19798-80-2Relevant academic research and scientific papers
Synthesis and biological evaluation of novel 4-(2-fluorophenoxy)-2-(1h- tetrazol-1-yl)pyridines bearing semicarbazone moieties as potent antitumor agents
Qin, Mingze,Liao, Weike,Xu, Chen,Fu, Baolin,Ren, Jianguo,Gu, Yucheng,Gong, Ping
, p. 840 - 850 (2013)
A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their in vitro antitumor potency. Some of the compounds (10b, 10c, 10e-10h, 10m-10p, 10r, and 11b) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC-1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI-38. The most promising compound 10p (IC50 = 0.08, 0.36, 0.97 μM) was 45.1-, 6.1-, and 2.4-fold more active than sorafenib (IC50 = 3.61, 2.19, 2.32 μM), and 17, 3.2, and 2.9 times better than PAC-1 (IC50 = 1.36, 1.17, 2.83 μM) against three cancer cell lines (HT-29, H460, and MKN-45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase. A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their cytotoxic activities in vitro. The most promising compound 10p was further examined for enzymatic activity, with the goal to investigate the molecular mechanisms of action.
Synthesis method of imidazopyridine or pyrimidine derivative
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, (2021/05/29)
The invention belongs to the technical field of synthesis, and particularly relates to a synthesis method of an imidazopyridine or pyrimidine derivative. The imidazopyridine or pyrimidine compound is obtained by taking pyridine or pyrimidinecarboxylic acid as a synthon through amidation, Hofmann degradation and cyclization reaction, and the obtained imidazopyridine or pyrimidine derivative can be further converted to generate a functional product. The method has the advantages of easily available raw materials, simple operation, high reaction efficiency, convenient post-treatment, and diversity of functional groups.
Synthesis method of Tucatinib and intermediate product thereof
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, (2020/11/09)
The invention discloses a synthesis method of Tucatinib, and the method comprises the following step: carrying out substitution reaction on halate of a compound shown in a formula VI or free alkali thereof serving as a raw material and a compound shown in a formula VII under an alkaline condition to obtain a compound shown in a formula VIII. The raw materials used in the whole synthesis route areeasy to obtain, expensive catalysts are not needed, and the method is suitable for large-scale production and beneficial to industrial production of the Tucatinib.
Preparation method of 2-amino-4-fluoropyridine
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, (2018/09/12)
The invention discloses a preparation method of 2-amino-4-fluoropyridine, comprising the synthetic steps of 1, subjecting 2-pyridinecarboxylic acid as a raw material to reaction in the presence of thionyl chloride and a salt to obtain 4-chloropyridine-2-acyl chloride, and subjecting 4-chloropyridine-2-acyl chloride the presence of ammonia to obtain 4-chloropyridine-2-amide; 2, subjecting 4-chloropyridine-2-amide to Hofmann rearrangement reaction to obtain 2-amino-4-chloropyridine; 3, subjecting 2-amino-4-chloropyridine to halogen exchange to obtain 2-amino-4-fluoropyridine. The problems of theexisting preparation method, such as long synthetic path, operational complexity, high pollution of three wastes, poor atomic economy, low yield and high manufacture cost, are solved.
Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a structure-based core refining approach
Wang, Jun,Zhan, Peng,Li, Zhenyu,Liu, Huiqing,De Clercq, Erik,Pannecouque, Christophe,Liu, Xinyong
, p. 531 - 538 (2014/05/06)
As a continuation of our efforts to discover and develop back-up analogs of DAPYs, novel substituted nitropyridine derivatives were designed via a structure-based core refining approach, synthesized and evaluated for their in vitro HIV-1 activity in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against wild-type HIV-1 IIIB. Most notably, the compound 7b was identified as the most promising candidate in inhibiting HIV-1 replication with an EC 50 value of 0.056 μM and a selective index (SI) of 1251, which were much better than those of NVP (EC50 = 0.23 μM) and DLV (EC50 = 0.51 μM). Some other compounds, 7k, 7c, 7j and 7e, were also endowed with a favorable anti-HIV-1 potency (EC50 = 0.034, 0.11, 0.11 and 0.16 μM, respectively). Some antivirally active compounds also showed moderate inhibitory activity against RT. Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogs provide valuable avenues for future molecular optimization.
ANTIVIRAL DRUGS FOR TREATMENT OF ARENA VIRUS INFECTION
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Paragraph 0000228, (2013/08/28)
Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by the Arenavirus family such as Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever
Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles
Burgeson, James R.,Moore, Amy L.,Gharaibeh, Dima N.,Larson, Ryan A.,Cerruti, Natasha R.,Amberg, Sean M.,Hruby, Dennis E.,Dai, Dongcheng
, p. 750 - 756 (2013/02/25)
A series of potent arenavirus inhibitors sharing a benzimidazole core were previously reported by our group. SAR studies were expanded beyond the previous analysis, which involved the attached phenyl rings and methylamino linker portion, to include modifications focused on the benzimidazole core. These changes included the introduction of various substituents to the bicyclic benzimidazole ring system along with alternate core heterocycles. Many of the analogs containing alternate nitrogen-based bicyclic ring systems were found to retain antiviral potency compared to the benzimidazole series from which we derived our lead compound, ST-193. In fact, 21h, built on an imidazopyridine core, possessed a near tenfold increase in potency against Lassa virus pseudotypes compared to ST-193. As found with the benzimidazole series, broad-spectrum arenavirus activity was also observed for a number of the analogs discovered during this study.
METHOD OF INHIBITING HAMARTOMA TUMOR CELLS
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Page/Page column 22, (2012/08/28)
Dimorpholinopyrimidines are useful for inhibiting growth or proliferation of hamartoma tumor cells. Because the Dimorpholinopyrimidines inhibit the growth and proliferation of hamartoma tumor cells they are also useful in treating PTEN hamartoma tumor syndromes. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of dimorpholinopyrimidine derivative that is effective to inhibit growth or proliferation of the hamartoma tumor cells.
Identification of NVP-BKM120 as a potent, selective, orally bioavailable class i PI3 kinase inhibitor for treating cancer
Burger, Matthew T.,Pecchi, Sabina,Wagman, Allan,Ni, Zhi-Jie,Knapp, Mark,Hendrickson, Thomas,Atallah, Gordana,Pfister, Keith,Zhang, Yanchen,Bartulis, Sarah,Frazier, Kelly,Ng, Simon,Smith, Aaron,Verhagen, Joelle,Haznedar, Joshua,Huh, Kay,Iwanowicz, Ed,Xin, Xiaohua,Menezes, Daniel,Merritt, Hanne,Lee, Isabelle,Wiesmann, Marion,Kaufman, Susan,Crawford, Kenneth,Chin, Michael,Bussiere, Dirksen,Shoemaker, Kevin,Zaror, Isabel,Maira, Sauveur-Michel,Voliva, Charles F.
supporting information; experimental part, p. 774 - 779 (2011/12/03)
Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.
Synthesis and biological evaluation of piperazinyl heterocyclic antagonists of the gonadotropin releasing hormone (GnRH) receptor
Vera, Matthew D.,Lundquist IV, Joseph T.,Chengalvala, Murty V.,Cottom, Joshua E.,Feingold, Irene B.,Garrick, Lloyd M.,Green, Daniel M.,Hauze, Diane B.,Mann, Charles W.,Mehlmann, John F.,Rogers, John F.,Shanno, Linda,Wrobel, Jay E.,Pelletier, Jeffrey C.
supporting information; scheme or table, p. 2512 - 2515 (2010/07/06)
Antagonism of the gonadotropin releasing hormone (GnRH) receptor has resulted in positive clinical results in reproductive tissue disorders such as endometriosis and prostate cancer. Following the recent discovery of orally active GnRH antagonists based on a 4-piperazinylbenzimidazole template, we sought to investigate the properties of heterocyclic isosteres of the benzimidazole template. We report here the synthesis and biological activity of eight novel scaffolds, including imidazopyridines, benzothiazoles and benzoxazoles. The 2-(4-tert-butylphenyl)-8-(piperazin-1-yl)imidazo[1,2-a]pyridine ring system was shown to have nanomolar binding potency at the human and rat GnRH receptors as well as functional antagonism in vitro. Additional structure-activity relationships within this series are reported along with a pharmacokinetic comparison to the benzimidazole-based lead molecule.
