142793-24-6Relevant articles and documents
CARBOXYLIC ACID AROMATIC 1,2-CYCLOPROPYLAMIDES
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Paragraph 0893-0902, (2019/06/20)
The present invention relates to carboxylic acid aromatic 1,2-cyclopropylamides of general formula (I) as described and defined herein, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neurogenic disorder, as a sole agent or in combination with other active ingredients.
Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis
Chandgude, Ajay L.,Fasan, Rudi
, p. 15852 - 15856 (2018/11/23)
A chemobiocatalytic strategy for the highly stereoselective synthesis of nitrile-substituted cyclopropanes is reported. The present approach relies on an asymmetric olefin cyclopropanation reaction catalyzed by an engineered myoglobin in the presence of ex situ generated diazoacetonitrile within a compartmentalized reaction system. This method enabled the efficient transformation of a broad range of olefin substrates at a preparative scale with up to 99.9 % de and ee and up to 5600 turnovers. The enzymatic product could be further elaborated to afford a variety of functionalized chiral cyclopropanes. This work expands the range of synthetically valuable, abiotic transformations accessible through biocatalysis and paves the way to the practical and safe exploitation of diazoacetonitrile in biocatalytic carbene transfer reactions.
Synthesis and in vitro evaluation of novel N-cycloalkylcarbamates as potential cholinesterase inhibitors
Horáková, Eva,Drabina, Pavel,Br??ková, Lenka,?těpánková, ?árka,Vor?áková, Katarína,Sedlák, Milo?
, p. 2143 - 2153 (2017/09/25)
Abstract: This present paper describes the preparation and characterization of a series of O-substituted N-cycloalkylcarbamate derivatives. These compounds were tested as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All studied carbamates exhibited moderate inhibitory activity of both cholinesterases with values of IC50 in the range of 36.1–78.6?μM for AChE and 9.8–215.4?μM for BChE, respectively. These values are comparable with those values of inhibition obtained with the established drug rivastigmine. The cytotoxicity of all carbamates was evaluated using standard in vitro test with Jurkat cells. Many of the studied carbamates can be considered as promising compounds for potential medicinal applications with regard to their inhibitory activity as well as negligible cytotoxicity.
The synergistic effect of copper chromite spinel nanoparticles (CuCr2O4) and basic ionic liquid on the synthesis of cyclopropanecarboxylic acids
Ghasemi, Mohammad Hadi,Kowsari, Elaheh
, p. 7963 - 7975 (2016/11/25)
Abstract: An efficient synthesis of cyclopropanecarboxylic acids using copper chromite spinel nanoparticles and basic ionic liquid is described. In this study, a relatively simple method starting with trans-cinnamic acid for the synthesis of (±)-trans-2-phenylcyclopropanecarboxylic acid, a key intermediate in the synthesis of tranylcypromine sulfate as an active pharmaceutical ingredient, was employed. Using a combination of basic ionic liquid [Bmim]OH and copper chromite spinel nanoparticles as a catalytic system, the best results were obtained in THF as a polar solvent. This method is a useful alternative to other approaches described in the literature. The use of commercially available chemicals, decreased environmental hazards, with no need for the separation of stereoisomers, and consequently a reduced number of overall steps, are the advantages of this approach that make it an appropriate choice at an increased scale. Graphical Abstract: [Figure not available: see fulltext.]
Tranylcypromine substituted cis -hydroxycyclobutylnaphthamides as potent and selective dopamine D3 receptor antagonists
Chen, Jianyong,Levant, Beth,Jiang, Cheng,Keck, Thomas M.,Newman, Amy Hauck,Wang, Shaomeng
, p. 4962 - 4968 (2014/07/07)
We report a class of potent and selective dopamine D3 receptor antagonists based upon tranylcypromine. Although tranylcypromine has a low affinity for the rat D3 receptor (Ki = 12.8 μM), our efforts have yielded (1R,2S)-11 (CJ-1882), which has Ki values of 2.7 and 2.8 nM at the rat and human dopamine D3 receptors, respectively, and displays respective selectivities of >10000-fold and 223-fold over the rat and human D2 receptors. Evaluation in a β-arrestin functional assay showed that (1R,2S)-11 is a potent and competitive antagonist at the human D3 receptor.
Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: Facile access to spiro 3,3′-cyclopropyl oxindoles
Ladd, Carolyn L.,Sustac Roman, Daniela,Charette, André B.
supporting information, p. 1350 - 1353 (2013/05/09)
The Pd-catalyzed, Ag(I)-mediated intramolecular direct arylation of cyclopropane C-H bonds is described. Various spiro 3,3′-cyclopropyl oxindoles can be obtained in good to excellent yields from easily accessible 2-bromoanilides. The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.
Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors
Tsai, Ting-Yueh,Hsu, Tsu,Chen, Chiung-Tong,Cheng, Jai-Hong,Yeh, Teng-Kuang,Chen, Xin,Huang, Chung-Yu,Chang, Chung-Nien,Yeh, Kai-Chia,Hsieh, Su-Huei,Chien, Chia-Hui,Chang, Yi-Wei,Huang, Chih-Hsiang,Huang, Yu-Wen,Huang, Chen-Lung,Wu, Ssu-Hui,Wang, Min-Hsien,Lu, Cheng-Tai,Chao, Yu-Sheng,Jiaang, Weir-Torn
experimental part, p. 2388 - 2399 (2009/09/05)
A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC50 values of 100 nM with excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. The studies identified a potent and selective DPP-IV inhibitor 24b, which exhibited the ability to both significantly inhibit plasma DPP-IV activity in rats and improve glucose tolerance in lean mice and diet induced obese mice.
Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder
Pryde, David C.,Cook, Andrew S.,Burring, Denise J.,Jones, Lyn H.,Foll, Stephanie,Platts, Michelle Y.,Sanderson, Vivienne,Corless, Martin,Stobie, Alan,Middleton, Donald S.,Foster, Laura,Barker, Laura,Van Der Graaf, Piet,Stacey, Peter,Kohl, Christopher,Coggon, Sara,Beaumont, Kevin
, p. 142 - 159 (2007/10/03)
A series of substituted glutaramides were synthesised using Candoxatrilat 1 as a lead and evaluated for potency against neutral endopeptidase (NEP) as a potential treatment for female sexual arousal disorder (FSAD). In this paper, we describe studies in which we were able to increase NEP activity substantially over the levels reported for previous compounds from this programme by appropriate substitution in both the P1′ and P2′ regions. Optimisation led to the 4-chlorophenpropylamide S-30 which was selected as a candidate for further study.
Synthesis and structure-activity relationship of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitriles as EGFR tyrosine kinase inhibitors
Pannala, Madhavi,Kher, Sunil,Wilson, Norma,Gaudette, John,Sircar, Ila,Zhang, Shao-Hui,Bakhirev, Alexei,Yang, Guang,Yuen, Phoebe,Gorcsan, Frank,Sakurai, Naoki,Barbosa, Miguel,Cheng, Jie-Fei
, p. 5978 - 5982 (2008/03/11)
Synthesis and structure-activity relationship of a series of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitrile derivatives as EGFR inhibitors is described. Compounds 29 and 30 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the functional cellular assay. They are moderately selective against other types of tyrosine kinases.
The first cyclopropanation reaction of unmasked α,β-unsaturated carboxylic acids: Direct and complete stereospecific synthesis of cyclopropanecarboxylic acids promoted by Sm/CHl3
Concellon, Jose M.,Rodriguez-Solla, Humberto,Simal, Carmen
, p. 2685 - 2688 (2008/02/08)
Equation Presented A samarium-promoted cyclopropanation of unmasked α,β-unsaturated acids is described. This reaction can be carried out on (E)- or (Z)α,β-unsaturated carboxylic acids. In all cases the process is completely stereospecific and stereoselective. A mechanism has been proposed to explain the cyclopropanation reaction.
