31982-85-1Relevant articles and documents
Synthesis method of trans 1 and 2 - cyclohexane dicarboxylic acid monomethylester
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Paragraph 0033-0039; 0040-0043, (2021/08/25)
The invention provides a synthesis method of trans 1 and 2 - cyclohexane dicarboxylic acid monomethylester, and belongs to the field of organic synthesis. The trans 1-2 -cyclohexane dicarboxylic acid monomethylester synthesis method comprises the following steps: trans-cyclohexane -1 and 2 -dicarboxylic acid anhydride. The methanol and solvent is added to the reaction vessel, stirred and purified to obtain the target product trans 1, 2 - cyclohexanedicarboxylate, wherein the solvent is any one or more of tetrahydrofuran, 2 - methyltetrahydrofuran, benzene, toluene, methylene chloride, chloroform, ethyl acetate, methyl acetate or diethyl ether. Since a specific solvent is selected for the reaction solvent, racemization does not occur in the process of synthesizing trans 1 and 2 - cyclohexane dicarboxylic acid monomethyl ester, and the trans ee and 1 cyclohexane dicarboxylic acid monomethyl ester with higher 2 - value can be finally obtained.
Exploring the active conformation of cyclohexane carboxylate positive allosteric modulators of the type 4 metabotropic glutamate receptor
Rovira, Xavier,Harrak, Youssef,Trapero, Ana,Gonzlez-Bulnes, Patricia,Malhaire, Fanny,Pin, Jean-Philippe,Goudet, Cyril,Giraldo, Jesffls,Llebaria, Amadeu
, p. 2685 - 2698 (2015/02/02)
The active conformation of a family of metabotropic glutamate receptor subtype 4 (mGlu4) positive allosteric modulators (PAMs) with the cyclohexane 1,2-dicarboxylic scaffold present in cis-2-(3,5-dichlorophenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041) was investigated by testing structurally similar six-membered ring compounds that have a locked conformation. The norbornane and cyclohexane molecules designed as mGlu4 conformational probes and the enantiomers of the trans diastereomer were computationally characterized and tested in mGlu4 pharmacological assays. The results support a VU0155041 active conformation, with the chair cyclohexane having the aromatic amide substituent in an axial position and the carboxylate in an equatorial position. Moreover, the receptor displays enantiomeric discrimination of the chiral PAMs. The constructed pharmacophore characterized a highly constrained mGlu4 allosteric binding site, thus providing a step forward in structure-based drug design for mGlu4 PAMs.
(1 R,2 R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3- b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A potent and highly selective cathepsin k inhibitor for the treatment of osteoarthritis
Dossetter, Alexander G.,Beeley, Howard,Bowyer, Jonathan,Cook, Calum R.,Crawford, James J.,Finlayson, Jonathan E.,Heron, Nicola M.,Heyes, Christine,Highton, Adrian J.,Hudson, Julian A.,Jestel, Anja,Kenny, Peter W.,Krapp, Stephan,Martin, Scott,MacFaul, Philip A.,McGuire, Thomas M.,Gutierrez, Pablo Morentin,Morley, Andrew D.,Morris, Jeffrey J.,Page, Ken M.,Ribeiro, Lyn Rosenbrier,Sawney, Helen,Steinbacher, Stefan,Smith, Caroline,Vickers, Madeleine
scheme or table, p. 6363 - 6374 (2012/09/25)
Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.
