2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyanopyrrole-1-carboxylic acid tert-butyl ester | 304853-97-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyanopyrrole-1-carboxylic acid tert-butyl ester
• 英文别名: 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo [d] [1,3] oxazin-6-yl)-5-cyano-pyrrole-1-carboxylic acid tert-butyl ester；2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyano-pyrrole-1-carboxylic acid tert-butyl ester；tert-butyl 2-cyano-5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-1-carboxylate；tert-butyl 2-cyano-5-(4,4-dimethyl-2-oxo-1H-3,1-benzoxazin-6-yl)pyrrole-1-carboxylate
• CAS: 304853-97-2
• 化学式: C₂₀H₂₁N₃O₄
• 分子量: 367.404
• InChiKey: HBHOVRSSGAOTRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyanopyrrole-1-carboxylic acid tert-butyl ester 反应 0.33h， 以37%的产率得到5-(4,4-dimethyl-2-oxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-2-carbonitrile
  参考文献：
  名称：

  [18F]氟甲基-Tanaproget衍生物的合成及其对孕酮受体表达成像的临床前评价

  摘要：

  雌激素受体（ER）和孕激素受体（PR）在约50％的乳腺癌病变中过表达，并用作生物标记物以对患者进行内分泌治疗。目前，免疫组化（IHC）评估...

  DOI：

  10.1039/c6ra07404a
• 作为产物：
  描述：

  1-吡咯甲酸叔丁酯 在 盐酸 、 四(三苯基膦)钯 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 17.5h， 生成 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyanopyrrole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Novel 6-Aryl-1,4- dihydrobenzo[d][1,3]oxazine-2-thiones as Progesterone Receptor Modulators Leading to the Potent and Selective Nonsteroidal Progesterone Receptor Agonist Tanaproget

  摘要：

  Tanaproget represents a potential first-in-class nonsteroidal PR agonist for contraception with improved safety and side effect profiles versus currently available steroidal oral contraceptives. Additional SAR, biological activity, and structural information from a tanaproget/hPR-LBD (hPR-LBD human progesterone receptor ligand binding domain) cocrystal structure will also be presented.

  DOI：

  10.1021/jm050358b

文献信息

• Cyanopyrroles
  申请人：American Home Products Corporation

  公开号：US20020068735A1

  公开（公告）日：2002-06-06

  This invention provides a progesterone receptor antagonist of formula 1 having the structure 1 wherein T is O, S, or absent; R 1 , and R 2 are each, independently, hydrogen, alkyl, substituted alkyl; or R 1 and R 2 are taken together form a ring and together contain —CH 2 (CH 2 ) n CH 2 —, —CH 2 CH 2 CMe 2 CH 2 CH 2 —, —O(CH 2 ) p CH 2 —, —O(CH 2 ) q O—, —CH 2 CH 2 OCH 2 CH 2 —, or —CH 2 CH 2 NR 7 CH 2 CH 2 —; n=1-5; p=1-4; q=1-4; R 3 is hydrogen, OH, NH 2 , alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR A ; R A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 4 is hydrogen, halogen, CN, NH 2 , alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 5 is hydrogen, alkyl, or substituted alkyl; R 6 is hydrogen, alkyl, substituted alkyl, or COR B , R B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R 7 is hydrogen or alkyl; or a pharmaceutically acceptable salt thereof

  这项发明提供了一种具有结构的孕酮受体拮抗剂 1 其中T为O、S或不存在；R 1 和R 2 分别为氢、烷基、取代烷基；或R 1 和R 2 一起形成一个环，并且一起含有—CH 2 (CH 2 ) n CH 2 —、—CH 2 CH 2 CMe 2 CH 2 CH 2 —、—O(CH 2 ) p CH 2 —、—O(CH 2 ) q O—、—CH 2 CH 2 OCH 2 CH 2 —或—CH 2 CH 2 NR 7 CH 2 CH 2 —； n=1-5；p=1-4；q=1-4； R 3 为氢、OH、NH 2 、烷基、取代烷基、烯基、取代烯基、炔基、取代炔基或COR A ； R A 为氢、烷基、取代烷基、烷氧基、取代烷氧基、氨基烷基或取代氨基烷基； R 4 为氢、卤素、CN、NH 2 、烷基、取代烷基、烷氧基、取代烷氧基、氨基烷基或取代氨基烷基； R 5 为氢、烷基或取代烷基； R 6 为氢、烷基、取代烷基或COR B ， R B 为氢、烷基、取代烷基、烷氧基、取代烷氧基、氨基烷基或取代氨基烷基； R 7 为氢或烷基；或其药学上可接受的盐
• Cyclic regimens utilizing indoline derivatives
  申请人：WYETH

  公开号：US20030050288A1

  公开（公告）日：2003-03-13

  This invention relates to cyclic combination therapies and regimens utilizing substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure: 1 wherein R 1 and R 2 may be single substituents or fused to form spirocyclic rings, in combination with progestins, estrogens, or both. These methods of treatment may be used for contraception, for the treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, or prostate, minimization of side effects, cyclic menstrual bleeding, or stimulation of food intake.

  本发明涉及使用取代的吲哚啉衍生物化合物作为孕激素受体拮抗剂，其具有以下一般结构式：1其中R1和R2可以是单个取代基或融合形成螺环，并与孕激素、雌激素或两者结合使用的循环组合疗法和方案。这些治疗方法可用于避孕、治疗和/或预防继发性闭经、功能性出血、子宫平滑肌瘤、子宫内膜异位症、多囊卵巢综合症、子宫内膜、卵巢、乳腺、结肠或前列腺的癌症和腺癌、减少副作用、循环月经出血或刺激食欲。
• Indoline derivatives
  申请人：Wyeth

  公开号：US20030220388A1

  公开（公告）日：2003-11-27

  This invention relates to substituted indoline derivative compounds which are antagonists of the progesterone receptor, their preparation and pharmaceutical utility, particularly including contraception and treatment of benign or malignant neoplastic diseases, having the general structure: 1 wherein R 1 and R 2 may be single substituents or fused to form spirocyclic rings.

  本发明涉及取代的吲哚啉衍生物化合物，它们是孕激素受体拮抗剂，包括其制备和药用，特别是包括避孕和治疗良性或恶性肿瘤疾病，具有以下一般结构：1，其中R1和R2可以是单个取代基或融合形成螺环。
• Cyclothiocarbamate derivatives as progesterone receptor modulators
  申请人：Zhang Puwen

  公开号：US20060142280A1

  公开（公告）日：2006-06-29

  Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and Q 1 are defined herein.

  本方法提供了使用具有孕激素受体激动剂作用的化合物进行避孕和单独或与雌激素受体激动剂或孕激素受体拮抗剂联合治疗孕激素相关疾病的方法。这些化合物具有以下结构： 其中，R1、R2、R3、R4、R5和Q1在此定义。
• CYCLOTHIOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS
  申请人：Zhang Puwen

  公开号：US20090281096A1

  公开（公告）日：2009-11-12

  Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and Q 1 are defined herein.

  本发明提供了使用化合物作为孕激素受体激动剂进行避孕和治疗孕激素相关疾病的方法，这些化合物可以单独使用或与雌激素受体激动剂或孕激素受体拮抗剂联合使用。这些化合物具有以下结构：其中R1，R2，R3，R4，R5和Q1如本文所定义。