183433-62-7Relevant articles and documents
Pyridine substituted chalcone type compound or medicinal salt thereof and preparation method and application thereof
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Paragraph 0103; 0106, (2019/04/10)
The invention discloses a pyridine substituted chalcone type compound with a structure as shown in a general formula I or a medicinal salt thereof, and also discloses a preparation method and application of the compound or the medicinal salt thereof. The compound or the medicinal salt thereof disclosed by the invention has small toxic or side effects and strong water solubility, is not easy to generate drug resistance, can effectively inhibit the aggregation of tubulin, has stronger anti-tumor activity in vitro and in vivo, can ensure more stable metabolism and has good pharmacological prospects. The invention also discloses combined application of the pyridine substituted chalcone type compound or the medicinal salt thereof and a TACC3 inhibitor for effectively inhibiting the activity oftumor cells resistant to tubulin.
Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents
Xu, Feijie,Li, Wenlong,Shuai, Wen,Yang, Limei,Bi, Yi,Ma, Cong,Yao, Hequan,Xu, Shengtao,Zhu, Zheying,Xu, Jinyi
, p. 1 - 14 (2019/04/17)
Further optimization of the trimethoxyphenyl scaffold of parent chalcone compound (2a) by introducing a pyridine ring afforded a series of novel pyridine-chalcone derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC50 values ranging from 0.023 to 0.045 μM against a panel of cancer cell lines. Further mechanism study results demonstrated that compound 16f effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Moreover, cellular mechanism studies disclosed that 16f caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Also, 16f reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 16f significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, which was stronger than the reference compound CA-4, indicating that it is worthy to investigate 16f as a potent microtubule-destabilizing agent for cancer therapy.
Synthesis of Functionalized Heteroaromatics: Application to Formal Total Synthesis of Camptothecin
Murata, Naoko,Sugihara, Takumichi,Kondo, Yoshinori,Sakamoto, Takao
, p. 298 - 300 (2007/10/03)
The formal total synthesis of camptothecin was achieved via two types of lithiation reactions of pyridine derivatives and a Pd-catalyzed carbonylation of pyridylmethyl methanesulfonates.
Practical asymmetric synthesis of (S)-4,ethyl-7,8-dihydro-4-hydroxy-1H- pyrano[3,4-f]indolizine-3,6,10(4H)-trione, a key intermediate for the synthesis of Irinotecan and other camptothecin analogs
Henegar,Ashford,Baughman,Sih,Gu
, p. 6588 - 6597 (2007/10/03)
A practical asymmetric synthesis of (S) 4-ethyl-7,8-dihydro-4-hydroxy- 1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6- methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.
