- Novel potent and selective Ca2+ release-activated Ca2+ (CRAC) channel inhibitors. Part 3: Synthesis and CRAC channel inhibitory activity of 4′-[(trifluoromethyl)pyrazol-1-yl]carboxanilides
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From a series of 4'-[(trifluoromethyl)pyrazol-1-yl]carboxanilides derived from 4-methyl-4'-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,3-thiadiazole-5-carboxanilide, one inhibited thapsigargin-induced Ca2+ influx in Jurkat T cells (IC50 = 77 nM) and exhibited high selectivity for the CRAC channel over the VOC channel (index: >130). Another acted as an inhibitor for both T lymphocyte activation-induced diseases and ovalbumin-induced airway eosinophilia in rats (ED50 = 1.3 mg/kg) p.o.
- Yonetoku, Yasuhiro,Kubota, Hirokazu,Miyazaki, Yoji,Okamoto, Yoshinori,Funatsu, Masashi,Yoshimura-Ishikawa, Noriko,Ishikawa, Jun,Yoshino, Taiji,Takeuchi, Makoto,Ohta, Mitsuaki
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experimental part
p. 9457 - 9466
(2009/04/07)
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- PREPARATION OF KETONE AMIDES
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The present invention discloses a novel process to prepare ketone amides, which are useful intermediates for the preparation of antagonists of CCR5 receptor and therefore useful for the treatment of HIV virus infected mammals. It specifically discloses a novel process to synthesize 1-(2,4-dimethylpyrimidine-5-carbonyl)-4-piperidone, 1-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4-piperidone and related compounds. A salient feature of the invention is the use of a three-phase reaction medium with an organic phase and a buffer salt slurry.
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Page/Page column 11-12
(2008/06/13)
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- PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDK' S AND GSK' S
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The invention provides compounds of the formula (I), or salts, tautomers, N-oxides or solvates thereof wherein: R1 is selected from: (a) 2,6-dichlorophenyl; (b) 2,6-difluorophenyl; (c) a 2,3,6-trisubstituted phenyl group wherein the substituents for the phenyl group are selected from fluorine, chlorine, methyl and methoxy; (d) a group R0; (e) a group R a; (f) a group Rlb; (g) a group Rlc; (h) a group Rld; and 0) 2,6-difluorophenylamino ; wherein R )0υ, r R> llaa, T Rj I1bD, T R) I1cC, r R> Iidα, r R?2zaa, r R>22bD and RJ are as defined in the claims. The compounds have activity as inhibitors of cdk kinase (such as cdkl or cdk2) and glycogen synthase kinase-3 activity.
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Page/Page column 196
(2008/06/13)
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- NAD(P)H-NAD(P)+ Models. 73. Structure-Stereochemistry Relationship in the Reaction of NAD Analog
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Four different NAD(P)H analogs have been oxidized by various substituted and unsubstituted 1,4-benzoquinones in the presence or absence of magnesium ion.The stereospecificity of the reaction depends not only on the reactivity of quinone but also on that of the analogs as well as on the presence or absence of magnesium ion.The results are discussed from the viewpoint of reaction mechanism for the transfer of a (net) hydride ion.
- Ohno, Atsuyoshi,Mikata, Yuji,Goto, Mutsuo,Kashiwagi, Takeshi,Tanaka, Takanori,Sawada, Masami
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