- Inhibition of hedgehog signaling by stereochemically defined des-triazole itraconazole analogues
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Dysregulation of the hedgehog (Hh) signaling pathway is associated with cancer occurrence and development in various malignancies. Previous structure-activity relationships (SAR) studies have provided potent Itraconazole (ITZ) analogues as Hh pathway antagonists. To further expand on our SAR for the ITZ scaffold, we synthesized and evaluated a series of compounds focused on replacing the triazole. Our results demonstrate that the triazole region is amenable to modification to a variety of different moieties; with a single methyl group representing the most favorable substituent. In addition, nonpolar substituents were more active than polar substituents. These SAR results provide valuable insight into the continued exploration of ITZ analogues as Hh pathway antagonists.
- Wen, Jiachen,Teske, Kelly A.,Kyle Hadden
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supporting information
(2020/01/02)
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- POLYCYCLIC PYRAZOLINONE DERIVATIVE AND HERBICIDE COMPRISING SAME AS EFFECTIVE COMPONENT THEREOF
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Provided are a polycyclic pyrazolinone derivative indicated by general formula (1) (in the formula, R1, X1, X2, X3, and Y indicate the definitions provided in the Specification) and a herbicide comprising same as effective component thereof.
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Paragraph 0449; 0450
(2016/02/19)
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- Diol compounds as intermediates for preparing antimycotic compounds
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A compound of formula (II), wherein R1is chloro, fluoro or trifluoromethyl; R2is hydrogen, chloro, fluoro or trifluoromethyl; and R is hydrogen or a protective group for the hydroxy moiety useful as an intermediate for the synthesis
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- Studies on agents with vasodilator and β-blocking activities. V. Synthesis and pharmacological activity of the optical isomers of TZC-5665
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Synthesis of the four optical isomers of TZC-5665 (1), a candidate for the treatment of congestive heart failure, was achieved by the reaction of chiral diaminopyridazinone (2) with chiral glycidyl ether (3). The hypotensive and β-blocking activities of 1 and its optical isomers were examined when given intravenously into anesthetized rats. Furthermore these compounds were evaluated for inhibitory activity on cAMP phosphodiesterase III. Among the four optical isomers, R(A),S(B)-one (1c) possessed the essential activities of TZC-5665 (1).
- Seki, Toshimi,Kanada, Arihiro,Nakao, Tomio,Shiraiwa, Masahumi,Asano, Hajime,Miyazawa, Katuhiko,Ishimori, Tsutomu,Minami, Nobuyoshi,Shibata, Kenyu,Yasuda, Kikuo
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- Asymmetric hydrogenation of α-keto acid derivatives by rhodium-{amidophosphine-phosphinite} catalysts
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The enantioselective hydrogenation of several α-keto esters (3a-f, 5a-j), α-keto amides (7a-e) and isatine derivatives (9a-d) with a set of four representative neutral homogeneous rhodium-amidophosphine-phosphinite catalysts has been investigated. Trifluoroacetate-Rh-AMPP catalytic precursors promoted the rapid, efficient synthesis of aliphatic α-hydroxy esters 4a-f in moderate to high enantioselectivities (66-95% eel, in contrast to most aromatic α-hydroxy esters 6a-j (8-81% eel. Best enantioselectivities for α-hydroxy amides 8a-e (85-95% eel and dioxindoIes 10a-d (80-94% eel were obtained with chloro-Rh-AMPP precursors. It is proposed that, contrary to α-keto amides, α-keto esters do not chelate onto the rhodium center and that, in such circumstances, the asymmetric induction is mainly controlled by the steric hindrance around the C=O function.
- Carpentier, Jean-Francois,Mortreux, Andre
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p. 1083 - 1099
(2007/10/03)
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