- 5-[3-[PIPERIDIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS
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The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
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Paragraph 0260; 0261
(2018/01/15)
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- 5-[3-[PIPERAZIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS
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The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
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Paragraph 0282
(2018/01/15)
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- Discovery of a novel acyl-CoA: Cholesterol acyltransferase inhibitor: The synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety
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As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine) acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl) phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.
- Ogino, Masaki,Nakada, Yoshihisa,Negoro, Nobuyuki,Itokawa, Shigekazu,Nishimura, Satoshi,Sanada, Tsukasa,Satomi, Tomoko,Kita, Shunbun,Kubo, Kazuki,Marui, Shogo
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experimental part
p. 1369 - 1375
(2012/01/02)
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- 1-PHENYL 1-THIO-D-GLUCITOL DERIVATIVE
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A 1-phenyl 1-thio-D-glucitol compound represented by formula (I) or the like: or a pharmaceutically acceptable salt thereof or a hydrate thereof, or a pharmaceutical preparation comprising the same as an active ingredient is useful as a novel type of prophylactic or therapeutic agent for diabetes, diabetes-related diseases or diabetic complications, which inhibits both SGLT1 and SGLT2 activities to achieve not only suppression of glucose absorption from the digestive tract but also excretion of urinary sugars.
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Page/Page column 16
(2009/10/01)
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