571188-59-5Relevant articles and documents
Copper-catalyzed selective C-N bond formation with 2-amino, 2-hydroxy and 2-bromo-5-halopyridine
Roy, Swarnali,Paul, Barnali,Mukherjee, Ayan,Kundu, Biswajit,Talukdar, Arindam
, p. 44366 - 44370 (2017)
A copper-catalyzed 1,2-diol amination at the electron-rich C-5 position of unprotected 2-amino/2-hydroxy-5-halopyridine provided excellent yields. Selective amination preferably at C-5 in 2-bromo-5-iodopyridine was achieved under the same conditions. The selective, generally mild and economical coupling reaction at C-5 position described herein could be achieved with amines, heterocycles and amides.
Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma
Yuan, Kai,Kuang, Wenbin,Chen, Weijiao,Ji, Minghui,Min, Wenjian,Zhu, Yasheng,Hou, Yi,Wang, Xiao,Li, Jiaxing,Wang, Liping,Yang, Peng
, (2021/12/09)
Multiple myeloma (MM) ranks second in malignant hematopoietic cancers, and the most common anti-MM drugs easily generate resistance. CDK4/6 have been validated to play determinant roles in MM, but no remarkable progress has been obtained from clinical trials of CDK4/6 inhibitors for MM. To discover novel CDK6 inhibitors with better potency and high druggability, structure-based virtual screening was conducted to identify compound 10. Further chemical optimization afforded a better derivative, compound 32, which exhibited strong inhibition of CDK4/6 and showed high selectivity over 360+ kinases, including homologous CDKs. The in vivo evaluation demonstrated that compound 32 possessed low toxicity (LD50 > 10,000 mg/kg), favorable bioavailability (F% = 51%), high metabolic stability (t1/2 > 24 h) and strong anti-MM potency. In summary, we discovered a novel CDK4/6 inhibitor bearing favorable drug-like properties and offered a great candidate for MM preclinical studies.
Azaindole pyrimidinamine heterocyclic compound as well as preparation method and application thereof
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, (2021/08/14)
The invention discloses an azaindole pyrimidinamine heterocyclic compound as well as a preparation method and application thereof. The compound is shown as a formula (S). The compound provided by the invention can inhibit malignant proliferation of cancers, has good treatment effect, low toxicity and good drug metabolism characteristics, is not easy to generate drug resistance, and can be used for preparing drugs for treating cancers or tumor-related diseases. The cancers or tumor-related diseases include multiple myeloma, leukemia, breast cancer, prostate cancer, lung cancer, liver cancer, gastric cancer, bone cancer, brain cancer, head and neck cancer, intestinal cancer, pancreatic cancer, bladder cancer, testicular cancer, ovarian cancer and endometrial cancer.
Industrial preparation method 4 - (6 - amino-pyridin -3 -yl) piperazine -1 - carboxylic acid tert-butyl ester
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, (2021/11/14)
The method adopts 4 - bromo 6 - nitropyridine and piperazine as a starting raw material to prepare high-purity -3 - (-1 -nitropyridine 5 -yl) piperazine -2 - carboxylic acid as a catalyst through nucleophilic substitution reaction in the presence of an organic solvent and water. 1 - (6 - aminopyrid -3 -yl) piperazine is prepared by using an acid as a catalyst in a mixed solvent of an alcohol organic solvent and water to obtain high-purity Boc (4 -aminopyridine 6 -1 -yl) piperazine-3 -carboxylic acid tert-butyl ester. Shallow color 4 - (6 - aminopyrid -3 -yl) piperazine -1 - carboxylic acid tert-butyl ester. The method is simple and convenient to operate, less in environmental pollution, high in yield, low in cost, good in product quality and more suitable for industrial production.