31420-66-3Relevant articles and documents
USE OF T-TYPE CALCIUM CHANNEL BLOCKER FOR TREATING PRURITUS
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Paragraph 0186-0188; 0228-0230, (2022/02/19)
A medicament for treating or preventing pruritus is provided. For the medicament for treating or preventing pruritus, a compound having a blocking action on Cav3.2T-type calcium channels represented by General Formulas (I) to (VI), a tautomer of the compo
BICYCLIC KETONE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 194; 195, (2019/02/02)
The invention provides novel compounds having the general formula (I): (I) wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.
Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation of O-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR
Annunziato, Giannamaria,Pieroni, Marco,Benoni, Roberto,Campanini, Barbara,Pertinhez, Thelma A.,Pecchini, Chiara,Bruno, Agostino,Magalh?es, Joana,Bettati, Stefano,Franko, Nina,Mozzarelli, Andrea,Costantino, Gabriele
, p. 78 - 87 (2016/12/23)
Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been dee
Cyclopropane derivatives as potential human serine racemase inhibitors: Unveiling novel insights into a difficult target
Beato, Claudia,Pecchini, Chiara,Cocconcelli, Chiara,Campanini, Barbara,Marchetti, Marialaura,Pieroni, Marco,Mozzarelli, Andrea,Costantino, Gabriele
, p. 645 - 652 (2016/05/09)
d-Serine is the co-agonist of NMDA receptors and binds to the so-called glycine site. d-Serine is synthesized by human serine racemase (SR). Over activation of NMDA receptors is involved in many neurodegenerative diseases and, therefore, the inhibition of SR might represent a novel strategy for the treatment of these pathologies. SR is a very difficult target, with only few compounds so far identified exhibiting weak inhibitory activity. This study was aimed at the identification of novel SR inhibitor by mimicking malonic acid, the best-known SR inhibitor, with a cyclopropane scaffold. We developed, synthesized, and tested a series of cyclopropane dicarboxylic acid derivatives, complementing the synthetic effort with molecular docking. We identified few compounds that bind SR in high micromolar range with a lack of significant correlation between experimental and predicted binding affinities. The thorough analysis of the results can be exploited for the development of more potent SR inhibitors.
Conformationally restrained carbamoylcholine homologues. Synthesis, pharmacology at neuronal nicotinic acetylcholine receptors and biostructural considerations
De La Fuente Revenga, Mario,Balle, Thomas,Jensen, Anders A.,Fr?lund, Bente
, p. 352 - 362 (2015/09/01)
Exploration of small selective ligands for the nicotinic acetylcholine receptors (nAChRs) based on acetylcholine (ACh) has led to the development of potent agonists with clear preference for the α4β2 nAChR, the most prevalent nAChR subtype in the central nervous system. In this work we present the continuation of these efforts aimed at increasing this subtype selectivity by introduction of conformational restriction in the carbamoylcholine homologue, 3-(dimethylaminobutyl) dimethylcarbamate (DMABC). Our results highlight the importance of the N-carbamoyl substitution in α4β2-subtype selectivity. Moreover, we have confirmed the non-linear conformation of DMABC bound to nAChRs suggested by recent crystal structures of the compound in complex with the Lymnaea stagnalis ACh binding protein.
Enantioselective bacterial hydrolysis of amido esters and diamides derived from (±)-trans-cyclopropane-1,2-dicarboxylic acid
Hugentobler, Katharina G.,Rebolledo, Francisca
, p. 615 - 623 (2014/01/06)
Different optically active amido esters, mixed acid esters, amido acids, and diamides derived from trans-cyclopropane-1,2-dicarboxylic acid were prepared from the commercially available diethyl (±)-trans-cyclopropane-1,2- dicarboxylate. The key step was the Rhodococcus rhodochrous IFO 15564 catalyzed hydrolysis of the corresponding racemic amide. The amidase present in this microorganism showed moderate to high enantioselectivity towards these substrates. In addition a simple and efficient Curtius rearrangement of some of the enzymatically prepared cyclopropanecarboxylic acids allowed us to obtain optically active β-aminocyclopropanecarboxylic acid derivatives with high yields and enantiomeric excesses. The Royal Society of Chemistry.
NOVEL HEPATITIS C VIRUS INHIBITORS
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Page/Page column 129, (2013/07/05)
The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
2-substituted-(2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1- yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 1. Effects of alkyl, arylalkyl, and diarylalkyl substitution
Ornstein, Paul L.,Bleisch, Thomas J.,Arnold, M. Brian,Wright, Rebecca A.,Johnson, Bryan G.,Schoepp, Darryle D.
, p. 346 - 357 (2007/10/03)
In this paper, we describe the synthesis of a series of α-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into an antagonist. All of the compounds were prepared and tested as a aeries of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [3H]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial. The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.010 μM in the [3H]Glu binding assay, was 52-fold more potent than 2, whose IC50 was 0.47 μM.
Synthesis of Cyclopropyl Carbocyclic Nucleosides
Csuk, Rene,Scholz, Yvonne von
, p. 10431 - 10442 (2007/10/02)
As representatives of a novel class of carboxylic nucleoside analogues (+/-)-cis-, (-)-cis and (+/-)-trans 9-(2-hydroxymethylcyclopropyl)-adenine (= -methanol) were synthesized from the corresponding dialkyl 1,2-cyclopropane dicarboxylates.
