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US 7,465,798 B2Granted
Methods and compositions for selectin inhibition
AssigneeWyeth
InventorsNeelu Kaila, Silvano L. Debernardo, Kristin M. Jantz, Raymond T. Camphausen, Patricia W. Bedard, Adrian Huang
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Abstract
The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.
Claims35
A compound having the Formula III:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- bond a and bond b are each a single bond;
- k is 1;
- Q1, Q2, Q3 and Q are each CHR2;
- L is CO2H or an ester thereof;
- Y is O, (CR3R4)por NR5;
- n′ is 0 or 1;
- p is 1 to 3;
- X is OH, OR3, OC1-6 alkyl, OC(═O)-aryl, OC(═O)C1-6 alkyl OC(═O)OC1-6 alkyl, or NR3R3;
- each R1, R3, R3, and R4 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 perhaloalkyl OC1-6 alkyl, OC1-6 perhaloalkyl, halogen, thioalkyl, CN, OH, SH, (CH2)nOSO3H, (CH2)nSO3H, (CH2)nCO2R6, OSO3R6, SO3R6, PO3R6R7;
- each R12 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 perhaloalkyl, OC1-6 alkyl, OC1-6 perhaloalkyl, thioalkyl, OH, (CH2)1OSO3H, (CH2)1SO3H, (CH2)1CO2R6,(CH2)1SO2NR8R9, (CH2)1C(═O)NR8R9, NR8R9, alkenyl, alkynyl, or NHCOR8, wherein any of said alkyl, Oalkyl, alkenyl or alkynyl can optionally be substituted with up to three substituents selected from the group consisting of halogen, C1-6 alkyl, OC1-6 alkyl and CN;
- each n is an independently selected integer from 0 to 6;
- each 1 is an independently selected integer from 1 to 6;
- and
- Z is aryl, arylalkyl, heteroaryl or heterocyclo, wherein each of said aryl, arylalkyl, heteroaryl and heterocyclo is optionally substituted.
13 more elements
Dependencies are inferred from the claim text.