(6-hydroxy-2-cyclohexylbenzo[b]thien-3-yl)-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone | 150797-71-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-hydroxy-2-cyclohexylbenzo[b]thien-3-yl)-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
• 英文别名: (2-Cyclohexyl-6-hydroxy-benzo[b]thiophen-3-yl)-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone；Methanone, (2-cyclohexyl-6-hydroxybenzo(b)thien-3-yl)(4-(2-(1-piperidinyl)ethoxy)phenyl)-；(2-cyclohexyl-6-hydroxy-1-benzothiophen-3-yl)-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• CAS: 150797-71-0
• 化学式: C₂₈H₃₃NO₃S
• 分子量: 463.641
• InChiKey: IZGMIMKTZXSTLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6-hydroxy-2-cyclohexylbenzo[b]thien-3-yl)-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone 在 三乙基硅烷 、 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-Cyclohexyl-3-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-benzo[b]thiophen-6-ol
  参考文献：
  名称：

  Synthesis and pharmacology of 2-alkyl raloxifene analogs

  摘要：

  A series of 2-alkyl and 2-cycloalkyl raloxifene analogs have been prepared and evaluated in both in vitro and in vivo models of estrogen/antiestrogen activity. In particular, the 2-cyclohexyl analogs show promise as potent selective estrogen-receptor modulators (SERMs).

  DOI：

  10.1016/0960-894x(95)00575-e
• 作为产物：
  描述：

  2-dimethylamino-6-methoxy-3-[4-(2-(piperidin-1-yl)ethoxy)benzoyl]benzo[b]thiophene 在 三氯化铝 、 丙烷-1-硫醇 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 6.5h， 生成 (6-hydroxy-2-cyclohexylbenzo[b]thien-3-yl)-[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
  参考文献：
  名称：

  Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene

  摘要：

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

  DOI：

  10.1021/jm9606352

文献信息

• Benzothiophene derivative
  申请人：Teikoku Hormone Mfg. Co., Ltd.

  公开号：US05472962A1

  公开（公告）日：1995-12-05

  A benzothiophene derivative represented by the formula ##STR1## or a salt thereof has an excellent antiestrogenic activity, and is useful as a therapeutic agent of breast cancer, endometrial cancer, endometriosis, mastopathy, etc. This compound is characterized in that the 2-position (the substituent R.sup.2) of the benzothiophene nucleus is substituted by a halogen atom; a lower alkyl group; or a cycloalkyl or cycloalkenyl group optionally substituted by a lower alkyl group, a hydroxyl group, acyloxy group or an oxo group.

  一种由公式##STR1##表示的苯并噻吩衍生物或其盐具有出色的抗雌激素活性，并可用作乳腺癌、子宫内膜癌、子宫内膜异位症、乳房病等的治疗剂。该化合物的特点在于苯并噻吩核的2位（取代基R.sup.2）被卤素原子；低碳基；或环烷基或环烯基取代，可选地取代为低碳基，羟基，酰氧基或羰基。
• Methods for inhibiting bone loss using substituted benzothiophene
  申请人：Eli Lilly and Company

  公开号：US05441964A1

  公开（公告）日：1995-08-15

  A method of inhibiting bone loss comprising administering to a human in need of treatment an effective amount of a substituted benzothiophene.

  一种抑制骨质流失的方法，包括向需要治疗的人类施用有效量的取代苯并噻吩。
• Methods for lowering serum cholesterol
  申请人：Eli Lilly and Company

  公开号：US05482950A1

  公开（公告）日：1996-01-09

  A method of lowering serum cholesterol levels comprising administering to a human in need of treatment an effective amount of a compound having the formula ##STR1## wherein R is hydrogen; hydroxy; C.sub.1 -C.sub.6 alkoxy; a group of the formula --O--C(O)--R.sup.a, wherein R.sup.a is hydrogen, optionally substituted C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl optionally substituted with aryl, C.sub.3 -C.sub.7 cycloalkyl, optionally substituted aryl or R.sup.a is optionally substituted --O--aryl, or R is a group of the formula --O--SO.sub.2 --R.sup.b wherein R.sup.b may be C.sub.1 -C.sub.6 alkyl or optionally substituted aryl; or R is carbamoyloxy wherein the nitrogen may be substituted once or twice with C.sub.1 -C.sub.6 alkyl; or R is a group of the formula --O--C(O)R.sup.c --O--(C.sub.1 -C.sub.6 alkyl) wherein R.sup.c is a bond or C.sub.1 -C.sub.6 alkanediyl; R.sup.1 is halo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.7 alkyl substituted with C.sub.1 -C.sub.6 alkyl, substituted or unsubstituted C.sub.3 -C.sub.7 cycloalkyl, or substituted or unsubstituted C.sub.3 -C.sub.7 cycloalkenyl; R.sup.2 is O or CH.sub.2 ; R.sup.3 is CH.sub.2 or (CH.sub.2).sub.2 ; R.sup.4 is ##STR2## CH.sub.2, or a bond; and R.sup.5 is pyrrolidinyl or piperidinyl.

  一种降低血清胆固醇水平的方法，包括向需要治疗的人类施用具有以下式子的化合物的有效量：##STR1## 其中R是氢；羟基；C.sub.1-C.sub.6烷氧基；式子--O--C(O)--R.sup.a的基团，其中R.sup.a是氢，可选择地取代的C.sub.1-C.sub.6烷基，C.sub.1-C.sub.6烯基，可选择地用芳基取代，C.sub.3-C.sub.7环烷基，可选择地用芳基取代，或R.sup.a是可选择地取代的--O--芳基，或R是式子--O--SO.sub.2--R.sup.b的基团，其中R.sup.b可以是C.sub.1-C.sub.6烷基或可选择地取代的芳基；或R是羰酰氧基，其中氮可以一次或两次用C.sub.1-C.sub.6烷基取代；或R是式子--O--C(O)R.sup.c--O--(C.sub.1-C.sub.6烷基)的基团，其中R.sup.c是键或C.sub.1-C.sub.6烷二基；R.sup.1是卤素，C.sub.1-C.sub.6烷基，C.sub.1-C.sub.7烷基，用C.sub.1-C.sub.6烷基取代或未取代的C.sub.3-C.sub.7环烷基，或用C.sub.3-C.sub.7环烯基取代或未取代的C.sub.3-C.sub.7环烷基；R.sup.2是O或CH.sub.2；R.sup.3是CH.sub.2或(CH.sub.2).sub.2；R.sup.4是##STR2## CH.sub.2或键；R.sup.5是吡咯烷基或哌啶基。
• Methods for inhibiting uterine fibrosis
  申请人：ELI LILLY AND COMPANY

  公开号：EP0650724A1

  公开（公告）日：1995-05-03

  A method of inhibiting uterine fibrosis comprising administering to a human in need of treatment an effective amount of a compound having the formula    wherein R is hydrogen; hydroxy; C₁-C₆ alkoxy; a group of the formula -O-C(O)-Ra, wherein Ra is hydrogen, C₁-C₆ alkyl optionally substituted with amino, halo, carbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₇ alkanoyloxy, carbamoyl and/or aryl; or Ra is C₁-C₆ alkenyl optionally substituted with aryl; or Ra is a C₃-C₇ cycloalkyl; or Ra is aryl optionally substituted with hydroxy, C₁-C₆ alkyl, C₁-C₆ alkoxy, and/or halo; or Ra is -O-aryl, said aryl optionally substituted with hydroxy C₁-C₆ alkyl, C₁-C₆ alkoxy, and/or halo,    or R is a group of the formula -O-SO₂-Rb wherein Rb may be C₁-C₆ alkyl or aryl optionally substituted with C₁-C₆ alkyl;    or R is carbamoyloxy wherein the nitrogen may be substituted once or twice with C₁-C₆ alkyl;    or R is a group of the formula -O-C(O)Rc-O-(C₁-C₆ alkyl) wherein Rc is a bond or C₁-C₆ alkanediyl;    R¹ is halo, C₁-C₆ alkyl, C₁-C₇ alkyl substituted with C₁-C₆ alkyl, substituted or unsubstituted C₃-C₇ cycloalkyl, or substituted or unsubstituted C₃-C₇ cycloalkenyl;    R² is O or CH₂;    R³ is CH₂ or (CH₂)₂;    R⁴ is CH₂, or a bond; and    R⁵ is amino, nitrilo optionally substituted once or twice with C₁-C₆ alkyl; or an N-heterocyclic ring which optionally has another hetero atom selected from N, O, or S in said ring; or a pharmaceutically acceptable salt or solvate thereof.

  抑制子宫纤维化的方法包括向需要治疗的人类施用具有以下式子的化合物的有效量： 其中，R为氢、羟基、C₁-C₆烷氧基、式子-O-C（O）-Ra的基团，其中Ra为氢、C₁-C₆烷基，该烷基可选地带有氨基、卤素、羰基、C₁-C₆烷氧羰基、C₁-C₇烷酰氧基、氨基甲酰基和/或芳基；或Ra为可选地带有芳基的C₁-C₆烯基；或Ra为C₃-C₇环烷基；或Ra为可选地带有羟基、C₁-C₆烷基、C₁-C₆烷氧基和/或卤素的芳基；或Ra为-O-芳基，该芳基可选地带有羟基、C₁-C₆烷基、C₁-C₆烷氧基和/或卤素，或R为式子-O-SO₂-Rb的基团，其中Rb可以是C₁-C₆烷基或可选地带有C₁-C₆烷基的芳基；或R为氨基甲酰氧基，其中氮原子可以被C₁-C₆烷基取代一次或两次；或R为式子-O-C（O）Rc-O-（C₁-C₆烷基）的基团，其中Rc为键或C₁-C₆烷二基；R¹为卤素、C₁-C₆烷基、可带有C₁-C₆烷基的C₁-C₇烷基、取代或未取代的C₃-C₇环烷基，或取代或未取代的C₃-C₇环烯基；R²为O或CH₂；R³为CH₂或（CH₂）₂；R⁴为CH₂或键；R⁵为氨基、一次或两次可选地取代C₁-C₆烷基的硝基基或在该环中可选地具有另一种来自N、O或S的杂原子的N-杂环环；或其药学上可接受的盐或溶剂化物。
• Methods for inhibiting bone loss
  申请人：ELI LILLY AND COMPANY

  公开号：EP0651998A1

  公开（公告）日：1995-05-10

  A method of inhibiting bone loss comprising administering to a human in need of treatment an effective amount of a compound having the formula    wherein R is hydrogen; hydroxy; C₁-C₆ alkoxy; a group of the formula -O-C(O)-Ra, wherein Ra is hydrogen, C₁-C₆ alkyl optionally substituted with amino, halo, carbonyl, C₁-C₆ alkoxycarbonyl, C₁-C₇ alkanoyloxy, carbamoyl and/or aryl; or Ra is C₁-C₆ alkenyl optionally substituted with aryl; or Ra is a C₃-C₇ cycloalkyl; or Ra is aryl optionally substituted with hydroxy, C₁-C₆ alkyl, C₁-C₆ alkoxy, and/or halo; or Ra is -O-aryl, said aryl optionally substituted with hydroxy C₁-C₆ alkyl, C₁-C₆ alkoxy, and/or halo,    or R is a group of the formula -O-SO₂-Rb wherein Rb may be C₁-C₆ alkyl or aryl optionally substituted with C₁-C₆ alkyl;    or R is carbamoyloxy wherein the nitrogen may be substituted once or twice with C₁-C₆ alkyl;    or R is a group of the formula -O-C(O)Rc-O-(C₁-C₆ alkyl) wherein Rc is a bond or C₁-C₆ alkanediyl;    R¹ is halo, C₁-C₆ alkyl, C₁-C₇ alkyl substituted with C₁-C₆ alkyl, substituted or unsubstituted C₃-C₇ cycloalkyl, or substituted or unsubstituted C₃-C₇ cycloalkenyl;    R² is O or CH₂;    R³ is CH₂ or (CH₂)₂;    R⁴ is CH₂, or a bond; and    R⁵ is amino, nitrilo optionally substituted once or twice with C₁-C₆ alkyl; or an N-heterocyclic ring which optionally has another hetero atom selected from N, O, or S in said ring; or a pharmaceutically acceptable salt or solvate thereof.

  一种抑制骨质流失的方法，包括向需要治疗的人体内投与一定量的具有以下式子的化合物：其中R为氢；羟基；C₁-C₆烷氧基；式子-O-C(O)-Ra的基团，其中Ra为氢，C₁-C₆烷基，可选地被氨基，卤素，羰基，C₁-C₆烷氧羰基，C₁-C₇脂肪酰氧基，氨基甲酰和/或芳基取代；或Ra为C₁-C₆烯基，可选地被芳基取代；或Ra为C₃-C₇环烷基；或Ra为芳基，可选地被羟基，C₁-C₆烷基，C₁-C₆烷氧基和/或卤素取代；或Ra为-O-芳基，所述芳基可选地被羟基，C₁-C₆烷基，C₁-C₆烷氧基和/或卤素取代，或R为式子-O-SO₂-Rb的基团，其中Rb可以是C₁-C₆烷基或可选地被C₁-C₆烷基取代的芳基；或R为氨基甲酰氧基，其中氮原子可以被C₁-C₆烷基取代一次或两次；或R为式子-O-C(O)Rc-O-(C₁-C₆烷基)的基团，其中Rc为键或C₁-C₆烷二基；R¹为卤素，C₁-C₆烷基，可选地被C₁-C₆烷基取代的C₁-C₇烷基，取代或未取代的C₃-C₇环烷基，或取代或未取代的C₃-C₇环烯基；R²为O或CH₂；R³为CH₂或(CH₂)₂；R⁴为CH₂或键；R⁵为氨基，一次或两次可选地被C₁-C₆烷基取代的氮甲基，或在所述环中可选地有另一种异原子N、O或S的N-杂环，或其药学上可接受的盐或溶剂。