- INHIBITING HUMAN INTEGRIN α4β7
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Disclosed are small molecule antagonists of human α4β7 integrin, and methods of using them to treat a number of diseases and conditions.
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- Synthesis of (±)-14-epi-hydroxydolasta-1(15),7,9-triene and (±)-7-epi -acetoxy-14-epi-hydroxydolasta-1(15),8-diene
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1,3-Dimethyl-2-nitrobenzene was converted to the key intramolecular Friedel-Crafts intermediate 24 in ten steps. Treatment of 24 with TiCl 4 produced tricyclic enone 25 in 61%-75% yield, having the requisite trans relationship of the two angular methyl groups and many of the salient features of the dolastane diterpenes. The structure of enone 25 was verified by X-ray crystallography analysis. Cyclization product 25 permitted the facile synthesis of (±)-14-epi-hydroxydolasta-1(15),7,9-triene and (±)-7-epi-acetoxy-14-epi-hydroxydolasta-1(15),8-diene, which are detailed in this article.
- Majetich, George,Yu, Jianhua
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- 3-ARYL-5,6-DISUBSTITUTED PYRIDAZINES
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The present invention provides compounds of Formula (I) or (II) salt form or prodrug thereof, wherein variables are defined herein, that are modulators of metalloproteases such as matrix metalloproteases (MMPs) and ADAMs. The compounds or compositions described herein can be used to treat diseases associated with metalloprotease activity including, for example, arthritis, cancer, cardiovascular disorders, skin disorders, inflammation or allergic conditions.
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Page/Page column 51-52
(2010/02/15)
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- 4,5-DISUBSTITUTED-2-ARYL PYRIMIDINES
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4,5-disubstituted-2-arylpyrimidines of Formula (I) and Formula (II) are provided: wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula I and II bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 4,5-disubstituted-2-arylpyrimidines, which are useful as probes for the localization of C5a receptors.
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- 1-ARYL-4-SUBSTITUTED ISOQUINOLINES
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1-Aryl-4-substituted isoquinolines analogues of Formula (I) and Formula (II) are provided, as follows : wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) and (II) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 1-aryl-4-substituted isoquinolines, which are useful as probes for the localization of C5a receptors.
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- 3-SUBSTITUTED-6-ARYL PYRIDINES
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3-substituted-6-aryl pyridines of Formula (I) are provided: Formula (I) wherein R1, R2, R3, R8, R9, A and Ar are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of Formula (I) bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. The present invention also relates to pharmaceutical compositions comprising such compounds, and to the use of such compounds in treating a variety of inflammatory, cardiovascular, and immune system disorders. In addition, the present invention provides labeled 3-substituted-6-aryl pyridines, which are useful as probes for the localization of C5a receptors.
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