283173-50-2

基本信息
盧卡帕尼
魯卡帕尼
瑞卡帕布堿
盧卡帕尼雜質(zhì)
盧卡帕尼雜質(zhì)16
瑞卡帕布/魯卡帕尼
8-氟-2-(4-((甲胺基)甲基)苯基)-4,5-二氫-1H-氮雜卓并[5,4,3-CD]吲哚-6(3H)-酮
8-氟-1,3,4,5-四氫-2-[4-[(甲基氨基)甲基]苯基]-6H-吡咯并[4,3,2-EF][2]苯并氮雜-6-酮
8-氟-1,3,4,5-四氫-2-[4-[(甲基氨基)甲基]苯基]-6H-吡咯并[4,3,2-EF][2]苯并氮雜卓-6-酮
AG014447
AG-14447
AG 014447
Rucaparib
PF-01367388
Rucaparib Base
AG 014447
AG014447
Rucaparib impurity
Rucaparib free base
物理化學(xué)性質(zhì)
常見問題列表
![methyl (4-(8-fluoro-1-oxo-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-5-yl)benzyl)(methyl)carbamate](/CAS/20180906/GIF/880160-69-0.gif)
880160-69-0

283173-50-2
以化合物(CAS: 880160-69-0)為原料合成8-氟-2-(4-((甲胺基)甲基)苯基)-4,5-二氫-1H-氮雜卓并[5,4,3-cd]吲哚-6(3H)-酮的一般步驟如下: 實(shí)施例13:合成8-氟-2-(4-甲氨基甲基-苯基)-1,3,4,5-四氫-氮雜環(huán)庚烷并[5,4,3-cd]吲哚-6-酮(15) 將內(nèi)酰胺14(14.42 g,0.038 mol)溶于氫溴酸的乙酸溶液(30%-32%,140 mL)中。反應(yīng)溶液在室溫下于500 mL燒瓶中攪拌46小時(shí),燒瓶與乙醇胺洗滌器系統(tǒng)連接。HPLC分析確認(rèn)反應(yīng)完成。向反應(yīng)溶液中加入冰(30 g),隨后緩慢加入NaOH水溶液(327 mL,10 M,3.27 mol),同時(shí)控制溫度在25℃至35℃之間。NaOH加入完成后,反應(yīng)混合物的pH值為10。過濾收集所得固體,用水(2×50 mL)洗滌。將濾餅懸浮于水(125 mL)中,攪拌2小時(shí)。再次過濾收集固體,用水(2×25 mL)洗滌并干燥,得到產(chǎn)物10.76 g,收率88%。 產(chǎn)物表征: 1H NMR(300 MHz, DMSO-d6)δ 2.577(s, 3H), 3.053(m, 2H), 3.406(m, 2H), 4.159(s, 2H), 7.36(dd, 1H, J = 2.4 Hz和J = 9.3 Hz), 7.44(dd, 1H, J = 2.4 Hz和J = 11.1 Hz), 7.63(d, 2H, J = 8.1 Hz), 7.70(d, 2H, J = 8.1 Hz), 8.265(t, 1H, J = 5.7 Hz), 11.77(s, 1H)。 計(jì)算值(C19H19FN3O)精確質(zhì)量:324.1512。實(shí)測值:324.1497。
參考文獻(xiàn):
[1] Patent: US2006/63926, 2006, A1. Location in patent: Page/Page column 6; 11
PARP-1 1.4 nM (Ki) |
Rucaparib is the most potent PARP inhibitor in enzyme assays (K i , 1.4 nM), and a possible?N-demethylation metabolite of AG14644. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.
Rucaparib and AG14584 significantly (P < 0.05) increases temozolomide toxicity. Rucaparib (1 mg/kg) significantly increases temozolomide-induced body weight loss.?Rucaparib (0.1 mg/kg) results in a 50% increase in the temozolomide-induced tumor growth delay. Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.