858488-66-1Relevant articles and documents
Potent Antimalarial 2-Pyrazolyl Quinolone bc1 (Qi) Inhibitors with Improved Drug-like Properties
David Hong,Leung, Suet C.,Amporndanai, Kangsa,Davies, Jill,Priestley, Richard S.,Nixon, Gemma L.,Berry, Neil G.,Samar Hasnain,Antonyuk, Svetlana,Ward, Stephen A.,Biagini, Giancarlo A.,O'Neill, Paul M.
, p. 1205 - 1210 (2018/11/23)
A series of 2-pyrazolyl quinolones has been designed and synthesized in 5-7 steps to optimize for both in vitro antimalarial potency and various in vitro drug metabolism and pharmacokinetics (DMPK) features. The most potent compounds display no cross-resistance with multidrug resistant parasite strains (W2) compared to drug sensitive strains (3D7), with IC50 (concentration of drug required to achieve half maximal growth suppression) values in the range of 15-33 nM. Furthermore, members of the series retain moderate activity against the atovaquone-resistant parasite isolate (TM90C2B). The described 2-pyrazoyl series displays improved DMPK properties, including improved aqueous solubility compared to previously reported quinolone series and acceptable safety margin through in vitro cytotoxicity assessment. The 2-pyrazolyl quinolones are believed to bind to the ubiquinone-reducing Qi site of the parasite bc1 complex, which is supported by crystallographic studies of bovine cytochrome bc1 complex.
Design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents
Vyas, Vivek K.,Variya, Bhavesh,Ghate, Manjunath D.
, p. 385 - 393 (2014/07/07)
In continuation of our research for novel human dihydroorotate dehydrogenase (hDHODH) inhibitors, herein we reported design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives. Human DHODH enzyme inhibition a
Design and synthesis of 4-quinolinone 2-carboxamides as calpain inhibitors
Nam, Dong Hyuk,Lee, Kwang Seob,Kim, Sang Hoon,Kim, Sung Min,Jung, Seo Yun,Chung, Sung Hyun,Kim, Hyoung Ja,Kim, Nam Doo,Jin, Changbae,Lee, Yong Sup
, p. 205 - 209 (2008/09/17)
Calpains are involved in a variety of calcium-regulated cellular processes, such as signal transduction, cell proliferation, differentiation, and apoptosis. Excessive calpain activation contributes to serious cellular damage and has been reported in many pathological conditions. 4-Quinolinone 2-carboxamide derivatives were prepared and evaluated for μ-calpain inhibitory activities. Of the compounds synthesized, 3a and 3k, which possess a primary amide and 4-methoxyphenethyl amide at P1′ region, were found to most potently inhibit μ-calpain with IC50 values of 0.71 ± 0.07 and 0.73 ± 0.23 μM, respectively. On the other hand, the incorporation of pyridine-containing amides decreased inhibitory activity.
Structure-activity relationship of quinoline derivatives as potent and selective α2c-adrenoceptor antagonists
H?glund, Iisa P. J.,Silver, Satu,Engstr?m, Mia T.,Salo, Harri,Tauber, Andrei,Kyyr?nen, Hanna-Kaisa,Saarenketo, Pauli,Hoffrén, Anna-Marja,Kokko, Kurt,Pohjanoksa, Katariina,Sallinen, Jukka,Savola, Juha-Matti,Wurster, Siegfried,Kallatsa, Oili A.
, p. 6351 - 6363 (2007/10/03)
Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human α2- adrenoceptor subtypes (α2A, α2B, and α2C). A number of compounds with good antagonist potencies against the α2C-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl)phenylamino]quinolin-3-yl}methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the α2c-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the α2C- adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.
2-AMINOCARBONYL-QUINOLINE COMPOUNDS AS PLATELET ADENOSINE DIPHOSPHATE RECEPTOR ANTAGONISTS
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Page 45, (2010/02/07)
Compounds of formula (I), where m, n, R1, R2, R3, R4 and R6 are described herein, are useful as inhibitors of platelet adenosine diphosphate. Pharmaceutical compositions containing these compounds, methods of using these compounds as antithrombotic agents and processes for synthesizing these compounds are also described herein.
Novel ester or amide derivatives
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Page 7, (2008/06/13)
An ester or amide derivative represented by the general formula (I) or a pharmaceutically acceptable salt thereof. Particularly, an ester or amide derivative of 4-oxo-1,4-dihydroqunoline-2-carboxylic acid represented by the general formula (I′) or (I″), o
Platelet adenosine diphosphate receptor antagonists
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, (2008/06/13)
Compounds of the following formula (I): where a, b, R1, R2, R4 and R6 are described herein, are useful as inhibitors of platelet adenosine diphosphate. Pharmaceutical compositions containing these compounds, met
NOVEL ESTER OR AMIDE DERIVATIVES
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, (2008/06/13)
An ester or amide derivative represented by the general formula (I) or a pharmaceutically acceptable salt thereof. Particularly, an ester or amide derivative of 4-oxo-1,4-dihydroqunoline-2-carboxylic acid represented by the general formula (I') or (I''), or a pharmaceutically acceptable salt thereof.
