- THIADIAZOLE MODULATORS OF S1P AND METHODS OF MAKING AND USING
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The invention is directed to compounds of the formula: wherein each of the variables are defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance treating an autoimmune disease.
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Paragraph 0219
(2017/01/26)
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- OXADIAZOLE MODULATORS OF S1P METHODS OF MAKING AND USING
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The invention is directed to Compounds of Formula (I): wherein each variable is defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance for treating graft versus host disease and autoimmune diseases.
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Paragraph 0142
(2017/01/23)
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- Treatment of estrogen-dependent diseases: Design, synthesis and profiling of a selective 17β-HSD1 inhibitor with sub-nanomolar IC50for a proof-of-principle study
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Current endocrine therapeutics for the estrogen-dependent disease endometriosis often lead to considerable side-effects as they act by reducing estrogen action systemically. A more recent approach takes advantage of the fact that the weak estrogen estrone (E1) which is abundant in the plasma, is activated in the target cell to the highly estrogenic estradiol (E2) by 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). 17β-HSD1 is overexpressed in endometriosis and thus a promising target for the treatment of this disease, with the prospect of less target-associated side-effects. Potent inhibitors from the class of bicyclic substituted hydroxyphenylmethanones with sulfonamide moiety recently described by us suffered from high molecular weight and low selectivity over 17βHSD2, the physiological adversary of 17β-HSD1. We describe the structural optimizations leading to the discovery of (5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl)(2,6-difluoro-3-hydroxyphenyl)methanone 20, which displayed a sub-nanomolar IC50towards 17β-HSD1 as well as high selectivity over the type 2 enzyme, the estrogen receptors α and β and a range of hepatic CYP enzymes. The compound did neither show cellular toxicity, nor PXR activation nor mutagenicity in the AMES II assay. Additional favourable pharmacokinetic properties (rat) make 20 a suitable candidate for proof-of-principle studies using xenotransplanted immunodeficient rats.
- Abdelsamie, Ahmed S.,van Koppen, Chris J.,Bey, Emmanuel,Salah, Mohamed,B?rger, Carsten,Siebenbürger, Lorenz,Laschke, Matthias W.,Menger, Michael D.,Frotscher, Martin
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p. 944 - 957
(2017/02/18)
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- Non-nucleoside reverse transcriptase inhibitors
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The present invention provides for compounds useful for treating an HIV infection, or preventing an HIV infection, or treating AIDS or ARC. The compounds of the invention are of formula I wherein R1, R2, R3, R4, R5a, R5b, R6a, R6b and X are as herein defined. Also disclosed in the present invention are methods of treating an HIV infection with compounds defined herein and pharmaceutical compositions containing said compounds.
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Page/Page column 24
(2008/12/06)
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- A REGIOSPECIFIC SYNTHESIS OF CARBAZOLES VIA CONSECUTIVE PALLADIUM-CATALYZED CROSS-COUPLING AND ARYNE-MEDIATED CYCLIZATION
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A regiospecific synthesis of carbazoles has been developed using palladium-catalyzed cross-coupling of N-(tert-butoxycarbonyl)-2-tributylstannylanilines with 2- or 3-bromochlorobenzene followed by aryne-mediated cyclization as the key reactions.The carbazole alkaloids, glycozolinine and glycozolidine, were synthesized using this procedure.
- Iwao, Masatomo,Takehara, Hirokazu,Furukawa, Sunao,Watanabe, Mitsuaki
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p. 1483 - 1488
(2007/10/02)
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