- 1-(HET)ARYLSULFONYL-(PYRROLIDINE OR PIPERIDINE)-2-CARBOXAMIDE DERIVATIVES AND THEIR USE AS TRPA1 ANTAGONISTS
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The invention is concerned with the compounds of formula I and salts thereof and other compounds of formulas II-IX as disclosed herein. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formulas I-IX as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain or asthma.
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Paragraph 01470; 01471; 01472
(2016/09/22)
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- Hydroxyalkyl cyclic diamine compound
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The present invention is directed to a compound represented by the following formula (1) and to a process for producing a compound (5) from the compound (1). By use of the compound (1) of the present invention, a variety of cyclic diamine derivatives (5) or salts thereof, useful as drugs, can be produced in an industrially advantageous manner with a constant yield.
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- Compounds and methods which modulate feeding behavior and related diseases
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There are provided compounds, compositions and methods of use thereof in the modulation of feeding behavior, obesity, diabetes, cancer (tumor), inflammatory disorders, depression, stress related disorders, Alzheimer's disease and other disease conditions.
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- Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists
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Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3,2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.
- Norman,Chen,Chen,Fotsch,Hale,Han,Hurt,Jenkins,Kincaid,Liu,Lu,Moreno,Santora,Sonnenberg,Karbon
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p. 4288 - 4312
(2007/10/03)
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- Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 3. Discovery of a novel series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas with weak toxicological effects on adrenal glands
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A series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas were prepared and evaluated for their ability to inhibit intestinal acyl-CoA:cholesterol O- acyltransferase and to inhibit accumulation of cholesteryl esters in macrophages in vitro. In vivo hypocholesterolemic activity was assessed in cholesterol-fed rats by oral administration as a dietary admixture and/or by gavage in a PEG400 vehicle. Modification of the alkyl substituent on the N'- aryl moiety and on the urea nitrogen significantly influenced macrophage assay in vitro. Toxicological study revealed a distinct relationship between macrophage assay and the toxicity observed in adrenal glands of rabbits treated with representatives of this series of compounds. Investigations utilizing the macrophage assay as an indicator for adrenal toxicity led to the identification of compounds 1g (FR190809) and 1k (FR186485, or FR195249 as its hydrochloride salt) as potent, nonadrenotoxic, orally efficacious ACAT inhibitors irrespective of the administration method.
- Tanaka, Akira,Terasawa, Takeshi,Hagihara, Hiroyuki,Ishibe, Noriko,Sawada, Masae,Sakuma, Yuri,Hashimoto, Masaharu,Takasugi, Hisashi,Tanaka, Hirokazu
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p. 4408 - 4420
(2007/10/03)
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