93002-98-3Relevant articles and documents
NOVEL LYSOPHOSPHATIDIC ACID DERIVATIVE
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Paragraph 1046-1048; 1133-1135, (2021/05/28)
PROBLEM TO BE SOLVED: To provide a compound that specifically activates an LPA4 receptor, and a pharmaceutical composition containing the same. SOLUTION: This invention relates to a novel lysophosphatidic acid derivative that has an agonistic action on an LPA4 receptor and is useful for the prevention and/or treatment of a disease with angiodysplasia caused by the LPA4 receptor, or a disease associated with angiopathy, or symptoms associated therewith. This invention also relates to a pharmaceutical composition containing the lysophosphatidic acid derivative. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
GPR35 MODULATORS
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Paragraph 00331, (2020/08/13)
Described herein are GPR35 modulators and methods of using these compounds in the treatment of diseases, disorders or conditions. Also described herein are pharmaceutical compositions containing such compounds.
Metal-free domino Cloke-Wilson rearrangement-hydration-dimerization of cyclopropane carbaldehydes: A facile access to oxybis(2-aryltetrahydrofuran) derivatives
Banerjee, Prabal,Dey, Raghunath,Rajput, Shruti
, (2020/03/13)
In this work, we have demonstrated a metal-free transformation of cyclopropane carbaldehydes to oxybis(2-aryltetrahydrofuran) derivatives via a domino Cloke-Wilson rearrangement-hydration-dimerization sequence. Commercially inexpensive p-toluene sulfonic acid (PTSA) was used as a Br?nsted acid catalyst, and reactions were conducted in an open-flask. Detection of reaction intermediates were carried to get an insight into the reaction pathway.
Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1
Zhou, Chao,Wu, Fangrui,Lu, Lianghao,Wei, Liping,Pai, Eric,Yao, Yuan,Song, Yongcheng
, (2017/02/15)
Post-translational modifications of histone play important roles in gene transcription. Aberrant methylation of histone lysine sidechains have been often found in cancer. Lysine specific demethylase 1 (LSD1), which can demethylate histone H3 lysine 4 (H3K4) and other proteins, has recently been found to be a drug target for acute myeloid leukemia. To understand structure activity/selectivity relationships of LSD1 inhibitors, several series of cyclopropylamine and related compounds were synthesized and tested for their activities against LSD1 and related monoamine oxidase (MAO) A and B. Several cyclopropylamine containing compounds were found to be highly potent and selective inhibitors of LSD1. A novel series cyclopropylimine compounds also exhibited strong inhibitory activity against LSD1.Structure activity relationships (SAR) of these compounds are discussed. Docking studies were performed to provide possible binding models of a representative compound in LSD1 and MAO-A. Moreover, these modeling studies can rationalize the observed SARs and selectivity.
TRIAZOLONE COMPOUNDS AND USES THEREOF
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Paragraph 00186, (2013/09/26)
The invention disclosed herein is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (I), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and/or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist.
Selective 5-hydroxytryptamine 2c receptor agonists derived from the lead compound tranylcypromine: Identification of drugs with antidepressant-like action
Sung, Jin Cho,Jensen, Niels H.,Kurome, Toru,Kadari, Sudhakar,Manzano, Michael L.,Malberg, Jessica E.,Caldarone, Barbara,Roth, Bryan L.,Kozikowski, Alan P.
experimental part, p. 1885 - 1902 (2009/12/07)
We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2- phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted be zene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT 2A and 5-HT2B, respectively (EC50) 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.
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.
Solvolysis of 1-[trans-2-(m- Orp-Substituted Phenyl)cyclopropyl]- 1-methylethyl p-Nitrobenzoates
Kusuyama, Yoshiaki
, p. 685 - 691 (2007/10/03)
The solvolyses of 1-[trans-2-(m- or p-substituted phenyl)cyclopropyl]-1-methylethyl p-nitrobenzoates in 80% aqueous acetone have been studied with regard to both reactivity and product composition. For the less reactive substituents such as m-Br, m-Cl, and m-CF3, the solvolysis products were the corresponding 2-(2-arylcyclopropyl)-2-propanol, indicating the cyclopropylmethyl cation intermediate. The ring-opened products increased as the electron-donating ability of the substituents increased. The application of the Yukawa-Tsuno equation to the reactivity afforded a ρ value of -1.43 and r value of 0.59 with a correlation coefficient of 0.997. A large value of r indicates the presence of the allylic cation intermediate where much more charge develops at the benzylic carbon for the derivatives with electron-donating substituents than is the case for the cyclopropylmethyl cation intermediate. Thus the solvolysis reaction proceeds via two independent pathways: one has a cyclopropyl cation intermediate and the other has a homoallylic cation intermediate.
ARYLCYCLOPROPANE PHOTOCHEMISTRY. UNUSUAL AROMATIC SUBSTITUENT EFFECTS ON THE PHOTOCHEMICAL REARRANGEMENT OF (2-ARYLCYCLOPROPYL)METHYL ACETATES TO 1-ARYLHOMOALLYL ACETATES.
Hixson,Franke,Gere,Xing
, p. 3601 - 3610 (2007/10/02)
Irradiation of trans(2-arylcyclopropyl)methyl acetates a 4-butenyl-1-arylacetate (7a,b,d-h) via an ionic mechanism from the singlet state. Similar rearrangements occurred with exo-(1,1a,6,6a-tetrahydrocycloprop left bracket a right bracket inden-1-yl)methyl acetate and the 4-cyano derivative. Excited state reaction rate constants were determined from reactant fluorescence lifetimes and product quantum yields. It is concluded that the rate-determining step involves conversion of the initially formed aromatic excited state to a reactive cyclopropane excited state and that cyclopropane to aromatic ring charge transfer enhances this process.
