脯氨酸消旋酶 (PRAC) 催化l-脯氨酸和d-脯氨酸相互转化,是真核病原体如克氏锥虫、间日锥虫和艰难梭菌的重要因子。如果发现T的不可逆抑制剂。 cruzi PRAC (TcPRAC)导致了南美锥虫病的创新疗法,迄今为止尚未发现Cd PRAC 抑制剂。然而,由于近年来发病率增加,艰难梭菌被认为是威胁健康的主要原因。在这项工作中,我们考虑了Tc PRAC 和Cd之间的相似性PRAC 酶设计新的Cd PRAC 抑制剂。从( E ) 4-oxopent-2-enoic acid Tc PRAC 不可逆抑制剂开始,我们合成了4-芳基取代的类似物,并评估了它们对艰难梭菌11 株的Cd PRAC 酶抑制作用。该研究产生了有希望的候选物,并允许鉴定 ( E )-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20,该物质被选择用于补充体内研究但未在体内揭示毒性。
Studies on antirheumatic agents. 3-Benzoylpropionic acid derivatives.
作者:KAZUYA KAMEO、KUNIO OGAWA、KIMIYO TAKESHITA、SHIRO NAKAIKE、KAZUYUKI TOMISAWA、KAORU SOTA
DOI:10.1248/cpb.36.2050
日期:——
As part of the search for new antirheumatic agents, three types of 3-benzoylpropionic acid derivatives having a mercapto moiety in their structures were prepared, and tested for suppressing activity on adjuvant arthritis in Sprague-Dawley rats. A structure-activity relationship study showed that substitution on the phenyl ring contributed to the activity and the most favorable substituent was different in each type of derivative.
申请人:The United States of America as represented by the Secretary of the Army
公开号:US03940404A1
公开(公告)日:1976-02-24
A series of 2-aryl-6-trifluoromethyl-4-pyridylcarbinolamines is herein disclosed which has value in treatment of plasmodial infections. The compounds have substituted phenyl groups at position 2- on the pyridine moiety, with the electronegative substituents present on the phenyl nuclei. The syntheses of such series is described, together with a method for separation of racemates of a representative 4-pyridylcarbinolamine type.
Efficient Synthesis of Uracil-Derived Hexa- and Tetrahydropyrido[2,3-<i>d</i>]pyrimidines
作者:Nikita Tolstoluzhsky、Pavlo Nikolaienko、Nikolay Gorobets、Erik V. Van der Eycken、Nadezhda Kolos
DOI:10.1002/ejoc.201300683
日期:2013.8
esters leads to hexahydropyrido[2,3-d]pyrimidine-5-carboxylic acids or the corresponding methyl esters in high to excellent yields. One-pot oxidation of the acid derivatives with CAN is accompanied by decarboxylation to give tetrahydropyrido[2,3-d]pyrimidines, while oxidation with bromine resulted in the formation of tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acids. The aromatization of methyl hexahydropyrido[2
6-氨基-1,3-二甲基尿嘧啶与 3-(杂)芳酰基丙烯酸及其甲酯的反应生成六氢吡啶并[2,3-d]嘧啶-5-羧酸或相应的甲酯,收率高至极好. 酸衍生物用 CAN 的一锅氧化伴随着脱羧作用得到四氢吡啶并[2,3-d]嘧啶,而用溴氧化导致形成四氢吡啶并[2,3-d]嘧啶-5-羧酸。在环境条件下通过 K2CO3 介导的空气氧化实现了甲基六氢吡啶并 [2,3-d]pyrimidine-5-carboxylates 的芳构化。
Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents
A series of novel (E)-4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against
The highly diastereoselective synthesis of perfluoroalkyl-containing pyrano[3,4-c]pyrroles has been accomplished via a cascade process involving Michael addition, Passerini-type reaction, Mumm rearrangement and an oxo-Diels–Alder reaction. This domino transformation of isocyanides, methyl perfluoroalk-2-ynoates and 3-aroyl (or heteroyl) acrylic acids proceeded smoothly at room temperature and led to
含全氟烷基的吡喃并[3,4- c ]吡咯的高度非对映选择性合成是通过级联过程完成的,该过程涉及迈克尔加成,Passerini型反应,Mumm重排和羰基-狄尔斯-阿尔德反应。异氰酸酯,全氟烷-2-甲基丙烯酸甲酯和3-芳酰基(或杂芳基)丙烯酸的多米诺骨转化在室温下平稳进行,并导致形成具有高官能团相容性的高非对映选择性目标化合物,并具有良好的产率。