13438-65-8Relevant academic research and scientific papers
Discovery of novel dual extracellular regulated protein kinases (Erk) and phosphoinositide 3-kinase (pi3k) inhibitors as a promising strategy for cancer therapy
Guan, Zhe,Huang, Lei,Ju, Qiurong,Li, Yin,Sun, Jinjin,Wang, Shuping,Wu, Shiqi,Xu, Yungen,Zhang, Lingzhi,Zhu, Qihua
, (2021/06/14)
Concomitant inhibition of MAPK and PI3K signaling pathways has been recognized as a promising strategy for cancer therapy, which effectively overcomes the drug resistance of MAPK signaling pathway-related inhibitors. Herein, we report the scaffold-hopping generation of a series of 1H-pyrazolo[3,4-d]pyrimidine dual ERK/PI3K inhibitors. Compound 32d was the most promising candidate, with potent inhibitory activities against both ERK2 and PI3Kα which displays superior anti-proliferative profiles against HCT116 and HEC1B cancer cells. Meanwhile, compound 32d possessed acceptable pharmacokinetic profiles and showed more efficacious anti-tumor activity than GDDC-0980 and the corresponding drug combination (BVD-523 + GDDC-0980) in HCT-116 xenograft model, with a tumor growth inhibitory rate of 51% without causing observable toxic effects. All the results indicated that 32d was a highly effective anticancer compound and provided a promising basis for further optimization towards dual ERK/PI3K inhibitors.
POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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Page/Page column 103; 104, (2018/07/29)
The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors
Zhang, Han,Liu, Huan,Luo, Xiao,Wang, Yuxi,Liu, Yuan,Jin, Hongwei,Liu, Zhenming,Yang, Wei,Yu, Peilin,Zhang, Liangren,Zhang, Lihe
, p. 235 - 252 (2018/05/09)
Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cationic channel, plays critical roles in insulin release, cytokine production, body temperature regulation and cell death as a reactive oxygen species (ROS) and temperature sensor. However, few TRPM2 inhibitors have been reported, especially TRP-subtype selective inhibitors, which hampers the investigation and validation of TRPM2 as a drug target. To discover novel TRPM2 inhibitors, 3D similarity-based virtual screening method was employed, by which 2,3-dihydroquinazolin-4(1H)-one derivative H1 was identified as a TRPM2 inhibitor. A series of novel 2,3-dihydroquinazolin-4(1H)-one derivatives were subsequently synthesized and characterized. Their inhibitory activities against the TRPM2 channel were evaluated by calcium imaging and electrophysiology approaches. Some of the compounds exhibited significant inhibitory activity, especially D9 which showed an IC50 of 3.7 μM against TRPM2 and did not affect the TRPM8 channel. The summarized structure-activity relationship (SAR) provides valuable insights for further development of specific TRPM2 targeted inhibitors.
Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1D Adrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-g
Sakauchi, Nobuki,Kohara, Yasuhisa,Sato, Ayumu,Suzaki, Tomohiko,Imai, Yumi,Okabe, Yuichi,Imai, Shigemitsu,Saikawa, Reiko,Nagabukuro, Hiroshi,Kuno, Haruhiko,Fujita, Hisashi,Kamo, Izumi,Yoshida, Masato
, p. 2989 - 3002 (2016/05/19)
A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- and α1B-AR through scre
2-Aminomethylphenylamine as a novel scaffold for factor Xa inhibitor
Mochizuki, Akiyoshi,Nagata, Tsutomu,Kanno, Hideyuki,Suzuki, Makoto,Ohta, Toshiharu
experimental part, p. 1623 - 1642 (2011/04/21)
We have been researching orally active factor Xa inhibitor for a long time. We explored the new diamine linker using effective ligands to obtain a new attractive original scaffold 2-aminomethylphenylamine derivative. Compound 1D showed very strong in vitro and in vivo factor Xa inhibitory activity, as well as favorable PK profiles in po administration to monkeys.
Synthesis of new series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones for their bacterial and cyclin-dependent kinases (CDKs) inhibitory activities
Geffken, Detlef,Soliman, Raafat,Soliman, Farid S.D.,Abdel-Khalek, Magdi M.,Issa, Doaa A.E.
experimental part, p. 408 - 420 (2012/04/04)
Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4- ones were designed, synthesised, and evaluated for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine- 3,4-dione (3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2- Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido [2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans.
PYRIDINE DERIVATIVE SUBSTITUTED BY HETEROARYL RING, AND ANTIFUNGAL AGENT COMPRISING THE SAME
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Page/Page column 78, (2009/06/27)
The present invention provides an antifungal agent that has excellent antifungal action, and is also excellent in terms of its properties, safety, and metabolic stability. The present invention discloses a compound represented by the following formula I or a salt thereof, and an antifungal agent comprising the compound or the salt: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6-alkoxy-C1-6-alkyl group; R2 represents a hydrogen atom or an amino group; X, Y, Z, and W independently represent a nitrogen atom, an oxygen atom, a sulfur atom, or -CH-, provided that at least two among X, Y, and W are nitrogen atoms; the ring A represents a 5- or 6-membered heteroaryl ring or a benzene ring; Q represents a methylene group, an oxygen atom, -CH2O-, -OCH2-, -NH-, -NHCH2-, or -CH2NH-; and R3 represents a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, or a 5- or 6-membered heteroaryl group, each of which may have one or two substituents.
Novel pyridopyprimidinone derivatives which are HM74A agonists
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Page/Page column 19, (2008/06/13)
The invention is concerned with novel pyridopyrimidinone derivatives of formula (I): wherein R1 to R8, X, Y, m and n are as defined in the description and in the claims. The compounds of the present invention are HM74A agonists with
Pyrido[2,3-d]pyrimidine derivatives: Synthesis via the intermolecular aza-Wittig reaction/heterocyclization and the crystal structure
Okawa, Tomohiro,Toda, Mieko,Eguchi, Shoji,Kakehi, Akikazu
, p. 1467 - 1475 (2007/10/03)
Pyrido[2,3-d]pyrimidine derivatives 5 were synthesized by the intermolecular aza-Wittig reaction of 2- (triphenylphosphoranylidene)aminonicotinamides 3 derived from 2- aminonicotinic acid (1), with carboxylic acid chloride followed by heterocyclization vi
