29335-36-2Relevant articles and documents
Process research towards a scalable synthesis of the muscarinic M 1 receptor subtype selective agonist MCD-386
Copp, Richard R.,Abraham, Brent D.,Farnham, James G.,Twose, Trevor M.
, p. 1344 - 1347 (2011)
An efficient process for the M1-selective muscarinic agonist MCD-386 has been developed that offers significant advantages over the original synthetic approach. The new process utilizes an improved preparation of a known symmetrical diamine ester, followed by elaboration to a symmetrical 5-substituted tetrahydropyrimidine. The new route avoids cryogenics and chromatography steps, circumvents an expensive protecting group strategy, and offers significant improvements in cost and throughput.
Optimization of Novel 1-Methyl-1 H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber's Pole Worm
Le, Thuy G.,Kundu, Abhijit,Ghoshal, Atanu,Nguyen, Nghi H.,Preston, Sarah,Jiao, Yaqing,Ruan, Banfeng,Xue, Lian,Huang, Fei,Keiser, Jennifer,Hofmann, Andreas,Chang, Bill C. H.,Garcia-Bustos, Jose,Jabbar, Abdul,Wells, Timothy N. C.,Palmer, Michael J.,Gasser, Robin B.,Baell, Jonathan B.
, p. 10875 - 10894 (2019/01/04)
A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 μM. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 μM. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 μM.
Substituted aminopyrimidine compounds and their method and use thereof
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Paragraph 1308; 1309, (2017/12/28)
The invention relates to a new aminopyrimidine compound and an application thereof as a drug for treating disorder or diseases related to PI3-kinase abnormity in a free form or a pharmaceutically acceptable salt and preparation form. The invention also relates to a pharmaceutical composition which contains the new aminopyrimidine compound and an application of the pharmaceutical composition in treating mammal disorder or diseases and especially treating human disorder or diseases related to the PI3-kinase abnormity, such as treatment of immunity and inflammatory diseases of PI3-kinase regulation which plays a leading role in a leucocyte function and treatment of proliferative diseases which are related to PI3-kinase activity and include but not limited to leukaemia and solid tumor.