- Regioselective synthesis of sterically encumbered diaryl ethers based on one-pot cyclizations of 4-aryloxy-1,3-bis(trimethylsilyloxy)-1,3-dienes
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Sterically encumbered diaryl ethers are prepared based on formal [3+3] cyclizations of novel 4-aryloxy-1,3-bis(trimethylsilyloxy)-1,3-dienes.
- Rashid, Muhammad A.,Rasool, Nasir,Adeel, Muhammad,Reinke, Helmut,Spannenberg, Anke,Fischer, Christine,Langer, Peter
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- Synthesis of (1H-1,2,3-Triazol-1-yl)acetic Acid Derivatives
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Abstract: A convenient synthetic approach to (1H-1,2,3-triazol-1-yl)acetic acid derivatives via the reaction of azidoacetamides with β-ketoesters and acetylacetone is proposed. Based on this strategy, 1,5-disubstituted 1,2,3-triazoles were prepared from available reagents under metal-free conditions. A one-pot protocol for the synthesis of (5-methyl-1H-1,2,3-triazol-1-yl)acetamides derived from N-substituted chloroacetamides is developed.
- Obushak, M. D.,Pokhodylo, N. T.,Savka, R. D.
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p. 1421 - 1431
(2020/10/02)
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- COMPOUNDS AS RAS INHIBITORS AND USE THEREOF
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A compound of Formula (Ia) or (Ib), or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
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Paragraph 0219
(2019/04/11)
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- NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3
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Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu3), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.
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Paragraph 0465-0466
(2015/12/30)
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- Phosphine-Mediated Iterative Arene Homologation Using Allenes
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A PPh3-mediated multicomponent reaction between o-phthalaldehydes, nucleophiles, and monosubstituted allenes furnishes functionalized non-C2-symmetric naphthalenes in synthetically useful yields. When the o-phthalaldehydes were reacted with 1,3-disubstituted allenes in the presence of PPh2Et, naphthalene derivatives were also obtained in up to quantitative yields. The mechanism of the latter transformation is straightforward: aldol addition followed by Wittig olefination and dehydration. The mechanism of the former is a tandem γ-umpolung/aldol/Wittig/dehydration process, as established by preparation of putative reaction intermediates and mass spectrometric analysis. This transformation can be applied iteratively to prepare anthracenes and tetracenes using carboxylic acids as pronucleophiles.
- Zhang, Kui,Cai, Lingchao,Jiang, Xing,Garcia-Garibay, Miguel A.,Kwon, Ohyun
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supporting information
p. 11258 - 11261
(2015/09/21)
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- PYRAZOLE DERIVATIVES, PREPARATION METHOD THEREOF, AND COMPOSITION FOR PREVENTION AND TREATMENT OF OSTEOPOROSIS CONTAINING SAME
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The present invention provides pyrazole derivative compounds and pharmaceutically acceptable salts thereof. The compounds of the present invention have an excellent effect of preventing and treating osteoporosis.
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Page/Page column 8
(2012/09/22)
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- Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ET(A) receptor selectivity
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Endothelins, ET-1, ET-2, and ET-3 are potent vasoconstricting and mitogenic 21-amino acid bicyclic peptides, which exert their effects upon binding to the ET(A) and ET(B) receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, and the ET(B) receptor mediates different effects in different tissues, including nitric oxide release from endothelial cells, and vasoconstriction in certain vascular cell types. Selective antagonists of endothelin receptor subtypes may prove useful in determining the role of endothelin in various tissue types and disease states, and hence as therapeutic agents for such diseases. The pyrrolidine carboxylic acid A-127722 has been disclosed as a potent and ET(A)-selective antagonist, and is currently undergoing clinical trials. In our efforts to find antagonists with altered selectivity (ET(A)-selective, ET(B)-selective, or nonselective), we investigated the SAR of the 2-substituent on the pyrrolidine. Compounds with alkyl groups at the 2-position possessed ET(A) selectivity improved over A-127722 (1400-fold selective), with the best of these compounds showing nearly 19,000-fold selectivity. Copyright (C) 1999 Elsevier Science Ltd.
- Boyd, Steven A.,Mantei, Robert A.,Tasker, Andrew S.,Liu, Gang,Sorensen, Bryan K.,Henry Jr., Kenneth J.,Von Geldern, Thomas W.,Winn, Martin,Wu-Wong, Jinshyun R.,Chiou, William J.,Dixon, Douglas B.,Hutchins, Charles W.,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.
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p. 991 - 1002
(2007/10/03)
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- Dihydro(alkylthio)(naphthylmethyl)oxopyrimidines: Novel non-nucleoside reverse transcriptase inhibitors of the S-DABO series
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Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6- (3-methylbenzyl)-4-oxopyrimidine (3c, MC 639) have been synthesized and tested as inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea with ethyl arylmethylacetoacetates furnished 5-alkyl-6- (arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford the required 2-alkylthio or 2- cycloalkylthio derivatives (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity was generally observed when 1-naphthylmethyl was replaced by the isomeric 2- naphthylmethyl moiety. The most active compounds showed activity in the low micromolar range with EC50 values comparable to that of nevirapine.
- Mai, Antonello,Artico, Marino,Sbardella, Gianluca,Quartarone, Silvana,Massa, Silvio,Loi, Anna G.,De Montis, Antonella,Scintu, Franca,Putzolu, Monica,La Colla, Paolo
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p. 1447 - 1454
(2007/10/03)
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- Substituted 2,6-substituted pyridine compounds having herbicidal activity
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Disclosed herein are substituted pyridine-3-monocarboxylate compounds in which a substituent is bonded to the pyridine ring at the 5-position through an oxygen atom.
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- Synthesis and Antiulcer Activity of 5,11-Dihydrobenzoxepinopyridines
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A series of substituted 5,11-dihydrobenzoxepinopyridines was synthesized and evaluated for antiulcer activity in water immersion/restrained stress ulcer assay in rats.Structure-activity relationships are described.Most of the tested compounds exhibited low affinity to the muscarinic acetylcholine receptor.The molecular features for the best activities are the 2-(diethylamino)ethylenediamine group at the 5-position of the oxepin ring and an oxepin skeleton rather than a thiepin or a pyran skeleton.Methyl and chlorine substitution on the benzene ring reduced the activity.Compound 11, 5-amino>-5,11-dihydrobenzoxepinopyridine trihydrochloride was selected for further evaluation.Synthesis and antiulcer activity of optically active 11 is described.There were no statistically significant differences between (+)-, (-), and (+/-)-11.Compound 11 showed weak antisecretory activity in pylorus-ligated rats.It is now under clinical evaluation as KW 5805.
- Kumazawa, Toshiaki,Harakawa, Hiroyuki,Obase, Hiroyuki,Oiji, Yoshimasa,Tanaka, Hiroshi,et al.
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p. 779 - 785
(2007/10/02)
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- Synthesis of some Isomeric 4,11-Dihydro-5H-benzoxocino or isoxazol-5-ones and Isomeric 4,5,10,11-Tetrahydrobenzocycloocta or isoxazol-5-ones
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The title compounds were prepared by acid-catalyzed cyclization of aryloxymethyl- or (2-arylethyl)-4-carboxymethylisoxazoles which in turn were synthesized from aryloxymethyl- or (2-arylethyl)isoxazole-4-carboxylic acids by Arndt-Eistert homologation.
- Deshayes, Christian,Chabannet, Michel,Gelin, Suzanne
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p. 1595 - 1598
(2007/10/02)
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