25710-23-0Relevant articles and documents
Discovery of new thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives as orally active phosphoinositide 3-kinase inhibitors
Sun, Yan,Fu, Rong,Lin, Songwen,Zhang, Jingbo,Ji, Ming,Zhang, Yan,Wu, Deyu,Zhang, Kehui,Tian, Hua,Zhang, Mingyi,Sheng, Li,Li, Yan,Jin, Jing,Chen, Xiaoguang,Xu, Heng
, (2021)
As abnormal PI3K signaling is a feature of many types of cancer, the development of orally active PI3K inhibitors is of great significance for targeted cancer therapy. Through integrating strategies of reducing aromatic character/increasing the fraction of sp3 carbons together with scaffold hopping, we designed and synthesized two new series of thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives for use as PI3K inhibitors. Our structure–activity relationship studies led to the identification of thieno[2,3-d]pyrimidine 6a and thiazolo[5,4-d]pyrimidine 7a, which exhibited remarkable nanomolar PI3K potency, good antiproliferative activity, favorable pharmacokinetic properties and significant in vivo anti-cancer efficacy. Notably, thiazolo[5,4-d]pyrimidine 7a had better anti-cancer activity than thieno[2,3-d]pyrimidine 6a and is worthy of further pre-clinical evaluation for its use in cancer treatment.
Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of Cryptococcus neoformans and Cryptococcus gattii
Donlin, Maureen J.,Lane, Thomas R.,Riabova, Olga,Lepioshkin, Alexander,Xu, Evan,Lin, Jeffrey,Makarov, Vadim,Ekins, Sean
supporting information, p. 774 - 781 (2021/05/04)
Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the Cryptococcus genus, Cryptococcus neoformans and Cryptococcus gattii. Eighty percent of cryptococcosis diseases are caused by C. neoformans that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using in vitro and computational machine learning approaches. These compounds can inhibit C. neoformans growth at submicromolar levels, are effective against fluconazole-resistant C. neoformans and a clinical strain of C. gattii, and are not antagonistic with currently approved antifungals.
