Patent IL-129706-A (IL)
Title: HETEROCYCLIC DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, PROCESSES FOR THE PREPARATION OF SUCH DERIVATIVES AND USE THEREOF IN THE PREPARATION OF MEDICAMENTS FOR USE IN PRODUCING A FACTOR Xa INHIBITING EFFECT
IPC: A61K31/506
Filed: 1997-11-04
Abstract: A compound of the formula A-B-X1-T1(R2)-L1-T2(R3)-X2-Q wherein: A is 5- or 6-membered monocyclic aromatic ring contaiing 1, 2 or 3 ring heteroatoms selected from nitrogen, oxygen and sulphur atoms optionally substituted by one, two or three atoms or groups selected from halo, oxo, carboxy, trifluoromethyl, cyano, amino, hydroxy, nitro, C1-4 alkyl (for example methyl or ethyl), C1-4 alkoxy (for example methoxy or ethoxy), C1-4 alkoxycarbonyl, C1-4 alkylamino (for example methylamino or ethylamino) or di-C1-4 alkyamino (for example dimethylamino or diethylamino); B is a phenylene ring optionally substituted by one or two substituents selected from (a) halo, trifluoromethyl, trifluoromethoxy, 2627 י" ב בתשרי התשס" ה - September 27, 2004 cyano, nitro, C1-4 alkyl, C2-4 alkenyl and C2-4 alkynyl, (b) a substituent -(CH2)n Y1 wherein n is 0-4 and Y1 is selected from hydroxy, amino C1-4 alkoxy, C2-4 alkenyloxy, C2-4 alkynyloxy, C1-4 alkylamino, di-C1-4 alkylamino, pyrrolidin-1-yl, piperidino, morpholino, thiomorpholino, 1-oxothiomorpholino, 1,1-dioxothiomorpholino, piperazin-1-yl, 4-C1-4 alkylpiperazin-1-yl, C1-4 alkylthio, C1-4 alkylsulphinyl, C1-4 alkylsulphonyl, C2-4 alkanoylamino, benzamido, C1-4 alkylsulphonamido and phenylsulphonamido, (c) a substituent -(CH2)nY2 wherein n is 0-4 and Y2 is selected from carboxy, carbamoyl, C1-4 alkoxycarbonyl, N-C1-4 alkylcarbamoyl, N,N-di-C1-4 alkylcarbamoyl, pyrrolidin-1-ylcarbonyl, piperidinocarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, 1-oxothiomorpholinocarbonyl, 1,1-dioxothiomorpholinocarbonyl, piperazin-1-ylcarbonyl, 4-C1-4 alkylpiperazin-1-ylcarbonyl, C1-4 alkylsulphonamidocarbonyl, phenylsulphonamidocarbonyl and benzylsulphonamidocarbonyl, or (d) a substituent of the formula -X3-L2-Y2 wherein X3 is a group of the formula CON(R5), CON(L2-Y2), C(R5)2O, O, N(R5) or N(L2-Y2), L2 is C1-4 alkylene, Y2 has any of the meanings defined immediately hereinbefore and each R5 is independently hydrogen or C1-4 alkyl, and from a substituent of the formula -X3-L3-Y1 wherein X3 is a group of the formula CON(R5), CON(L3-Y1), C(R5)2O, O, N(R5) or N(L3-Y1), L3 is C2-4 alkylene, Y1 has any of the meanings defined immediately hereinbefore and each R5 is independently hydrogen or C1-4 alkyl, and wherein any heterocyclic group in a substituent of B optionally bears 1 or 2 substituents selected from carboxy, carbamoyl, C1-4 alkyl, C1-4 alkoxycarbonyl, N-C1-4 alkylcarbamoyl and N,N-diC1-4 alkylcarbamoyl, and wherein any phenyl group in a substituent of B optionally bears 1 or 2 substituents selected from halo, trifluoromethyl, cyano, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C2-4 alkenyloxy and C2-4 alkynyloxy; X1 is SO, SO2, C(R4)2 or CO when T1 is CH or N; or in addition X1 is O or S when T1 is CH; and wherein each R4 is independently hydrogen or C1-4 alkyl; T1 is CH or N, and T2 is CH or N with the proviso that at least one of T1 and T2 is N; 2628 י" ב בתשרי התשס" ה - September 27, 2004 L1 is C1-4 alkylene or C1-3 alkylenecarbonyl; R2 is hydrogen or C1-4 alkyl; R3 is hydrogen or C1-4 alkyl; or R2 and R3 are joined to form a C1-4 alkylene or -CH2CO- group; wherein the ring formed by T1, T2, L1, R2 and R3 is optionally substituted by one or two substituents selected from hydroxy, oxo, carboxy and C1-4 alkoxycarbonyl; or one of the following: -(CH2)n-R, -(CH2)n-NRR1, -CO-R, -CO- NRR1, -(CH2)n-CO-R and -(CH2)n-CO- NRR1; wherein n is 0, 1 or 2, preferably n is 1 or 2; R and R1 are independently selected from hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, hydroxy C1-4 alkyl, carboxy C1-4 alkyl and C1-4 alkoxycarbonyl C1-4 alkyl or where possible R and R1 may together form a 5- or 6-membered optionally substituted saturated or partially unsaturated (preferably saturated) heterocyclic ring which may include in addition to the nitrogen to which R and R1 are attached 1 or 2 additional heteroatoms selected from nitrogen, oxygen and sulphur, with the further proviso that when