  = R3-C(=NR2)-NR2-, R2R3N-C(=NR2)- or R2R3N-C(=NR2)-NR2-; or a mono- or polycyclic system (optionally substituted (os) by R10 - R13), in which each ring is 4-10 membered and aromatic or non-aromatic, and at least one ring contains 1-4 heteroatom(s) selected from N, O and S; Y  = direct bond or -N(R2)-;  A  = direct bond, alkylene, -NR2-C(O)-NR2-, -NR2-C(O)-O-, -NR2-C(O)-S-, -NR2-C(S)-NR2-, -NR2-C(S)-O-, -NR2-C(S)-S-, -NR2-S(O)n-NR2-, -NR2-S(O)n-O-, -NR2-S(O)n-, cycloalkylene, -CC-, -NR2-C(O)-, -C(O)-NR2-, -arylene-C(O)-NR2-, O, S(O)n, arylene, CO, -arylene-CO-, N(R2), SO2NR2, COO, -C(R2)=C(R3)-, -arylene-CO- or -arylene-S(O)n- (all os at either end by alkylene (no C-number specified));  B  = direct bond, alkylene, -C(R2)=C(R3)- or -CC- (all os at either end by alkylene (no C-number specified));  D, F'  = direct bond, alkylene, O, NR2, CONR2, -NR2-C(O)-, -NR2-C(O)-NR2-, -NR2-C(S)-NR2-, OC(O), C(O)O, CO, CS, SO2, SO2-NR2, -NR2-S(O)-, -NR2-S(O)2-, S, -C(R2)=C(R3)-, -CC- or -CH(OH)- (all os at either end by alkylene (no C-number specified));  E  = mono- or polycyclic system (os by R10 - R13), in which each ring is 4-10 membered and aromatic or non-aromatic, and contains 0-4 heteroatom(s) selected from N, O and S;  G  = -C(R4)(NHR5)-(CH2)q-R6;  q  = 0 or 1;  R2, R3  = H, alkyl (os by one or more halo), cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, NH2, R8O-N(R8)-R7-, R8O-R7-, R8O-C(O)-R7-, R8-aryl-R7-, N(R8)2-R7-, HO-alkyl-N(R8)-R7-, N(R8)2-C(O)R7-, R8C(O)-N(R2)-R7-, R8C(O)-R7-, N(R8)2-C(=NR8)-, N(R8)2-C(=NR8)-NR2-, (1-18C) alkylcarbonyloxy or (1-6C) alkoxycarbonyl;  R4  = H, F, alkyl, cycloalkylalkyl, aryl or arylalkyl (where alkyl is os by one or more F);  R5  = mono- or polycyclic system (os by R10 - R13), in which each ring is 4-10 membered and aromatic or non-aromatic, and at least one ring contains 1-4 heteroatom(s) selected from N, O and S;  R6  = C(O)R9, C(S)R9, S(O)nR9, P(O)(R9)n or a 4-8 membered heterocycle containing 1-4 heteroatom(s) selected from N, O and S (e.g. tetrazole, imidazole, pyrazole, oxazole or thiadiazole);  R7  = direct bond or alkylene;  R8  = H, alkyl, cycloalkylalkyl, aryl or arylalkyl (where alkyl is os by one or more F);  R9  = OH, alkoxy, arylalkoxy, aryloxy, alkylcarbonyloxy-(1-4C) alkoxy, arylalkylcarbonyloxy-(1-4C) alkoxy, NH2, mono- or dialkylamino, aralkylamino, dialkylaminocarbonylmethoxy, aryl-dialkylaminocarbonylmethoxy, arylamino or the residue of a D- or L-aminoacid;  R10-R13  = H, alkyl (os by one or more halo), cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, NH2, R8O-N(R8)-R7-, R8O-R7-, R8O-C(O)-R7-, R8-aryl-R7-, NR8R2-R7-, HO-alkyl-N(R2)-R7-, R2-N(R8)-C(O)R7-, R8C(O)-N(R2)-R7-, R8C(O)-R7-, R2 N(R3)-C(=NR2)-, R2-N(R3)-C(=NR2)-NR2-, =O, =S, halo, NO2, R8SO2-R7-, R8NHSO2-R7- or R8N(R2)SO2-R7-;  n  = 1 or 2;  unless specified otherwise alkyl or alkylene moieties have 1-8C, cycloalkyl or cycloalkylene moieties 3-8C and aryl or arylene moieties 5-14C. An Independent claim is included for the preparation of (I).