9H-fluren-9-ylmethyl-6-[5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-1,3-benzoxazine-1(4H)-carboxylate | 304858-49-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9H-fluren-9-ylmethyl-6-[5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-1,3-benzoxazine-1(4H)-carboxylate
• 英文别名: 9H-fluoren-9-ylmethyl-6-[5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-3,1-benzoxazine-1(4H)-carboxylate；9H-fluoren-9-ylmethyl 6-(5-cyano-1H-pyrrol-2-yl)-2,4,4-trimethyl-2H-3,1-benzoxazine-1-carboxylate
• CAS: 304858-49-9
• 化学式: C₃₁H₂₇N₃O₃
• 分子量: 489.574
• InChiKey: AJOMTSLJGBPARH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9H-fluren-9-ylmethyl-6-[5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-1,3-benzoxazine-1(4H)-carboxylate 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 以56%的产率得到5-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)1H-pyrrole-2-carbonitrile
  参考文献：
  名称：

  Quinazolinone and benzoxazine derivatives as progesterone receptor modulators

  摘要：

  这项发明提供了具有以下一般结构的孕激素受体激动剂和拮抗剂的化合物：其中：R1和R2分别选择自H、CORA或NRBCORA，或者可选择取代的烷基、烯基、炔基、环烷基、芳基或杂环基；或者R1和R2融合形成：3到8成员的螺环烷基、烯基或杂环环；RA为H或可选择取代的烷基、芳基、烷氧基或氨基烷基；RB为H、C1至C3烷基或取代的C1至C3烷基；R3为H、OH、NH2、CORC或可选择取代的烷基、烯基或炔基；RC为H或可选择取代的烷基、芳基、烷氧基或氨基烷基；R4为H、卤素、CN、NO2或可选择取代的烷基、炔基、烷氧基、氨基或氨基烷基；R5为可选择取代的苯或含有1、2或3个来自O、S、SO、SO2或NR6的杂原子的五元或六元环；R6为H或C1至C3烷基；G1为O、NR7或CR7R8；G2为CO、CS或CR7R8；条件是当G1为O时，G2为CR7R8，且G1和G2不能同时为CR7R8；R7和R8为H或可选择取代的烷基、芳基或杂环基；或其药用盐，以及在哺乳动物中使用这些化合物作为孕激素受体激动剂或拮抗剂的方法。

  公开号：

  US06358948B1
• 作为产物：
  描述：

  9H-fluren-9-ylmethyl-6-[1-(tert-butoxycarbonyl)-5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-1,3-benzoxazine-1(4H)-carboxylate 以97%的产率得到9H-fluren-9-ylmethyl-6-[5-cyano-1H-pyrrol-2-yl]-2,4,4-trimethyl-2H-1,3-benzoxazine-1(4H)-carboxylate
  参考文献：
  名称：

  Quinazolinone and benzoxazine derivatives as progesterone receptor modulators

  摘要：

  这项发明提供了具有以下一般结构的孕激素受体激动剂和拮抗剂的化合物：其中：R1和R2分别选择自H、CORA或NRBCORA，或者可选择取代的烷基、烯基、炔基、环烷基、芳基或杂环基；或者R1和R2融合形成：3到8成员的螺环烷基、烯基或杂环环；RA为H或可选择取代的烷基、芳基、烷氧基或氨基烷基；RB为H、C1至C3烷基或取代的C1至C3烷基；R3为H、OH、NH2、CORC或可选择取代的烷基、烯基或炔基；RC为H或可选择取代的烷基、芳基、烷氧基或氨基烷基；R4为H、卤素、CN、NO2或可选择取代的烷基、炔基、烷氧基、氨基或氨基烷基；R5为可选择取代的苯或含有1、2或3个来自O、S、SO、SO2或NR6的杂原子的五元或六元环；R6为H或C1至C3烷基；G1为O、NR7或CR7R8；G2为CO、CS或CR7R8；条件是当G1为O时，G2为CR7R8，且G1和G2不能同时为CR7R8；R7和R8为H或可选择取代的烷基、芳基或杂环基；或其药用盐，以及在哺乳动物中使用这些化合物作为孕激素受体激动剂或拮抗剂的方法。

  公开号：

  US06358948B1

文献信息

• [EN] CONTRACEPTIVE COMPOSITIONS CONTAINING QUINAZOLINONE AND BENZOXAZINE DERIVATIVES<br/>[FR] COMPOSITIONS CONTRACEPTIVES CONTENANT DE LA QUINAZOLINONE ET DES DERIVES DE BENZOXAZINE
  申请人：AMERICAN HOME PROD

  公开号：WO2000066165A1

  公开（公告）日：2000-11-09

  This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of general structure: (I) wherein: R?1 and R2¿ are H, COR?A, or NRBCORA¿, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic; or R?1 and R2¿ fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RB is H or alkyl; R3 is H, OH, NH¿2, COR?C or alkyl, alkenyl, or alkynyl; RC is H, alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO¿2?, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R?5¿ is benzen or 5- or 6-membered heterocyclic ring; R6 is H or alkyl; G¿1? is O, NR7, or CR7R8; G2 is CO or CR7R8; provided that when G1 is O, G2 is CR7R8, and G1 and G2 cannot both be CR7R8; R7 and R8 are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof. These methods may be used for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.

  本发明涉及循环组合疗法，利用与孕激素、雌激素或两者结合使用的化合物，这些化合物是一般结构的孕激素受体拮抗剂：（I）其中：R?1和R2¿为H、COR?A或NRBCORA¿、烷基、烯基、炔基、环烷基、芳基或杂环基；或R?1和R2¿融合形成3至8个成员的螺环烷基、烯基或杂环环；RA为H或可选择的取代烷基、芳基、烷氧基或氨基烷基；RB为H或烷基；R3为H、OH、NH¿2、COR?C或烷基、烯基或炔基；RC为H、烷基、芳基、烷氧基或氨基烷基；R4为H、卤素、CN、NO¿2？、烷基、炔基、烷氧基、氨基或氨基烷基；R?5¿为苯或5-或6-成员杂环环；R6为H或烷基；G¿1？为O、NR7或CR7R8；G2为CO或CR7R8；但是当G1为O时，G2为CR7R8，且G1和G2不能同时为CR7R8；R7和R8为H或可选择的取代烷基、芳基或杂环基团；或其药学上可接受的盐。这些方法可用于避孕或治疗和/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、子宫内膜癌和腺癌、卵巢、乳腺、结肠、前列腺癌的最小化副作用或周期性月经出血。本发明的其他用途包括刺激食欲。
• Cyclic regimens using quinazolinone and benzoxazine derivatives
  申请人：Wyeth

  公开号：US06498154B1

  公开（公告）日：2002-12-24

  This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of the general structure: wherein: R1 and R2 are H, CORA, or NRBCORA, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic; or R1 and R2 fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RB is H or alkyl; R3 is H, OH, NH2, CORC or alkyl, alkenyl, or alkynyl; RC is H, alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO2, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R5 is benzene or 5- or 6-membered heterocyclic ring; R6 is H or alkyl; G1 is O, NR7, or CR7R8; G2 is CO or CR7R8; provided that when G1 is O, G2 is CR7R8, and G1 and G2 cannot both be CR7R8; R7 and R8 are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof. These methods may be used for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.

  本发明涉及循环联合疗法，利用孕激素受体拮抗剂与孕激素、雌激素或两者的结合物相结合，其一般结构为：其中：R1和R2为H、CORA或NRBCORA、烷基、烯基、炔基、环烷基、芳基或杂环基；或R1和R2融合形成3至8个成员的螺环烷基、烯基或杂环环；RA为H或可选取代的烷基、芳基、烷氧基或氨基烷基；RB为H或烷基；R3为H、OH、NH2、CORC或烷基、烯基或炔基；RC为H、烷基、芳基、烷氧基或氨基烷基；R4为H、卤素、CN、NO2、烷基、炔基、烷氧基、氨基或氨基烷基；R5为苯环或5-或6-成员杂环环；R6为H或烷基；G1为O、NR7或CR7R8；G2为CO或CR7R8；前提是当G1为O时，G2为CR7R8，且G1和G2不能同时为CR7R8；R7和R8为H或可选取代的烷基、芳基或杂环基；或其药学上可接受的盐。这些方法可用于避孕或治疗和/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、子宫内膜癌、卵巢癌、乳腺癌、结肠癌、前列腺癌或最小化副作用或周期性月经出血。本发明的其他用途包括促进食物摄入。
• 1,2,3,4-tetrahydro-2-thioxo-quinolinyl and 1,2,3,4-tetrahydro-2-oxo-quinolinyl derivatives as progesterone receptor modulators
  申请人：Wyeth

  公开号：US06693103B2

  公开（公告）日：2004-02-17

  This invention provides compounds which are agonists and antagonists of the progesterone receptor having the general structure: wherein: R1 and R2 are independently selected from H, CORA, or NRBCORA, or optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic moieties; or R1 and R2 are fused to form: 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RA is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl; R3 is H, OH, NH2, CORC or optionally substituted alkyl, alkenyl, or alkynyl; RC is H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; R4 is H, halogen, CN, NO2, or optionally substituted alkyl alkynyl, alkoxy, amino or aminoalkyl; R5 is an optionally substituted benzene or five or six membered ring with 1, 2, or 3 heteroatoms selected from O, S, SO, SO2 or NR6; R6 is H or C1 to C3 alkyl; G1 is O, NR7, or CR7R8; G2 is CO, CS, or CR7R8; provided that when G1 is O, G2 is CR7R8, and G1 and G2 cannot both be CR7R8; R7 and R8 are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof, and methods using these compounds in mammals as agonists or antagonists of the progesterone receptor.

  本发明提供了具有下列一般结构的孕激素受体激动剂和拮抗剂化合物：其中：R1和R2独立地选自H、CORA、或NRBCORA，或可选地取代烷基、烯基、炔基、环烷基、芳基或杂环基；或R1和R2融合形成：3到8元杂环螺环烷基、烯基或杂环环；RA为H或可选地取代的烷基、芳基、烷氧基或氨基烷基；RB为H、C1到C3烷基或取代的C1到C3烷基；R3为H、OH、NH2、CORC或可选地取代的烷基、烯基或炔基；RC为H或可选地取代的烷基、芳基、烷氧基或氨基烷基；R4为H、卤素、CN、NO2或可选地取代的烷基炔基、烷氧基、氨基或氨基烷基；R5为可选地取代的苯或带有1、2或3个杂原子（选自O、S、SO、SO2或NR6）的五元或六元环；R6为H或C1到C3烷基；G1为O、NR7或CR7R8；G2为CO、CS或CR7R8；前提是当G1为O时，G2为CR7R8，且G1和G2不能同时为CR7R8；R7和R8为H或可选地取代的烷基、芳基或杂环基；或其药学上可接受的盐，以及在哺乳动物中使用这些化合物作为孕激素受体激动剂或拮抗剂的方法。
• CONTRACEPTIVE COMPOSITIONS CONTAINING QUINAZOLINONE AND BENZOXAZINE DERIVATIVES
  申请人：American Home Products Corporation

  公开号：EP1173206A1

  公开（公告）日：2002-01-23
• US6358948B1
  申请人：——

  公开号：US6358948B1

  公开（公告）日：2002-03-19