- Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists
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Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.
- Kiyoi, Takao,York, Mark,Francis, Stuart,Edwards, Darren,Walker, Glenn,Houghton, Andrea K.,Cottney, Jean E.,Baker, James,Adam, Julia M.
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scheme or table
p. 4918 - 4921
(2010/11/04)
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- PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS
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GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure formula (I) wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
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- PYRIMIDINE-2, 4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS
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GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
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- TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS
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The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alky
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- Asymmetric synthesis of 1,2-amino alcohols using tert-butanesulfinimines as chiral auxiliary
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Facile and highly stereoselective synthesis of 1,2-amino alcohols has been achieved by the addition of [(dimethylphenyl-silyl)methyl] magnesium chloride to the tert-butanesulfinimines, followed by Fleming-Tamao oxidation of the silicon moiety.
- Ko, Chang Hong,Jung, Doo Young,Kim, Min Kyun,Kim, Yong Hae
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p. 304 - 308
(2007/10/03)
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- 3-(2-Aminoalkyl)-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl) -6-methyluracils as orally bioavailable antagonists of the human gonadotropin releasing hormone receptor
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Uracils possessing N-3 side chains derived from various amino alcohols were designed and synthesized as potent human gonadotropin releasing hormone receptor antagonists. The compounds herein presented displayed superior metabolic stability than their pred
- Tucci, Fabio C.,Zhu, Yun-Fei,Guo, Zhiqiang,Gross, Timothy D.,Connors Jr., Patrick J.,Gao, Yinghong,Rowbottom, Martin W.,Struthers, R. Scott,Reinhart, Greg J.,Xie, Qiu,Chen, Ta Kung,Bozigian, Haig,Bonneville, Anne L. Killam,Fisher, Andrew,Jin, Liping,Saunders, John,Chen, Chen
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p. 3483 - 3486
(2007/10/03)
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- 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2
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Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allow
- Sheppard, George S.,Wang, Jieyi,Kawai, Megumi,BaMaung, Nwe Y.,Craig, Richard A.,Erickson, Scott A.,Lynch, Linda,Patel, Jyoti,Yang, Fan,Searle, Xenia B.,Lou, Pingping,Park, Chang,Kim, Ki H.,Henkin, Jack,Lesniewski, Richard
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p. 865 - 868
(2007/10/03)
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- Chiral electrophilic 'glycinal' equivalents. New synthons for optically active α-amino acids and 4-substituted 2-oxazolidinones
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The thermal reaction of 3-[(1S)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones (21a-c) with dialkyl azodicarboxylates (9) results in exclusive formation of [4 + 2] type cycloadducts (22 and 23) with moderate levels of diastereofacial selection (up to 72% d.e.). The diastereomers thus obtained were readily purified and subsequent treatment with acidic methanol followed by removal of the auxiliary with LiBH4/MeOH (1:2) gave optically pure 4-methoxy-5-hydrazino-2-oxazolidinones (26 and 27), which serve as α-aminoaldehyde templates useful for the synthesis of a wide variety of optically active α-amino acids as well as 4-alkyl and 4-aryl-2-oxazolidinones.
- Matsunaga, Hirofumi,Ishizuka, Tadao,Kunieda, Takehisa
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p. 1275 - 1294
(2007/10/03)
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