- NOVEL COMPOUNDS
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Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 62
(2015/12/17)
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- MIXTURES OF ITACONIC ACID OR ITACONIC ACID DERIVATIVES AND PRIMARY AMINES FOR PRODUCING 1,3- AND 1,4-ALKYL METHYL PYRROLIDONES
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The present invention relates to a mixture comprising itaconic acid or an itaconic acid derivative and a primary amine of the formula (I) [in-line-formulae]R—NH2??(I)[/in-line-formulae] where the molar ratio of primary amine to itaconic acid or the itaconic acid derivative is in the range from 0.5:1 to 20:1, wherein the mixture comprises 50 mole percent or less of 4-carboxypyrrolidones of the formula (II), derivatives of the 4-carboxypyrrolidones of the formula (II) and 4-carbamidopyrrolidones of the formula (III) based on the itaconic acid used or the itaconic acid derivative used and in which R is a linear or branched saturated aliphatic radical having 1 to 24 carbon atoms or a saturated cycloaliphatic radical having 3 to 24 carbon atoms. The invention further provides for the use of the inventive mixtures for preparing 1,3-alkylmethylpyrrolidones and/or 1,4-alkylmethylpyrrolidones, and also a process for preparing 1,3-alkylmethylpyrrolidones and/or 1,4-alkylmethylpyrrolidones. In addition, the present invention relates to mixtures comprising 1,3-alkylmethylpyrrolidones and/or 1,4-alkylmethylpyrrolidones and 1,3-alkylmethylpyrrolidines, where the proportion of 1,3-alkylmethylpyrrolidines is in the range from 10 to 10 000 ppm, and to mixtures comprising 1,3-alkylmethylpyrrolidone and 1,4-alkylmethylpyrrolidone, wherein the molar ratio of 1,3-alkylmethylpyrrolidone to 1,4-alkylmethylpyrrolidone is in the range from 1:1 to 10:1.
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Page/Page column 13
(2011/10/19)
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- CCR5 antagonists as anti-HIV-1 agents. 1. Synthesis and biological evaluation of 5-oxopyrrolidine-3-carboxamide derivatives
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A novel lead compound, N-{3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl}-1- methyl-5-oxo-N-phenylpyrrolidine-3-carboxamide (1), was identified as a CCR5 antagonist by high-throughput screening using [125I]RANTES and CCR5-expressing CHO cells. The IC50 value of 1 was 1.9 μM. In an effort to improve the binding affinity of 1, a series of 5-oxopyrrolidine-3- carboxamides was synthesized. Introduction of 3,4-dichloro substituents to the central phenyl ring (10i, IC50=0.057 μM; 11b, IC 50=0.050 μM) or replacing the 1-methyl group of the 5-oxopyrrolidine moiety with a 1-benzyl group (12e, IC50=0.038 μM) was found to be effective for improving CCR5 affinity. Compound 10i, 11b, and 12e also inhibited CCR5-using HIV-1 envelope-mediated membrane fusion with IC50 values of 0.44, 0.19, and 0.49 μM, respectively.
- Imamura, Shinichi,Ishihara, Yuji,Hattori, Taeko,Kurasawa, Osamu,Matsushita, Yoshihiro,Sugihara, Yoshihiro,Kanzaki, Naoyuki,Iizawa, Yuji,Baba, Masanori,Hashiguchi, Shohei
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