Orally-active nipecotamide glycolamide esters for the treatment of thrombosis disorders

A compound represented by the general formula (I):

• wherein M is CH═CH or C≡C;
• A is selected from any of piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl,
• NHR2 or
• wherein R9 is selected from any of H, alkyl, CH(NH), CMe(NH) or acyl;
• R10 is H or C(O)N(R1)YZ,
• wherein R1 is selected from H or cycloalkyl;
• R2 is selected from any of H, alkyl or acyl;
• R5 is H or C(O)NHQ(CHW)rCO2R8;
• wherein Q is selected from CH-heteroaryl, or CH-substituted-heteroaryl, wherein the heteroaryl is selected from pyridyl, thienyl, furanyl or quinolinyl;
• W is selected from H or N(R6)T—R7;
• wherein R6 is selected from any of H, alkyl or acyl;
• T is selected from C(O), C(N—CN) or SO2;
• R7 is selected from any of alkyl, aryl, aralkyl, alkoxy, or aminoalkyl;
• and R8 is H or CH2C(O)NR11R12, wherein R11 and R12 are selected from H, alkyl, or cycloalkyl;
• m is the integer 1, 2, or 3;
• X is selected from any of C(O), C(O)O, C(O)NH, CH2, or SO2;
• n is the integer 1, 2, or 3;
• r is 0 or 1;
• Y is selected from any of (CH2)p, CH(R3)(CH2)q, (CH2)qCH(R3), (CH(CO2R4)CH2)q, (CH2)qCHOH or piperidine-3-carboxylic acid;
• with the proviso that when Y is (CH2)p and p is 2, X is other than C(O) or when X is C(O) then either R1 is other than H or R2 is other than H, and with the proviso that when Y is (CH(CO2R4)CH2)q X is other than C(O) or CH2;
• p is 2or3;
• q is 1, 2, or 3;
• R3 is alkyl, C2-C8 alkenyl, C2-C8 alkynyl, aryl, aralkyl or heteroaryl;
• R4 is H or alkyl or cycloalkyl;
• Z is CO2CH2C(O)NR11R12;
• provided that at least one of R5 and R10 is hydrogen and R5 and R10 are not hydrogen at the same time;
• provided that when R5 is C(O)NHQ(CHW)rCO2R8 and Q is CH-heteroaryl or CH-substituted-heteroaryl, and R8 is H, then M is CH═CH;
• or the enantiomer or the pharmaceutically acceptable salt thereof.