26893-22-1Relevant academic research and scientific papers
Identification of potent and selective inhibitors of PDGF receptor autophosphorylation
Furuta, Takayuki,Sakai, Teruyuki,Senga, Terufumi,Osawa, Tatsushi,Kubo, Kazuo,Shimizu, Toshiyuki,Suzuki, Rika,Yoshino, Tetsuya,Endo, Megumi,Miwa, Atsushi
, p. 2186 - 2192 (2007/10/03)
We report the structure-activity relationship of quinoline and quinazoline derivatives, which include urea, thiourea, urethane, and acylthiourea groups, as inhibitors of the platelet-derived growth factor (PDGF) receptor autophosphorylation. Our previous studies showed that the quinoline and quinazoline derivatives including urea, thiourea, and carbamate groups were highly potent compounds as the PDGF receptor autophosphorylation inhibitor, but these compounds did not exhibit receptor selectivity between the PDGF receptor and the c-kit receptor. As a result of further synthesis and biological evaluation, we have found that the quinoline and quinazoline-acylthiourea derivatives showed not only good inhibitory activity for the PDGF receptor but also receptor selectivity between the PDGF receptor and the c-kit receptor. Furthermore N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(2- methylbenzoyl)thiourea exhibited potent oral efficacy in in vivo assay using the rat carotid balloon injury model. Therefore, the quinoline and quinazoline-acylthiourea derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.
Synthesis and structure-activity relationship for new series of 4-phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase
Kubo, Kazuo,Ohyama, Shin-Ichi,Shimizu, Toshiyuki,Takami, Atsuya,Murooka, Hideko,Nishitoba, Tsuyoshi,Kato, Shinichiro,Yagi, Mikio,Kobayashi, Yoshiko,Iinuma, Noriko,Isoe, Toshiyuki,Nakamura, Kazuhide,Iijima, Hiroshi,Osawa, Tatsushi,Izawa, Toshio
, p. 5117 - 5133 (2007/10/03)
We discovered a new series of 4-phenoxyquinoline derivatives as potent and selective inhibitors of the platelet-derived growth factor receptor (PDGFr) tyrosine kinase. We researched the highly potent and selective inhibitors on the basis of both PDGFr and epidermal growth factor receptor (EGFr) inhibitory activity. First, we found a compound, Ki6783 (1), which inhibited PDGFr autophosphorylation at 0.13 μM, but it did not inhibit EGFr autophosphorylation at 100 μM. After extensive explorations, we found the two desired compounds, Ki6896 (2) and Ki6945 (3), which are substituted by benzoyl and benzamide at the 4-position of the phenoxy group on 4-phenoxyquinoline, respectively. These inhibitory activities were 0.31 and 0.050 μM, respectively, but neither of them inhibited EGFr autophosphorylation at 100 μM. We further investigated the profile of both compounds toward various tyrosine and serine/threonine kinases. The three compounds specifically inhibited PDGFr rather than the other kinases.
Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them
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, (2008/06/13)
Heterocyclylalkylpiperidine derivatives of general formula (I) in their enantiomeric or diastereoisomeric forms or mixtures of these forms, and/or, where appropriate, in their syn or anti form or a mixture thereof, as well as any salt thereof.
A synthesis of new pyrrolo[3,2-c]quinolines
Dudouit,Houssin,Henichart
, p. 755 - 758 (2007/10/03)
A synthesis of pyrrolo[3,2-c]quinolines substituted in the 7- and 8- positions by methoxy groups and in the 3- position by an amido group is described. The structures were designed to have a crescent shape, a planar fused cyclic moiety with two ortho methoxy groups and ionisable amino or aminidinic group at pH 7.
A synthesis of 4-quinolone-3-carboxylic acids via pyrolysis of N- aryldioxopyrrolines
Mohri, Kunihiko,Kanie, Akihiko,Horiguchi, Yoshie,Isobe, Kimiaki
, p. 2377 - 2384 (2007/10/03)
A synthesis of 4-quinolone-3-carboxylic acids (8) was achieved by pyrolysis of 4,5-dimethoxycarbonyl-1-aryl-1H-pyrrole-2,3-diones (3) followed by selective demethoxycarbonylation of the resulting 2,3-dimethoxycarbonyl-4- quinolones (4) in excellent overall yields.
A novel series of 4-phenoxyquinolines: Potent and highly selective inhibitors of PDGF receptor autophosphorylation
Kubo, Kazuo,Shimizu, Toshiyuki,Ohyama, Shin-Ichi,Murooka, Hideko,Nishitoba, Tsuyoshi,Kato, Shinichiro,Kobayashi, Yoshiko,Yagi, Mikio,Isoe, Toshiyuki,Nakamura, Kazuhide,Osawa, Tatsushi,Izawa, Toshio
, p. 2935 - 2940 (2007/10/03)
A novel series of 4-phenoxyquinolines some of which showed potent and highly selective inhibitory activities for PDGF receptor autophosphorylation, was discovered. Interestingly, their structures were very similar to those of the selective inhibitors for EGF receptor autophosphorylation.
HETEROCYCLIC HYDRAZIDE DERIVATIVES OF MONOCYCLIC BETA-LACTAM ANTIBIOTICS
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, (2008/06/13)
Antibacterial activity has been found in compounds of the formula. Compounds having the formula and pharmaceutically acceptable salts thereof, wherein: A is a bond or alkylene; Q completes a 5- or 6-membered saturated or unsaturated(including aromatic) heterocyclic ring having one or two, hetero atoms in the ring selected from nitrogen sulfur or oxygen; X is attached to an available carbon atom in the heterocyclic ring and is hydrogen or oxo; Y is attached to an available carbon atom in the heterocyclic ring and is hydrogen, amino, hydroxyl, halogen, carboxamide, nitrile, or carboxyl, except that Y is not carboxyl when the bicyclic ring completed by Q is 2-quinolyl, 3-quinolyl, or quinoxalyl; and the remaining symbols are as defined in the specification
2-oxo-1-[[(substituted sulfonyl)amino]-carbonyl]azetidines
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, (2008/06/13)
Antibacterial activity is exhibited by 3-acylamino-2-oxoazetidines having in the 1-position an activating group of the formula STR1 wherein R is STR2 and R4 is STR3
