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闃挎柉鍒╁悍鍗靛发鐧岃瘯楠岃嵂鐗╁ゥ鎷夊笗灏?Olaparib, 銈?儵銉戙儶銉?鐨勫寲瀛﹀悎鎴
2015-05-10 07:14:08

Synthesis of Ovarian Cancer Drug Olaparib_Lynparza_PAPP Inhibitor_AstraZeneca 闃挎柉鍒╁悍鍗靛发鐧岃瘯楠岃嵂鐗╁ゥ鎷夊笗灏?Olaparib,銈?儵銉戙儶銉?鐨勫寲瀛﹀悎鎴怽

Trade Name:Lynparza
Generic Name: Olaparib, 銈?儵銉戙儶銉?/span>
Synonym: AZD2281; KU-0059436
Chinese Name: 濂ユ媺甯曞凹
Chemical Name:4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H) phthalazin-1-one
CAS Number:763113-22-0
Mechanism of Action:Poly(ADP-ribose) polymerase inhibitors
Indication: Ovarian cancer
Date of Approval:December 19, 2014 (US), December 18, 2014 (EU)
Originator:KuDOS Pharmaceuticals
Developer: AstraZeneca

鏂拌?鍗靛罚銇屻倱娌荤檪钖?偑銉┿儜銉?儢

绫抽?鍝佸尰钖?搧灞?紙FDA锛夈伅12鏈?9鏃ャ?鑻便偄銈广儓銉┿偧銉嶃偒锛圓Z锛夈伄PARP锛堛儩銉狝DP-銉?儨銉笺偣鍚堟垚閰电礌锛夐樆瀹冲墹Lynparza锛堛偑銉┿儜銉?銉栵級銈払RCA閬轰紳瀛愬?鐣伴櫧鎬с伄閫茶?鍗靛罚銇屻倱銇?仼蹇溿仹鎵胯獚銇椼仧銆傘伨銇熴?浣点仜銇︺?鍚屽墹銇?偝銉炽儜銉嬨偑銉炽兓銉?偆銈?偘銉庛偣銉嗐偅銈?偣銇с亗銈?BRACAnalysisCDx銈傛壙瑾嶃仐銇熴?銈?儵銉戙儶銉栥伄閬╁繙銇??BRCA閬轰紳瀛愭瑺鎼嶃伄銇傘倠鍓嶆不鐧傛?銈掓寔銇ら?琛屽嵉宸c亴銈撱仹銇傘倠銆侭RCA閬轰紳瀛愩伅銆佹悕鍌枫仌 銈屻仧DNA銇?慨寰┿伀闁?笌銇椼?閫氬父銆佽叓鐦嶃伄鎴愰暦銈掓姂鍒躲仚銈嬨?BRCA閬轰紳瀛愭瑺鎼嶃倰銈傘仧銈夈仚鍚岄伜浼濆瓙澶夌暟銇?コ鎬с伅鍗靛罚銇屻倱銇?仾銈娿倓銇欍亸銆佸嵉宸c亴銈撴偅鑰呫伄鍏ㄤ綋銇?10%锛?5%銇?伜浼濇?銇瓸RCA澶夌暟銇?枹涓庛仐銇︺亜銈嬨仺銇裤倝銈屻倠銆?/p>

闃挎柉鍒╁悍鍗靛发鐧岃嵂鐗㎜ynparza(濂ユ媺甯曞凹,olaparib)

Lynparza锛坥laparib锛夋槸涓??棣栧垱鍙f湇澶氳仛ADP鏍哥硸鑱氬悎閰讹紙PARP锛夋姂鍒跺墏锛屽埄鐢―NA淇??閫斿緞鐨勭己闄凤紝浼樺厛鏉??鐧岀粏鑳炪?鐩?墠锛岄樋鏂?埄搴锋?寮?睍澶氫釜III鏈熺爺绌讹紝璋冩煡olaparib鐢ㄤ簬BRCA绐佸彉鍗靛发鐧屻?鑳冪檶銆佷钩鑵虹檶鐨勬不鐤椼?

Sources:

Jonathan Ledermann,Philipp Harter,Charlie Gourley,Michael Friedlander et al. Lancet Oncol. 2014;15:852-861

Bella Kaufman,Ronnie Shapira-Frommer,Rita K. Schmutzler,M. William Audeh,Susan M. Domchek et al.,Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation 锛孞 Clin Oncol. Published online November 3, 2014 锛?cite style="border: 0px; margin: 0px; padding: 0px; vertical-align: baseline; background: transparent;">JCO.2014.56.2728 锛?

Martin, Niall Morrison Barr et al,Preparation of phthalazinones as PARP inhibitors,PCT Int. Appl., WO2004080976

Menear, Keith Allan et al,Preparation of 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one and its crystal forms as PARP-1 inhibitors,PCT Int. Appl., WO2008047082

Menear, Keith A. et al.4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1,Journal of Medicinal Chemistry, 51(20), 6581-6591; 2008

Lou, Xi-yu; Yang, Xuan; Ding, Yi-li; Wang, Jian-jun; Yan, Qing-yan; Huang, Xian-gui; Guo, Yang-hui; Wang, Xiang-jing; Xiang, Wen-sheng, Synthesis of Olaparib derivatives and their antitumor activities, Chemical Research in Chinese Universities (2013), 29(2), 231-235.

The Phase II study for Olaparib was published in N Engl J Med 2012; 366:1382-1392 .by Jonathan Ledermann et al, titled “Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer”

Jose Lutzky, A phase 1 study of MEDI4736, an anti–PD-L1 antibody, in patients with advanced solid tumors. American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, June 3, 2014, Abstract 3001

Neil Howard Segal, Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody, American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, June 3, 2014, Abstract 3002


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