82475-75-0Relevant academic research and scientific papers
4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides
Meyers, Marvin J.,Liu, Jianguang,Xu, Jing,Leng, Fang,Guan, Jiantong,Liu, Zhijun,McNitt, Sarah A.,Qin, Limei,Dai, Linglin,Ma, Hongwei,Adah, Dickson,Zhao, Siting,Li, Xiaofen,Polino, Alex J.,Nasamu, Armiyaw S.,Goldberg, Daniel E.,Liu, Xiaorong,Lu, Yongzhi,Tu, Zhengchao,Chen, Xiaoping,Tortorella, Micky D.
supporting information, p. 3503 - 3512 (2019/03/29)
Identification of novel chemotypes with antimalarial efficacy is imperative to combat the rise of Plasmodium species resistant to current antimalarial drugs. We have used a hybrid target-phenotype approach to identify and evaluate novel chemotypes for malaria. In our search for drug-like aspartic protease inhibitors in publicly available phenotypic antimalarial databases, we identified GNF-Pf-4691, a 4-aryl-N-benzylpyrrolidine-3-carboxamide, as having a structure reminiscent of known inhibitors of aspartic proteases. Extensive profiling of the two terminal aryl rings revealed a structure-activity relationship in which relatively few substituents are tolerated at the benzylic position, but the 3-aryl position tolerates a range of hydrophobic groups and some heterocycles. Out of this effort, we identified (+)-54b (CWHM-1008) as a lead compound. 54b has EC50 values of 46 and 21 nM against drug-sensitive Plasmodium falciparum 3D7 and drug-resistant Dd2 strains, respectively. Furthermore, 54b has a long half-life in mice (4.4 h) and is orally efficacious in a mouse model of malaria (qd; ED99 ～ 30 mg/kg/day). Thus, the 4-aryl-N-benzylpyrrolidine-3-carboxamide chemotype is a promising novel chemotype for malaria drug discovery.
(2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands
Kamińska, Katarzyna,Ziemba, Julia,Ner, Joanna,Schwed, Johannes Stephan,?azewska, Dorota,Wi?cek, Ma?gorzata,Karcz, Tadeusz,Olejarz, Agnieszka,Latacz, Gniewomir,Kuder, Kamil,Kottke, Tim,Zygmunt, Ma?gorzata,Sapa, Jacek,Karolak-Wojciechowska, Janina,Stark, Holger,Kie?-Kononowicz, Katarzyna
, p. 238 - 251 (2015/09/22)
Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives. A series of novel compounds in the group of 4-methylpiperazine-1,3,5-triazine-2-amines were designed and obtained. Considered structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties. Their affinities to histamine H4 receptors were evaluated in radioligand binding assays with use of Sf9 cells, transiently expressing human H4R. Pharmacological studies results allowed to identify 4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (Ki Combining double low line 253 nM) as the most potent compound in the present series.
PYRROLIDINE CARBOXAMIDE COMPOUNDS
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Page/Page column 48-49, (2010/07/10)
Pyrrolidine carboxamide compounds are provided. Some such pyrrolidine carboxamide compounds include agonists of sst4 which may be useful for the treatment and prevention of pain and inflammatory disorders.
Nitrogen-containing heterocyclic compound and use thereof
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Page/Page column 42; 43, (2009/07/03)
The present invention relates to a compound represented by the formula wherein ring A is a nitrogen-containing heterocycle optionally further having substituent(s), ring B is an aromatic ring optionally having substituent(s), ring C is a cyclic group optionally having substituent(s), R1 is a hydrogen atom, a hydrocarbon group optionally having substituent(s), an acyl group, a heterocyclic group optionally having substituent(s) or an amino group optionally having substituent(s), R2 is an optionally halogenated C1-6 alkyl group, m and n are each an integer of 0 to 5, m+n is an integer of 2 to 5, and is a single bond or a double bond, or a salt thereof and the like. Since the compound has a superior tachykinin receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of various diseases such as lower urinary tract diseases, gastrointestinal diseases, central nervous system diseases and the like.
PHARMACEUTICALLY ACTIVE BENZOXAZOLE, BENZTHIAZOLE AND BENZIMIDAZOLE ACID DERIVATIVES
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Page 36, (2010/02/07)
Compounds of formula (I): wherein R1, R2 and R3 are independently, hydrogen, halogen, CF3, OR6, NR7R8, NR8COR10, NR8SO2R10 or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy or NR7R8; R4 is NR8CONR8R9, NR8COR9, NR8SO2R9, or W-CONR8R9, where W is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; and R5 is Formula (A) methods for their synthesis, pharmaceutical compositions comprising them and their use in medicine, in particular for the treatment of cancer.
SUBSTITUTED ARYLALKYLAMINES AS NEUROKININ ANTAGONISTS
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, (2008/06/13)
Aralkylamine derivatives of formula (I) and their salts are new: A1 = CH2R6, OR6, NR6R7, SOeR13, (CR6R7)qOR6, (CR6R7)qNR6R7 or (CR6R7)qSOeR13; q = 1-6; A2 = H; or A1+A2 = O, CR6R7, NOR6 or S; Q = R5-phenyl, R5-naphthyl, SR6, NR6R7, OR6 or R5-heteroaryl; T
The design and synthesis of novel NK1/NK2 dual antagonists
Reichard, Gregory A.,Ball, Zachary T.,Aslanian, Robert,Anthes, John C.,Shih, Neng-Yang,Piwinski, John J.
, p. 2329 - 2332 (2007/10/03)
Functional probing of the backbone of the Sanofi NK2 antagonist SR 48968 has resulted in the discovery of two new classes of NK1/NK2 dual antagonists: the diamine class and the oxime class. The addition of the amino or the oxime functional group results in the reversal of the stereochemical preference of the NK2 receptor. (C) 2000 Elsevier Science Ltd.
Certain 2,4-pentadienamide pestacides
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, (2008/06/13)
The present application discloses pesticidally active compounds of formula I: or a salt thereof, wherein Q is an monocyclic aromatic ring, or Q is a dihalovinyl group or a group R7 --C=C-- where R7 is C1-4 alkyl, tri Csub
