- Structure-based design, synthesis, and antimicrobial activity of purine derived SAH/MTA nucleosidase inhibitors
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The structure-based design, synthesis, and biological activity of novel inhibitors of S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Using 6-substituted purine and deaza purines as the core scaffolds, a systematic and structure guided series of modifications provided low nM inhibitors with broad-spectrum antimicrobial activity.
- Tedder, Martina E.,Nie, Zhe,Margosiak, Stephen,Chu, Shaosong,Feher, Victoria A.,Almassy, Robert,Appelt, Krzysztof,Yager, Kraig M.
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p. 3165 - 3168
(2007/10/03)
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- 2,4,5,-trisubstituted pyrimidine derivatives
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The invention relates to compounds of the formula wherein R1 is lower alkyl, lower alkoxy, pyridinyl, pyrimidinyl, phenyl, —S-lower alkyl, —S(O)2-lower alkyl, —N(R)—(CH2)n—N(R)2, —O—(CH2)n—N(R)2, —N(R)2, or a cyclic tertiary amine of the group which may contain one additional heteroatom, selected from N, O or S, and wherein this group may be connected with the pyrimidine ring via the linker —O(CH2)n—; R2 is hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R3/R3′ is, independently from each other, hydrogen or lower alkyl; R4 is independently from each other halogen, trifluoromethyl or lower alkoxy; R5 is hydrogen or lower alkyl; R is, independently from each other, hydrogen or lower alkyl; X is —C(O)N(R)— or —N(R)C(O)—; Y is —O—, —S—, —SO2—, - or —N(R)—; n is 1,2,3 or 4; and m is 0,1 or 2; or a pharmaceutically acceptable acid addition salt thereof. The compound of the invention has affintity to the NK1 receptor and is therefore suitable in the treatment of diseases related to this recepor.
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- Novel inhibitors of AP-1 and NF-κB mediated gene expression: Structure-activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carb oxylate
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In an effort to identify novel inhibitors of AP-1 and NF-κB mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carb oxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (11) was identified as the most potent in this series. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Palanki, Moorthy S.S.,Erdman, Paul E.,Manning, Anthony M.,Ow, Arnold,Ransone, Lynn J.,Spooner, Cheryl,Suto, Carla,Suto, Mark
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p. 1645 - 1648
(2007/10/03)
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