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US 7,115,596 B2Granted
Thiazole compounds as integrin receptor antagonists derivatives
AssigneePharmacia Corporation
InventorsJohn A. Wendt, Heather Stenmark, Hongwei Wu, Yaping Wang, Barbara B. Chen, Thomas D. Penning, Victoria L. Downs, Mark L. Boys, Mark Russell, Dale P. Spangler
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Abstract
The present invention relates to a class of compounds represented by the Formula I or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of the Formula I, and methods of selectively inhibiting or antagonizing the αvβ3 and/or the αvβ5 integrin without significantly inhibiting the αvβ6 integrin.
Claims6
A compound corresponding to Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is selected from the group consisting of —CH(R2)—, —N(R3)—, —O—, —S—, —S(O)2—, and —C(O)—;
- Z1 is selected from the group consisting of hydrogen, heteroaryl, and optionally substituted alkyl or aryl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2—, sulfonamido, aryl, and heteroaryl;
- X1 is a carbon chain of 1 to 3 carbon atoms with or without a carbon-carbon unsaturated bond;
- X1 is selected from the group consisting of —O—, —S—, —SO—, —SO2—, —N—, and —CH2—;
- R2 is H, hydroxy, or alkoxy;
- R3 is selected from the group consisting of hydrogen, heteroaryl, optionally substituted alkyl or aryl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2, sulfonamido, aryl, and heteroaryl;
- R4 is carbon or nitrogen;
- R5 is selected from the group consisting of hydrogen, heteroaryl, and optionally substituted alkyl or aryl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2, sulfonamido, aryl, and heteroaryl;
- R6 is selected from the group consisting of hydrogen, heteroaryl, an electron pair, and optionally substituted alkyl or aryl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2, sulfonamido, aryl, and heteroaryl;
- R7 is hydroxy or alkoxy;
- X3 is selected from the group consisting of:
- wherein:
- X4 is selected from the group consisting of hydrogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyclicamino, heterocyclo, —N—SO2Rx wherein Rx is alkyl or aryl, and optionally substituted hydrocarbyl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2—, sulfonamido, aryl, and heteroaryl;
- X5, X6, and X8 are independently selected from the group consisting of hydrogen, heterocyclo, and optionally substituted hydrocarbyl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2—, sulfonamido, aryl, and heteroaryl;
- X7 is selected from the group consisting of —CH2, —CH2O—, —OCH2— —S—, —SO—, —SO2—, —O—, —C(O)—, —CH(OH)—, —NH—, and —NX8;
- and
- X9 is ═O or —OH.
15 more elements
A compound corresponding to Formula II:
- or a pharmaceutically acceptable salt thereof, wherein:
- n is 1–3;
- R10 is selected from the group consisting of aryl, aralkyl, heteroaralkyl, and heteroaryl;
- X3 is selected from the group consisting of:
- X4is hydrogen, hydroxy, alkoxy, amino, heterocyclo, and optionally substituted hydrocarbyl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2—, sulfonamido, aryl, and heteroaryl;
- X5, X6, and X8 are independently hydrogen, heterocyclo, or optionally substituted hydrocarbyl, wherein the substituent is selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, cyano, acyl, —S—, —SO—, —SO2—, sulfonamido, aryl, and heteroaryl;
- and
- X7 is —CH2, —CH2O—, —OCH2— —S—, —O—, —C(O)—, —CH(OH)—, —NH—, or —NX8.
5 more elements
Dependencies are inferred from the claim text.