Substituted (aminoiminomethyl or aminomethyl) benzoheteroaryl compounds
AssigneeAventis Pharmaceuticals Inc.
InventorsWilliam P. Dankulich, Daniel G. McGarry, Christopher Burns, Timothy F. Gallagher, Francis A. Volz
Life of this patent
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Abstract
This invention is directed to an (aminoiminomethyl or aminomethyl)benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.
Claims36
A compound of formula I:
- 18
- wherein
- X is O, S or NR1;
- R is hydrogen, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylcycloalkenyl, fused heteroarylcycloalkenyl, fused arylheterocyclyl, fused heteroarylheterocyclyl, fused arylheterocyclenyl, fused heteroarylheterocyclenyl, aryl, fused cycloalkenylaryl, fused cycloalkylaryl, fused heterocyclylaryl, fused heterocyclenylaryl, heteroaryl, fused cycloalkylheteroaryl, fused cycloalkenylheteroaryl, fused heterocyclenylheteroaryl or fused heterocyclylheteroaryl, provided that where L2 is a chemical bond then Q is attached to R through a carbon atom thereof or where R is hydrogen then L2 is not a chemical bond;
- R1 is hydrogen, alkyl, aralkyl, heteroaralkyl, acyl, aroyl, heteroaroyl, alkoxycarbonyl, aryloxycarbonyl or heteroaryloxycarbonyl;
- R2 and R3 are hydrogen, or taken together are ═NR4;
- R4 is hydrogen, R5O2C—, R5O—, HO—, cyano, R5CO—, HCO—, lower alkyl, nitro, or R6R7N—;
- R5 is alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl;
- R6 and R7 are independently hydrogen or alkyl;
- L1 is alkylene, alkenylene or alkynylene;
- L2 is a chemical bond, alkylene, alkenylene or alkynylene;
- Q is —NR8′, —O—, —C(O)—, —C(O)—O—, —O—C(O)—, —NR8′C(X1)—, —C(X1)NR8′—, —NR8C(X1)O—, —OC(X1)NR8—, —NR8C(X1)NR8—, —NR8C(X1)NR8—, —S(O)n—, —NR8SO2— or —SO2NR8—, provided that a nitrogen atom or oxygen atom of Q is not directly bonded to a carbon atom of L1 or L2 having a double bond or triple bond, or Q-L2-R is cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylcycloalkenyl, fused heteroarylcycloalkenyl, fused arylheterocyclyl, fused heteroarylheterocyclyl, fused arylheterocyclenyl, fused heteroarylheterocyclenyl, aryl, fused cycloalkenylaryl, fused cycloalkylaryl, fused heterocyclylaryl, fused heterocyclenylaryl, heteroaryl, fused cycloalkylheteroaryl, fused cycloalkenylheteroaryl, fused heterocyclenylheteroaryl or fused heterocyclylheteroaryl, provided that a nitrogen atom or oxygen atom of Q is not directly bonded to a carbon atom of L1 having a double bond or triple bond;
- X1 is O or S;
- R8′ is hydrogen, alkyl, aralkyl, heteroaralkyl, acyl, aroyl, heteroaroyl or alkoxycarbonyl;
- R8 is hydrogen, alkyl, aralkyl, heteroaralkyl, acyl, aroyl or heteroaroyl;
- and
- n is 0, 1 or 2, or
- an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof.
Dependencies are inferred from the claim text.