- PYRAZOLE-CONTAINING MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS
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In one aspect, the invention comprises compounds that bind and inhibit macrophage migration inhibitory factor. In another aspect, the invention provides methods of treating inflammatory disease, neurological disorders and cancer using the compounds of the invention.
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Page/Page column 111; 112
(2019/10/04)
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- Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor
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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is implicated in the regulation of inflammation, cell proliferation, and neurological disorders. MIF is also an enzyme that functions as a keto–enol tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which hydrogen bonds to Asn97 in the active site. Starting from a 113-μm docking hit, we report results of structure-based and computer-aided design that have provided substituted pyrazoles as phenol alternatives with potencies of 60–70 nm. Crystal structures of complexes of MIF with the pyrazoles highlight the contributions of hydrogen bonding with Lys32 and Asn97, and aryl–aryl interactions with Tyr36, Tyr95, and Phe113 to the binding.
- Trivedi-Parmar, Vinay,Robertson, Michael J.,Cisneros, José A.,Krimmer, Stefan G.,Jorgensen, William L.
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supporting information
p. 1092 - 1097
(2018/04/30)
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- PHENYLALKYLCARBOXYLIC ACID DELIVERY AGENTS
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The present invention provides phenylalkylcarboxylic acid compounds and compositions containing such compounds which facilitate the delivery of biologically active agents.
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- 4,5-DIHYDRONAPHTHO [1,2-b] THIOPHENE DERIVATIVE
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A 4,5-dihydronaphtho[1,2-b]thiophene derivative expressed by the formula: (wherein R1 is a C1 to C10 1-hydroxyalkyl group or a C1 to C10 acyl group, and R2 and R3 separately substitute in the 6-, 7-, 8-, or 9-positions, and are each independently a hydrogen atom, a halogen atom, a C1 to C10 alkyl group, a hydroxy group, a C1 to C10 alkoxy group, a C1 to C5 alkenyloxy group, a C1 to C5 alkynyloxy group, a benzyloxy group, or the like, provided that when R1 is an acyl group and R2 is a hydrogen atom, then R3 is neither a hydrogen atom nor an acetyl group), or a pharmaceutically acceptable salt thereof. This is a novel compound that is effective in reducing triglyceride levels in the liver and reducing blood glucose levels.
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Page/Page column 12
(2010/11/08)
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- ARYL(ALKYL)PROPYLAMIDES
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The invention relates to a compound selected from those of formula (I) : STR1 in which A, R 1, R' 1, R 2, R 3 and n are as defined in the description, and medicinal product containing the same useful for treating a mammal afflicted with a disorder of the
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- TETRAHYDRO-1H-BENZAZEPINONES AND HEXAHYDROAZEPINONES AS SELECTIVE CHOLECYSTOKININ-B RECEPTOR ANTAGONISTS
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This invention relates to compounds of formula (I) wherein R. sup.1, R. sup.2, R 3, R 4 and X are as defined in the application. These compounds are CCK-B receptor antagonists and are useful in the treatment and prevention of central nervous system and gastrointestinal disorders. STR1
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- Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: Pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system
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A series of 4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives bearing substituents at the 2- and 6-positions were synthesized, and evaluated in vitro for their inhibitory activity on rabbit platelet aggregation induced by platelet activating factor (PAF) and in vivo for their preventing effect on PAF-induced mortality in mice. The length of alkyl or arylalkyl side chain at the 2-position was responsible for enhancing the affinity for the PAF receptor. The simultaneous substitution at both the 2- and 6-positions resulted in a successful separation of the affinity for the PAF receptor from that for the benzodiazepine (BZ) receptor. Thus, (±)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]- 6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4] diazepine (Y-24180) was confirmed to be a specific antagonist for the PAF receptor and is currently under clinical trials.
- Kawakami,Kitani,Yuasa,Abe,Moriwaki,Kagoshima,Terasawa,Tahara
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p. 683 - 692
(2007/10/03)
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- SCHWEFELVERBINDUNGEN DES ERDOELS XIII. 2,11-DIALKYLDINAPHTHO--THIOPHENE UND 2,12-DIALKYLDINAPHTHO-1,4-DITHIINE
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Starting with 7-alkyl-2-bromo-1,2,3,4-tetrahydronaphthalen-1-ones 1 2,11-dialkylnaphthothiophenes 9 and 2,12-dialkyldinaphtho-1,4-dithiines 8 are synthesized according to Scheme 2.The anellation on 9 is proved by nmr-data.
- Nink, Gunter,Boberg, Friedrich
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p. 227 - 233
(2007/10/02)
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