62981-82-2Relevant articles and documents
2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase
Gangjee, Aleem,Mavandadi, Farahnaz,Kisliuk, Roy L.,McGuire, John J.,Queener, Sherry F.
, p. 4563 - 4568 (1996)
Six novel 2-amino-4-oxo-5-[(substituted phenyl)sulfanyl]pyrrolo[2,3- d]pyrimidines 7-12 were synthesized as potential inhibitors of thymidylate synthase (TS) and as antitumor and/or antibacterial agents. The analogues contain a 5-thio substituent with a p
Discovery of AS-1763: A Potent, Selective, Noncovalent, and Orally Available Inhibitor of Bruton's Tyrosine Kinase
Asami, Tokiko,Furuichi, Hatsuo,Irie, Takayuki,Kashimoto, Shigeki,Kawahata, Wataru,Kiyoi, Takao,Sawa, Masaaki
, p. 14129 - 14141 (2021/10/01)
Although Bruton's tyrosine kinase (BTK) has been recognized as a validated drug target for the treatment of B-cell malignances, the emergence of clinical resistance to the first-generation covalent BTK inhibitors is becoming a serious concern. As a part of our effort to develop noncovalent BTK inhibitors, a series of novel pyrrolopyrimidines was identified as noncovalent inhibitors of both the wild-type and C481S mutant BTKs. Subsequent lead optimization led to the identification of an orally available, potent, and selective BTK inhibitor 13f (AS-1763) as a next-generation noncovalent BTK inhibitor. With significant efficacies in vivo tumor xenograft models, AS-1763 has advanced to phase 1 clinical trials.
Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold
Gao, Ling-Jie,Schwed, J. Stephan,Weizel, Lilia,De Jonghe, Steven,Stark, Holger,Herdewijn, Piet
, p. 132 - 137 (2013/02/23)
Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH4R (Ki = 0.5 μM), its lacks selectivity with a K i value for the hH3R of 1 μM. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show Ki values of less than 1 μM at the hH4R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH4R ligands.
Synthesis of new pyrrolo[2,3-d]pyrimidine derivatives and evaluation of their activities against human colon cancer cell lines
Tangeda, Saritha Jyostna,Garlapati, Achaiah
experimental part, p. 1453 - 1458 (2010/06/12)
New pyrrolo[2,3-d]Pyrimidines with heteroaryl substitution at 5th position through sulfur linker were synthesized incorporating putative pharmacophoric moieties like benzimidazole and benzothiazole as heteroaryl groups. Cytotoxic effect of all the compounds was carried out on HCT116 colon cancer cell lines. Compounds 6c and 6h with nitrobenzimidazole and pyrimidyl heterocycles attached at 5th position via sulfur were the most potent of all with IC50 values ≈17.6?μM. Among the four compounds tested for apoptosis induction activity, 6c induced apoptosis in a dose dependent manner.