(2S,3R,4S,5R)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新 | 1219089-32-3

分子结构分类

有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类

中文名称

(2S,3R,4S,5R)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新

中文别名

——

英文名称

(2S,3R,4S,5R)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid

英文别名

(2S,3R,4S,5R)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cvano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid；L-Proline, 3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)-, (3R,4S,5R)-

(2S,3R,4S,5R)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新化学式

CAS

1219089-32-3

化学式

C₂₃H₂₂Cl₂F₂N₂O₂

mdl

——

分子量

467.343

InChiKey

IIEWBFYJGJATRB-YGLGAKQISA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

573.0±50.0 °C(Predicted)
密度：

1.37±0.1 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

3.5
重原子数：

31
可旋转键数：

5
环数：

3.0
sp3杂化的碳原子比例：

0.39
拓扑面积：

73.1
氢给体数：

2
氢受体数：

6

上下游信息

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxylic acid	1219086-89-1	C₂₃H₂₂Cl₂F₂N₂O₂	467.343
——	(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid ethylamide	1354693-54-1	C₂₅H₂₇Cl₂F₂N₃O	494.412
——	rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-carbamoyl-phenyl)-amide	——	C₃₀H₂₈Cl₂F₂N₄O₂	585.481
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester	1354693-41-6	C₃₁H₂₉Cl₂F₂N₃O₃	600.492
——	racemic 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino}benzoic acid t-butyl ester	——	C₃₄H₃₅Cl₂F₂N₃O₃	642.573
——	2-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-2-methyl-propionic acid methyl ester	1229705-37-6	C₃₄H₃₅Cl₂F₂N₃O₃	642.573
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-2-fluoro-benzoic acid methyl ester	1354693-43-8	C₃₁H₂₈Cl₂F₃N₃O₃	618.483
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino}-3-methoxybenzoic acid methyl ester	1229705-05-8	C₃₂H₃₁Cl₂F₂N₃O₄	630.519
——	(2RS,3SR,4RS,5SR)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethylpropyl)-pyrrolidine-2-carboxylic acid {1-[2-methyl-2-((R)-1-oxiranylmethoxy)-propyl]-1H-pyrazol-3-yl}-amide	——	C₃₃H₃₇Cl₂F₂N₅O₃	660.591
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-methyl-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid	1354692-56-0	C₃₂H₃₁Cl₂F₂N₃O₄	630.519
——	5-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-1H-indole-2-carboxylic acid ethyl ester	1229704-18-0	C₃₄H₃₂Cl₂F₂N₄O₃	653.556
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-methyl-pyrrolidine-2-carbonyl]amino}-3-methoxy-benzoic acid methyl ester	1354693-47-2	C₃₃H₃₃Cl₂F₂N₃O₄	644.546
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-prop-2-ynyl-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid	1354692-89-9	C₃₄H₃₁Cl₂F₂N₃O₄	654.541
——	rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-1-cyclopropylmethyl-5-(2,2-dimethyl-propyl)pyrrolidine-2-carboxylic acid {1-[2-methyl-2-((R)-1-oxiranylmethoxy)propyl]-1H-pyrazol-3-yl}amide	——	C₃₇H₄₃Cl₂F₂N₅O₃	714.683
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-((1R,2R)-2-ethoxycarbonyl-cyclopropylmethyl)pyrrolidine-2-carbonyl]amino}-3-methoxy-benzoic acid	1354692-98-0	C₃₈H₃₉Cl₂F₂N₃O₆	742.647
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-((1S,2S)-2-ethoxycarbonyl-cyclopropylmethyl)pyrrolidine-2-carbonyl]amino}-3-methoxy-benzoic acid	1354692-97-9	C₃₈H₃₉Cl₂F₂N₃O₆	742.647
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-((1R,2R)-2-methoxycarbonyl-cyclopropylmethyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid methyl ester	1354692-96-8	C₃₈H₃₉Cl₂F₂N₃O₆	742.647
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-((1S,2S)-2-methoxycarbonyl-cyclopropylmethyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid methyl ester	1354692-95-7	C₃₈H₃₉Cl₂F₂N₃O₆	742.647
——	4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-(2-ethoxycarbonyl-cyclopropylmethyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid methyl ester	1354692-88-8	C₃₉H₄₁Cl₂F₂N₃O₆	756.674

反应信息

作为反应物：

描述：

(2S,3R,4S,5R)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新在三乙酰氧基硼氢化钠、溶剂黄146 、 N,N-二异丙基乙胺、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下，以二氯甲烷为溶剂，反应 28.5h，生成 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-methyl-pyrrolidine-2-carbonyl]amino}-3-methoxy-benzoic acid methyl ester

参考文献：

名称：

N-SUBSTITUTED PYRROLIDINES

摘要：

描述了公式的化合物及其对映体和药用可接受的盐，以及含有该化合物及其药用可接受的盐的药物组合物，以及该化合物和药物组合物用于治疗、控制、改善或预防癌症的用途。

公开号：

US20120010235A1
作为产物：

描述：

(Z)-3-(3-氯-2-氟苯基)-2-(4-氯-2-氟苯基)-2-丙烯腈在 silver fluoride 、三乙胺、三氟乙酸作用下，以二氯甲烷为溶剂，反应 28.0h，生成 (2S,3R,4S,5R)-3-(3-氯-2-氟苯基)-4-(4-氯-2-氟苯基)-4-氰基-5-新

参考文献：

名称：

[EN] MDM2 DEGRADERS AND USES THEREOF
[FR] AGENTS DE DÉGRADATION DE MDM2 ET LEURS UTILISATIONS

摘要：

本发明涉及化合物和方法，通过本发明的化合物对小鼠双分子2同源蛋白（"MDM2"）蛋白进行泛素化和/或降解的调节。

公开号：

WO2021188948A1

点击查看最新优质反应信息

文献信息

Substituted Pyrrolidine-2-Carboxamides

申请人：Ding Qingjie

公开号：US20100075948A1

公开（公告）日：2010-03-25

There are provided compounds of the formula wherein X, Y, R 1 , R 2 , R 3 , R 3 , R 4 , R 5 , R 6 and R 7 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

提供了以下式的化合物其中X、Y、R1、R2、R3、R3、R4、R5、R6和R7如本文所述，以及其对映体和药用可接受的盐和酯。这些化合物可用作抗癌药物。
SUBSTITUTED HEXAHYDROPYRROLO[1,2-C]IMIDAZOLONES

申请人：Chu Xin-Jie

公开号：US20120065210A1

公开（公告）日：2012-03-15

There are provided compounds of formula I or a pharmaceutically acceptable salt thereof, wherein X, Y, R 1 , R 1′ , R 2 , R 2′ , R 3 , R 4 , R 5 are as defined herein. The compounds exhibit activity as anticancer agents.

提供的化合物具有以下式I的结构或其药学上可接受的盐，其中X，Y，R 1 ，R 1′ ，R 2 ，R 2′ ，R 3 ，R 4 ，R 5 如本文所定义。这些化合物表现出抗癌剂的活性。
MRNA-BASED GENE EXPRESSION FOR PERSONALIZING PATIENT CANCER THERAPY WITH AN MDM2 ANTAGONIST

申请人：Hoffmann-La Roche Inc.

公开号：US20150211073A1

公开（公告）日：2015-07-30

Use of at least an MDM2 gene panel, preferably a four gene MDM2 gene panel, as a biomarker for predicting the response to a MDM2 antagonist.

至少使用一个MDM2基因面板，最好是一个四基因MDM2基因面板，作为预测对MDM2拮抗剂反应的生物标志物。
[EN] SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES<br/>[FR] PYRROLIDINE-2-CARBOXAMIDES SUBSTITUÉS

申请人：HOFFMANN LA ROCHE

公开号：WO2010031713A1

公开（公告）日：2010-03-25

There are provided compounds of the formula (I) wherein X, Y, R1, R2, R3, R3, R4, R5, R6 and R7 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

提供了公式（I）的化合物，其中X，Y，R1，R2，R3，R3，R4，R5，R6和R7如本文所述，并提供其对映体和药学上可接受的盐和酯。这些化合物可用作抗癌剂。
Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

作者：Qingjie Ding、Zhuming Zhang、Jin-Jun Liu、Nan Jiang、Jing Zhang、Tina M. Ross、Xin-Jie Chu、David Bartkovitz、Frank Podlaski、Cheryl Janson、Christian Tovar、Zoran M. Filipovic、Brian Higgins、Kelli Glenn、Kathryn Packman、Lyubomir T. Vassilev、Bradford Graves

DOI：10.1021/jm400487c

日期：2013.7.25

Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.