Monocyte chemoattractant protein-1 (MCP-1) is a major chemoattractant for monocytes and memory T cells by means of their binding to its specific cell-surface receptor, CC-chemokine receptor-2 (CCR2). CCR2 belongs to the G-protein-coupled seven-transmembrane receptor superfamily. The evidence in favor of CCR2 and MCP-1 having dominant roles in monocyte chemotaxis and chronic inflammation was provided by CCR2 and MCP-1 knockout mice. It has been recognized that CCR2 antagonists are potential therapeutic agents in preventing, treating, or ameliorating a CCR2-mediated inflammatory syndrome or disease such as psoriasis, uveitis, rheumatoid arthritis, multiple sclerosis, asthma, obesity, and chronic obstructive pulmonary disease. This review summarizes recent developments in small-molecule CCR2 antagonists disclosed by patent applications published between 2005 and 2008 and related publications.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Treatment of (benzothiazol-2-yl)acetone oxime 1 with excess trifluoroacetic anhydride (TFAA) at room temperature produces 2-methyl-3-trifluoroacetylpyrazoIo[5, l-Z>]benzothiazole 11 in 71-92 % yield depending on the purity of the oxime.Compound 11 is reduced by NaBHi to the corresponding alcohol 12 and hydrolyzed to the corresponding carboxylic acid 13 under alkaline conditions.Other reagents commonly used to promote Beckmann rearrangement of oximes cause only decomposition of 1 to intractable materials.
An approach to many-membered ring N,S-heterocycles involving sulfoxide electrophilic sulfenylation (SES) followed by ring expansion of the derived sulfonium salt intermediate (in situ) is illustrated for 9- and 10-membered-ring compounds. Treatment of readily prepared sulfoxides 10a, 10b, 18a, 18b, 23a, and 23b with triflic anhydride (pyridine, CH2Cl2, 0 °C) provides heterocycles 13a (65%), 13b (60%), 19a (67%), 19b (67%), 24a (42%), and 24b (80%), respectively. Sulfoxides 5a and 5b, under several different conditions, give only the Pummerer dehydration products 6a and 6b, respectively. Diastereomeric sulfoxides 18a' and 18b', upon treatment with triflic anhydride, do not produce clean product mixtures or any of the desired heterocyclic products but, upon heating in toluene, are converted to the more stable isomers 18a and 18b, respectively. Conducting this isomerization in the presence of 2-mercaptobenzothiazole produces a disulfide indicative of the intermediacy of a sulfenic acid. However, the importance of sulfenic acid derivatives in the SES process leading to many-membered ring heterocycles remains to be determined.
Abstract The tert -butyl ester of 3-methoxy-2-pyrrolecarboxylic acid 3 undergoes reaction with singlet oxygen to form an intermediate imino hydroperoxide 4 . This hydroperoxide may be trapped by a variety of nucleophiles yielding 5-substituted pyrroles 6 . With strong nucleophilic substituents at the 5-position, these pyrroles may add to unreacted hydroperoxide 4 to form bipyrrole-like products 7 .
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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