137281-23-3
137281-23-3 結(jié)構(gòu)式
基本信息
N-[4-[2-(2-氨基-4,7-二氫-4-氧代-1H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲?；鵠-L-谷氨酸二鈉鹽
培美曲塞二鈉鹽
Pemetrexed99%
PeMetrexed-13C5
PeMetrexed-15C5
PEMETREXED ACID
Premetred disodium
PEFLOXACINMESYLATE
Pemetrexed Hydrate
Pemetrexed disodium
N-[4-[2-(2-Amino-4,7
PeMetrexed disodiuM INT-6
Pemetrexed - Labeled 15N,13C5
The sour sour of the United States
N-(4- 2-(2-AMino-4,7-Dihydro-4-oxo-1H-pyrrol...
N-[4-[2-(2-AMino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]-L-glutaMic acid
(S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo-[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedi
N-(4-[2-(2-Amino-4,7-Dihydro-4-oxo-1H-pyrrolo)[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-Gluamic Acid
L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-
(S)-2-(4-(2-(2-AMino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl)benzaMido)pentanedioic acid
(S)-2-(4-(2-(2-AMino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl)benzaMido)pentanedioic acid
(2R)-2-{[4-(2-{2-aMino-4-oxo-1H,4H,7H-pyrrolo[2,3-d]pyriMidin-5-yl}ethyl)phenyl]forMaMido}pentanedioic acid
N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt
N-[4-[2-(2-aMino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyriMidin-5-yl)ethyl]benzoyl]L-GlutaMic acid (PeMetrexed acid)
物理化學(xué)性質(zhì)
安全數(shù)據(jù)
常見問題列表
![N-[4-[2-(2-氨基-4,7-二氫-4-氧代-1H-吡咯并[2,3-D]嘧啶-5-基)乙基]苯甲酰]-L-谷氨酸二乙酯對(duì)甲苯磺酸鹽](/CAS/GIF/165049-28-5.gif)
165049-28-5
137281-23-3
以(S)-2-(4-(2-(2-氨基-4-氧代-4,7-二氫-3H-吡咯并[2,3-d]嘧啶-5-基)乙基)苯甲酰胺基)戊二酸二乙酯 4-甲基苯磺酸鹽為原料合成培美曲塞二鈉鹽的一般步驟如下： 1. 培美曲塞二酸的制備（式2）： a. 在反應(yīng)器中加入1L的1N NaOH水溶液，冷卻至5-15℃。 b. 向冷卻的NaOH溶液中緩慢加入143g實(shí)施例1中制備的式3化合物，保持溫度在5-15℃。 c. 在5-15℃下攪拌反應(yīng)混合物2小時(shí)，隨后進(jìn)行過濾（HPLC純度：99.8%）。 d. 向?yàn)V液中加入2L EtOH，然后在5-15℃下緩慢滴加2N HCl水溶液，調(diào)節(jié)pH至3.0。 e. 將形成的結(jié)晶混合物在40-50℃下攪拌1小時(shí)，然后在40℃下過濾。 f. 用2L純水洗滌過濾產(chǎn)物，接著用1L EtOH洗滌。 g. 將洗滌后的產(chǎn)物溶解于4L EtOH/純水（1:1，v/v）中，在40-50℃下攪拌1小時(shí)。 h. 冷卻至室溫后過濾，用2L純水洗滌，再用1L EtOH洗滌。 i. 將產(chǎn)物在40-45℃下真空干燥16小時(shí)，得到88g培美曲塞二酸，為白色固體（產(chǎn)率：95%，HPLC純度：99.9%，個(gè)別雜質(zhì)含量：未提及）。
參考文獻(xiàn)：
[1] Patent: US2016/214987, 2016, A1. Location in patent: Paragraph 0081
[2] Patent: US2008/45711, 2008, A1. Location in patent: Page/Page column 11
Ki: 1.3 nM (TS), 7.2 nM (DHFR), 65 nM (GARFT)
Pemetrexed (LY231514) disodium is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) is one of the best substrates that is known for the enzyme FPGS (K m =1.6 μM and V max /K m =621). It is likely that polyglutamation and the polyglutamated metabolites of LY231514 play profound roles in determining both the selectivity and the antitumor activity of this novel agent. Whereas LY23l5l4 only moderately inhibits TS (K i =340 nM, recombinant mouse), the pentaglutamate of LY23l5l4 is 100-fold more potent (K i =3.4 nM), making LY231514 one of the most potent folate-based TS inhibitors.
The group of mice treated with PC61 plus Pemetrexed demonstrates statistically longer survival than other groups. In a survival analysis, significantly better survival is observed in the group of mice treated with PC61 plus Pemetrexed compare with those treated with PC61 alone, rat IgG plus Pemetrexed, or no treatment.