摘要
<正>抗肿瘤药阿帕鲁胺(apalutamide,1)化学名称为 4-[7-(6-氰基-5-(三氟甲基)吡啶-3-基)-8-氧代-6-硫代-5,7-二氮杂螺[3.4]辛烷-5-基]-2-氟-N-甲基苯甲酰胺,分子式为 C21H15F4N5O2S,CAS 登记号为 956104-40-8。阿帕鲁胺是由强生公司研发的雄激素受体(androgen receptor,AR)拮抗剂,于 2018 年 2 月经美国 FDA 批准上市[1]。阿帕鲁胺选择性与
引文
[1] US FDA.FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint[EB/OL].[2018-02-14].https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm596768.htm.
[2] PANG X,WANG Y,CHEN Y.Design,synthesis,and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles[J].Bioorg Med Chem Lett,2017,27(12):2803-2806.
[3] SMITH M R,ANTONARAKIS E S,RYAN C J,et al.Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509),a potent androgen receptor antagonist,in the high-risk nonmetastatic castration-resistant prostate cancer cohort[J].Eur Urol,2016,70(6):963-970.
[4] CLEGG N J,WONGVIPAT J,JOSEPH J,et al.ARN-509:a novel anti-androgen for prostate cancer treatment[J].Cancer Res,2012,72(6):1494-1503.
[5] JUNG M E.Androgen receptor modulator for the treatment of prostate cancer and androgen receptor associated diseases:EP,2656841 A[P].2007-03-27.
[6] JUNG M E,OUK S,YOO D,et al.Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC)[J].J Med Chem,2010,53(7):2779-2796.
[7] 陈元伟,龚瑜.咪唑二酮类化合物及其用途:中国,104211683 A[P].2014-12-17.
[8] 迈克尔·E·琼,查尔斯·L·索耶斯,塞梅蒂·乌克,等.用于治疗前列腺癌和与雄激素受体相关的疾病的雄激素受体调节剂:中国,101454002 B[P].2011-06-08.
[9] 尼古拉斯·D·史密斯,赛琳·博纳富斯,贾卡林·D·朱利安.雄激素受体调节剂及其用途:中国,102884057 B[P].2016-09-14.
[10] OUATHEK O,ANNA D,GUANGBIN Y,et al.Synthesis of thiohydantions:US,2015/0191449 A[P].2015-07-09.
[11] HAIM C B,HORVATH A,WEERTS E E.Process for the preparation of a diarylthiohydantoin compound:WO,2016/100652 A[P].2016-06-23.