(1R,2R)-2,3-dihydro-1-(pyrrolidin-1-yl)-1H-inden-2-ol | 1158818-77-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (1R,2R)-2,3-dihydro-1-(pyrrolidin-1-yl)-1H-inden-2-ol
• 英文别名: (1R,2R)-1-pyrrolidin-1-ylindan-2-ol；trans-2,3-dihydro-2-hydroxy-(pyrrolidin-1-yl)-1H-indene；(1R,2R)-1-pyrrolidin-1-yl-2,3-dihydro-1H-inden-2-ol
• CAS: 1158818-77-9
• 化学式: C₁₃H₁₇NO
• 分子量: 203.284
• InChiKey: YWJGJYXDQXXXLJ-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2,3-dihydro-1-(pyrrolidin-1-yl)-1H-inden-2-ol 生成 trans-2,3-dihydro-1-methylamino-2-(pyrrolidin-1-yl)-1H-indene
  参考文献：
  名称：

  PENNEV, PENIO;RAJAGOPALANI, PARTHANARATHI;SCRIBAER, M.

  摘要：

  DOI：
• 作为产物：
  描述：

  茚 在 Jacobsen's catalyst 、 4-(3-苯基丙基)吡啶1-氧化物 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (1R,2R)-2,3-dihydro-1-(pyrrolidin-1-yl)-1H-inden-2-ol
  参考文献：
  名称：

  发现和优化1-苯氧基-2-氨基茚满作为Na + / H + 3型交换子（NHE3）的有效，选择性和口服生物利用抑制剂

  摘要：

  基于高通量筛选（HTS）的命中，描述了作为3 + Na + / H +交换剂（NHE3）抑制剂的1-苯氧基-2-氨基茚满的设计，合成及其构效关系。化学最优化导致发现了以13d为最佳化合物的有效，选择性和口服生物利用的NHE3抑制剂，显示出较高的体外通透性和缺乏CYP2D6抑制作用作为主要优化参数。将1-苯氧基-2-氨基茚满对准13d的X射线结构然后为NHE3抑制捕获指南提供了3D-QSAR模型以进行优化。这些模型显示出良好的相关系数，并可以进行活性估算。在计算机中针对Caco-2渗透性和CYP2D6抑制作用的ADMET模型也已成功应用于该系列。此外，对接CYP2D6 X射线结构为3D-QSAR模型提供了可靠的对齐方式。最终，重命名为SAR197的13d在体外和体内药代动力学（PK）和药理研究中进行了表征，以揭示其减少阻塞性睡眠呼吸暂停的潜力。

  DOI：

  10.1021/acs.jmedchem.6b00624

文献信息

• [EN] COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS<br/>[FR] COMPOSÉS ET PROCÉDÉS D'INHIBITION D'UN ANTIPORT À MÉDIATION PAR NHE DANS LE TRAITEMENT DE TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DE TROUBLES DU TRACTUS GASTRO-INTESTINAL
  申请人：ARDELYX INC

  公开号：WO2014029983A1

  公开（公告）日：2014-02-27

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物和治疗液体潴留或盐过多相关疾病的方法，例如心力衰竭（特别是充血性心力衰竭）、慢性肾脏疾病、晚期肾脏疾病、肝脏疾病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂诱导的液体潴留。本公开还涉及化合物和治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，包括治疗或减轻与胃肠道疾病相关的疼痛。
• Benzo-fused cycloalkane and oxa- and thia-, cycloalkane
  申请人：E. I. Du Pont De Nemours and Company

  公开号：US04929627A1

  公开（公告）日：1990-05-29

  Benzo-fused cycloalkane and oxa- and thia-cycloalkane trans-1,2-diamine compounds of the formula: ##STR1## wherein A, B, C, D, n, X, Y, R, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification, e.g., trans-3,4-dichloro-N-methyl-N-[2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetra hydronaphth-1-yl]benezeneacetamide, and the pharmaceutically acceptable salts or N-oxides thereof, are useful as analgesics and/or diuretics.

  苯并环烷和氧杂环烷、硫杂环烷的反-1,2-二胺化合物的化学式如下：##STR1## 其中A、B、C、D、n、X、Y、R、R.sup.1、R.sup.2和R.sup.3的定义如说明书中所述，例如trans-3,4-二氯-N-甲基-N-[2-(吡咯烷-1-基)-5-甲氧基-1,2,3,4-四氢萘-1-基]苯乙酰胺，以及其药学上可接受的盐或N-氧化物，可用作镇痛剂和/或利尿剂。
• N-(aminoindanyl)amides as analgesics and antiarrhythmics
  申请人：Roussel Uclaf

  公开号：US04988727A1

  公开（公告）日：1991-01-29

  A compound selected from the group consisting of all enantiomeric and diastereoisomeric forms possible of compounds of the formula ##STR1## wherein X is selected from the group consisting of hydrogen, halogen, and alkyl and alkoxy of 1 to 5 carbon atoms, R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, one of A and B being ##STR2## and the other being ##STR3## R is hydrogen or alkyl of 1 to 5 carbon atoms, Z is --(CH.sub.2).sub.n -- or branched alkylene of 2 to 8 carbon atoms, n is an integer from 0 to 5, Y is selected from the group consisting of naphthyl, indenyl, heterobicyclics and heteromonocyclic containing 5 to 6 ring members, all optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 5 carbon atoms, halogen, --OH, --CF.sub.3, --NO.sub.2, --NH.sub.2 monoalkylamino and dialkylamino of 1 to 4 alkyl carbon atoms and phenyl optionally substituted with at least one member of the group consisting of halogen and alkyl and alkoxy of 1 to 4 carbon atoms, R.sub.3 and R.sub.4 are individually hydrogen or alkyl or 1 to 5 carbon atoms or taken together with the nitrogen form a heterocyclic of 5 to 6 ring members and optionally containing --O--, --S-- or nitrogen in the ring and their non-toxic, pharmaceutically acceptable acid addition salts having central analgesic and antiarythmic activity among other activities.

  从公式 ##STR1## 的化合物中选择一个化合物，该化合物的所有对映异构体和顺反异构体形式均可，其中 X 从氢，卤素和1至5个碳原子的烷基和烷氧基的群中选择，R.sub.1和R.sub.2分别从氢和1至5个碳原子的烷基的群中选择，A和B中的一个为 ##STR2## 另一个为 ##STR3## R为氢或1至5个碳原子的烷基，Z为--(CH.sub.2).sub.n--或2至8个碳原子的支链烷基，n为0至5的整数，Y从萘基，茚基，含有5至6个环成员的杂环并环和杂单环中选择，所有这些环均可以选择至少一个烷基和1至5个碳原子的烷氧基，卤素，--OH，--CF.sub.3，--NO.sub.2，--NH.sub.2，1至4个烷基碳原子的单烷基和二烷基基氨基和苯，其中苯可以选择至少一个卤素和1至4个碳原子的烷基和烷氧基中的一个或多个成员进行替换，R.sub.3和R.sub.4分别为氢或1至5个碳原子的烷基，或者与氮一起形成5至6个环成员的杂环，其中该环可以选择在环中含有--O--，--S--或氮，并且它们的非毒性，药学上可接受的酸盐具有中枢镇痛和抗心律失常等活性。
• Benzo-fused cycloalkane and oxa- and thia-cycloalkane trans-1,2-diamine
  申请人：E. I. du Pont de Nemours and Company

  公开号：US05010085A1

  公开（公告）日：1991-04-23

  Benzo-fused cycloalkane and oxa- and thia-cycloalkane trans-1,2-diamine compounds of the formula: ##STR1## wherein A, B, C, D, n, X, Y, R, R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification, e.g., trans-3,4-dichloro-N-methyl-[2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahy dronaphth-1-yl]benzeneacetamide, and the pharmaceutically acceptable salts or N-oxides thereof, are useful as analgesics and/or diuretics.

  苯并环烷和氧杂环烷、硫杂环烷的trans-1,2-二胺化合物的化学式为：##STR1## 其中A、B、C、D、n、X、Y、R、R.sup.1、R.sup.2和R.sup.3如说明书中所定义，例如trans-3,4-二氯-N-甲基-[2-(吡咯烷-1-基)-5-甲氧基-1,2,3,4-四氢萘-1-基]苯乙酰胺以及其药学上可接受的盐或N-氧化物，可用作镇痛剂和/或利尿剂。
• Indanes and their use as antiarrhythmic agents
  申请人：Roussel Uclaf

  公开号：US04888355A1

  公开（公告）日：1989-12-19

  A compound selected from the group consisting of all enantiomeric and diastereoisomeric forms possible of compounds of the formula ##STR1## wherein X is selected from the group consisting of hydrogen, halogen, and alkyl and alkoxy of 1 to 5 carbon atoms, R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms, one of A and B being ##STR2## and the other being ##STR3## R is hydrogen or alkyl of 1 to 5 carbon atoms, Z is --(CH.sub.2).sub.n -- or branched alkylene of 2 to 8 carbon atoms, n is an integer from 0 to 5, Y is selected from the group consisting of naphthyl, indenyl, heterobicyclics and heteromonocyclic containing 5 to 6 ring members, all optionally substituted with at least one member of the group consisting of alkyl and alkoxy of 1 to 5 carbon atoms, halogen, --OH, --CF.sub.3, --NO.sub.2, --NH.sub.2, monoalkylamino and dialkylamino of 1 to 4 alkyl carbon atoms and phenyl optionally substituted with at least one member of the group consisting of halogen and alkyl and alkoxy of 1 to 4 carbon atoms, R.sub.3 and R.sub.4 are individually hydrogen or alkyl of 1 to 5 carbon atoms or taken together with the nitrogen form a heterocyclic of 5 to 6 ring members and optionally containing --O--, --S-- or nitrogen in the ring and their non-toxic, pharmaceutically acceptable acid addition salts having central analgesic and antiarythmic activity among other activities.

  从化合物公式中选择的一种化合物，该化合物公式包括所有可能的对映异构体和顺反异构体，其中X选自氢，卤素和1至5个碳原子的烷基和烷氧基的组，R.sub.1和R.sub.2分别选自氢和1至5个碳原子的烷基的组，A和B中的一个是##STR2##另一个是##STR3##，R是氢或1至5个碳原子的烷基，Z是--（CH.sub.2）.sub.n--或2至8个碳原子的支链烷基，n是0至5的整数，Y选自萘基，茚基，含有5至6个环成员的杂环双环和杂环单环，所有这些都可以选择性地用1至5个碳原子的烷基和烷氧基，卤素，-OH，-CF.sub.3，-NO.sub.2，-NH.sub.2，1至4个烷基碳原子的单烷基氨基和二烷基氨基以及苯基替代，其中至少一个成员选自卤素和1至4个碳原子的烷基和烷氧基的组，R.sub.3和R.sub.4分别是氢或1至5个碳原子的烷基，或与氮一起形成5至6个环成员的杂环，该杂环可以选择性地含有--O--，--S--或环中的氮，以及它们的非毒性，药学上可接受的酸加合物盐，具有中枢镇痛和抗心律失常等活性。