title: Synthesis and evaluation of biological and antitumor activities of 5,7-dimethyl- oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives as novel inhibitors of FGFR1.
abstract: A series of 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives, N5a-5l, was designed, synthesized and evaluated for their FGFR1-inhibition ability as well as cytotoxicity against three cancer cell lines (H460, B16F10 and A549) in vitro. Several compounds displayed good-to-excellent potency against these cancer cell lines compared to SU5402. Structure-activity relationship analyses indicated that compounds with a rigid structure and more heteroatoms at the side chain of the parent ring were more effective than those without these substitutions. The compound N5g (37.4% FGFR1 inhibition at 1.0 μM) was identified to have the most potent antitumor activities, with IC50 values of 5.472, 4.260 and 5.837 μM against H460, B16F10 and A549 cell lines, respectively. Together, our results suggest that 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives may serve as potential agents for the treatment of FGFR1-mediated cancers.
authors: a School of Pharmacy, Health Science Center Xi'an Jiaotong University , Xi'an , China and.|b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Faqing
authors: F
authors: Ye
authors: b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Yuewu
authors: Y
authors: Wang
authors: b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Siyun
authors: S
authors: Nian
authors: b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Yu
authors: Y
authors: Wang
authors: b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Di
authors: D
authors: Chen
authors: b School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou , China.
authors: Shufang
authors: S
authors: Yu
authors: a School of Pharmacy, Health Science Center Xi'an Jiaotong University , Xi'an , China and.
authors: Sicen
authors: S
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000608074:2-(4-methyl-1-phenylpent-1-en-1-yl)-5,7-dimethyl-4H-oxazolo(5,4-d)pyrimidine-4,6-(5H,7H)-dione; D000970:Antineoplastic Agents; D010080:Oxazoles; D011743:Pyrimidines; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Cancer therapy; FGFR1; kinase inhibitor; structure–activity relationship; synthesis