- PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
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This disclosure provides pharmaceutical compounds to treat medical disorders, such as complement-mediated disorders, including complement Cl -mediated disorders.
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- 1-substituted 4-arylpiperazine as kappa opioid receptor antagonists
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Provided are compounds represented by the formula: where R, Y3, R1, R2, R3, R4, R6, G, R7, E1, E2, A, B, W, X, Y and Z are as defined herein.
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Page/Page column 17-19
(2016/12/26)
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- Modulators of methyl modifying enzymes, compositions and uses thereof
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Page/Page column 144; 145
(2015/12/26)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
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Paragraph 00276; 00279
(2013/06/05)
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- Discovery of N-{4-[(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2- methylpropyl}-4-phenoxybenzamide analogues as selective kappa opioid receptor antagonists
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There is continuing interest in the discovery and development of new κ opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [35S] GTPγS binding assay showed that neither compound showed the high potency and κ opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [35S]GTPγS binding stimulated by the selective κ opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3- methylpiperazin-1-yl]methyl}-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good κ opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [35S]GTPγS binding assay showed that several of the analogues were potent and selective κ opioid receptor antagonists.
- Kormos, Chad M.,Jin, Chunyang,Cueva, Juan Pablo,Runyon, Scott P.,Thomas, James B.,Brieaddy, Lawrence E.,Mascarella, S. Wayne,Navarro, Hernán A.,Gilmour, Brian P.,Carroll, F. Ivy
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p. 4551 - 4567
(2013/07/19)
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- 1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS
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Provided are compounds represented by the formula: where R, Y3, R1,R2, R3, R4, R6, G, R7, E1, E2, A, B, W, X, Y and Z are as defined herein.
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Page/Page column 22; 23
(2013/06/27)
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- Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist
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S1P3-sparing S1P1 agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC50 value of 4.0 nM for human S1P1 and over 5000-fold selectivity against S1P3. The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID 50 value was determined at 0.407 mg/kg. The docking studies of CS-2100 with the homology model of S1P1 and S1P3 showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P3, not in the case of Leu276 in S1P1. This observation gives an explanation for the excellent S1P3-sparing characteristic of CS-2100.
- Nakamura, Tsuyoshi,Asano, Masayoshi,Sekiguchi, Yukiko,Mizuno, Yumiko,Tamaki, Kazuhiko,Kimura, Takako,Nara, Futoshi,Kawase, Yumi,Shimozato, Takaichi,Doi, Hiromi,Kagari, Takashi,Tomisato, Wataru,Inoue, Ryotaku,Nagasaki, Miyuki,Yuita, Hiroshi,Oguchi-Oshima, Keiko,Kaneko, Reina,Watanabe, Nobuaki,Abe, Yasuyuki,Nishi, Takahide
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p. 1788 - 1792
(2012/04/04)
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- DIACYLETHYLENEDIAMINE COMPOUND
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[Problem] A compound which is useful as an anti-obesity agent is provided. [Means for Solution] The present inventors have investigated a compound having a DGAT1 inhibitory action, which is promising as an active ingredient of a pharmaceutical composition
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Page/Page column 20; 53; 158
(2012/03/10)
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