2-dimethylamino-6-methoxy-3-[4-(2-(piperidin-1-yl)ethoxy)benzoyl]benzo[b]thiophene | 165742-76-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-dimethylamino-6-methoxy-3-[4-(2-(piperidin-1-yl)ethoxy)benzoyl]benzo[b]thiophene
• 英文别名: [2-dimethylamino-6-methoxybenzothien-3-yl] [4-[2-(1-piperidinyl)ethoxy]phenyl]-methanone；[2-dimethylamino-6-methoxybenzothien-3-yl] [4-[2-(l-piperidinyl)ethoxy]phenyl]methanone；[2-dimethylamino-6-methoxybenzothien-3-yl] [4-[2-(1-piperdinyl)ethoxy]phenyl]methanone；(2-dimethylamino-6-methoxy-benzo[b]thiophen-3-yl)-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone；[2-Dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone；[2-(dimethylamino)-6-methoxy-1-benzothiophen-3-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• CAS: 165742-76-7
• 化学式: C₂₅H₃₀N₂O₃S
• 分子量: 438.591
• InChiKey: TZAVGZOZSPFAEO-UHFFFAOYSA-N

物化性质

• 沸点：
  612.1±55.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-dimethylamino-6-methoxy-3-[4-(2-(piperidin-1-yl)ethoxy)benzoyl]benzo[b]thiophene 在 三氯化铝 、 乙硫醇 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 雷洛昔芬
  参考文献：
  名称：

  Synergistic methodologies for the synthesis of 3-aroyl-2-arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene

  摘要：

  Difunctionalized benzo[b] thiophene intermediates are prepared which allow fully independent elaboration of the 2-aryl position or the tether position of benzo[b]thiophene-based selective estrogen receptor modulators (SERMs). Two concise syntheses of the SERM raloxifene (Evista(R)) are presented. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00955-7
• 作为产物：
  描述：

  6-甲氧基-N,N-二甲基苯并[b]噻吩-2-胺 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 氯苯 为溶剂， 反应 0.25h， 生成 2-dimethylamino-6-methoxy-3-[4-(2-(piperidin-1-yl)ethoxy)benzoyl]benzo[b]thiophene
  参考文献：
  名称：

  Synergistic methodologies for the synthesis of 3-aroyl-2-arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene

  摘要：

  Difunctionalized benzo[b] thiophene intermediates are prepared which allow fully independent elaboration of the 2-aryl position or the tether position of benzo[b]thiophene-based selective estrogen receptor modulators (SERMs). Two concise syntheses of the SERM raloxifene (Evista(R)) are presented. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00955-7

文献信息

• Benzo [B] thiophene compounds, and compositions for treating bone loss,
  申请人：Eli Lilly and Company

  公开号：US05998442A1

  公开（公告）日：1999-12-07

  The invention provides benzo[b]thiophene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions including hyperlipidemia and related cardiovascular pathologies.

  这项发明提供了苯并[b]噻吩化合物、配方和抑制骨质流失或骨吸收的方法，特别是针对骨质疏松症和与心血管相关的病理条件，包括高脂血症和相关的心血管病理条件。
• Benzothiophene compounds
  申请人：Eli Lilly and Company

  公开号：US05728724A1

  公开（公告）日：1998-03-17

  The present invention relates to compounds of formula I ##STR1## wherein R.sup.1 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); R.sup.2 is 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl, benzothienyl, or --CH.sub.2 C.sub.6 H.sub.5 ; any of which may be optionally substituted with 1-3 substituents independently selected from the group halo, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); X is --CH.sub.2 --, --CO--, or --CH(OH)--; n is 2 or 3; and R.sup.3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof. The present invention further relates to pharmaceutical compositions containing compounds of formula I, and the use of such compounds, for alleviating the symptoms of post-menopausal syndrome, particularly osteoporosis, cardiovascular related pathological conditions, and estrogen-dependent cancer. The compounds of the present invention also are useful for inhibiting uterine fibroid disease and endometriosis in women and aortal smooth muscle cell proliferation, particularly restenosis, in humans.

  本发明涉及式I的化合物，其中R.sup.1是--H，--OH，--O（C.sub.1-C.sub.4烷基），--OCOC.sub.6H.sub.5，--OCO（C.sub.1-C.sub.6烷基）或--OSO.sub.2（C.sub.4-C.sub.6烷基）; R.sup.2是1-萘基，2-萘基，2-噻吩基，3-噻吩基，苯并噻吩基或--CH.sub.2C.sub.6H.sub.5；其中任何一个可以选择性地被1-3个取代基独立地选自卤素，--OH，--O（C.sub.1-C.sub.4烷基），--OCOC.sub.6H.sub.5，--OCO（C.sub.1-C.sub.6烷基）或--OSO.sub.2（C.sub.4-C.sub.6烷基）; X是--CH.sub.2--，--CO--或--CH（OH）--; n为2或3; R.sup.3是1-哌啶基，1-吡咯烷基，甲基-1-吡咯烷基，二甲基-1-吡咯烷基，4-吗啉基，二甲胺，二乙胺或1-己亚胺；或其药学上可接受的盐。本发明还涉及含有式I化合物的制药组合物，以及使用这种化合物缓解绝经后综合症状，特别是骨质疏松症，心血管相关病理状况和雌激素依赖性癌症的症状。本发明的化合物还可用于抑制女性子宫肌瘤和子宫内膜异位症以及抑制主动脉平滑肌细胞增殖，特别是再狭窄。
• [EN] DIHYDRO-DIBENZO[B,E]OXEPINE BASED SELECTIVE ESTROGEN RECEPTOR MODULATORS, COMPOSITIONS AND METHODS<br/>[FR] MODULATEURS SELECTIFS DU RECEPTEUR DES OESTROGENES UTILISANT UNE DIHYDRO-DIBENZO[B,E]OXEPINE, COMPOSITIONS ET PROCEDES ASSOCIES
  申请人：LILLY CO ELI

  公开号：WO2004009603A1

  公开（公告）日：2004-01-29

  The present invention provides a compound of the formula (I) wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C2-C6 alkyl); R0, R2 and R3 are each independently -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), -OSO2(C2-C6 alkyl) or halo; R4 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; X is -S- or -HC=CH-; G is -O-, -S-, -SO-, SO2, or -N(R5)-, wherein R5 is -H or C1-C4 alkyl; and Y is -O-, -S-, -NH-, -NMe-, or -CH2-; or a pharmaceutically acceptable salt thereof; pharmaceutical compositions thereof, optionally in combination with estrogen and progestin; methods of inhibiting a disease associated with estrogen deprivation; and methods for inhibiting a disease associated with an aberrant physiological response to endogenous estrogen.

  本发明提供了一种式（I）的化合物，其中R1是-H，-OH，-O（C1-C4烷基），-OCOC6H5，-OCO（C1-C6烷基）或-OSO2（C2-C6烷基）; R0，R2和R3各自独立地是-H，-OH，-O（C1-C4烷基），-OCOC6H5，-OCO（C1-C6烷基），-OSO2（C2-C6烷基）或卤素; R4是1-哌啶基，1-吡咯烷基，甲基-1-吡咯烷基，二甲基-1-吡咯烷基，4-吗啉基，二甲胺基，二乙胺基，二异丙基胺基或1-己亚甲基亚胺基; n为2或3; X为-S-或-HC=CH-; G为-O-，-S-，-SO-，SO2或-N（R5）-，其中R5为-H或C1-C4烷基; Y为-O-，-S-，-NH-，-NMe-或-CH2-; 或其药学上可接受的盐; 其药物组合物，可选地与雌激素和孕激素结合; 抑制与雌激素缺乏相关的疾病的方法; 以及抑制与内源性雌激素异常生理反应相关的疾病的方法。
• [EN] DERIVATIVE OF DIHYDRO-DIBENZO (A) ANTHRACENES AND THEIR USE AS SELECTIVE ESTROGEN RECEPTOR MODULATORS<br/>[FR] DERIVE DE DIHYDRO-DIBENZO (A) ANTHRACENES, ET SON UTILISATION COMME OESTROGENE SUR MESURE (SERM)
  申请人：LILLY CO ELI

  公开号：WO2004029047A1

  公开（公告）日：2004-04-08

  The present invention provides a compound of the formula (I) wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C2-C6 alkyl); R0, R2 and R3 are each independently -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), -OSO2(C2-C6 alkyl) or halo; R4 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; X is S- or -HC=CH-; and Y is O-, -S-, -NH-, -NMe-, or -CH2-;or a pharmaceutically acceptable salt thereof; pharmaceutical compositions thereof, optionally in combination with estrogen and progestin; methods of inhibiting a disease associated with estrogen deprivation; and methods for inhibiting a disease associated with an aberrant physiological response to endogenous estrogen.

  本发明提供一种化合物，其化学式为（I），其中R1为-H，-OH，-O（C1-C4烷基），-OCOC6H5，-OCO（C1-C6烷基）或-OSO2（C2-C6烷基）；R0、R2和R3各自独立地为-H，-OH，-O（C1-C4烷基），-OCOC6H5，-OCO（C1-C6烷基），-OSO2（C2-C6烷基）或卤素；R4为1-哌啶基，1-吡咯烷基，甲基-1-吡咯烷基，二甲基-1-吡咯烷基，4-吗啉基，二甲氨基，二乙氨基，二异丙基氨基或1-己亚甲基亚胺基；n为2或3；X为S-或-HC=CH-；Y为O-，-S-，-NH-，-NMe-或-CH2-；或其药学上可接受的盐；以及与雌激素和孕激素组合的药物组合物；用于抑制与雌激素剥夺相关的疾病的方法；以及用于抑制与内源性雌激素异常生理反应相关的疾病的方法。
• Benzothiphene derivatives for treating resistant tumors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0773217A1

  公开（公告）日：1997-05-14

  This invention provides a series of substituted benzo[b]thiophenes useful in reversing multidrug resistance in a resistant neoplasm. The present invention also provides methods for reversing the multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted benzothiophene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted benzothiophene in combination with an oncolytic agent.

  这项发明提供了一系列取代苯并[b]噻吩，可用于逆转耐药肿瘤的多药耐药性。本发明还提供了通过给需要该治疗的哺乳动物使用取代苯并噻吩来逆转多药耐药性的方法。该发明还提供了一种治疗哺乳动物肿瘤的方法，包括给需要此治疗的哺乳动物同时使用取代苯并噻吩和肿瘤溶解剂。