4-(10,11-dihydrodibenzo[b,f]azepin-5-yl)butan-1-ol | 88645-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 4-(10,11-dihydrodibenzo[b,f]azepin-5-yl)butan-1-ol
• 英文别名: 4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-butanol；5-(4-Hydroxybutyl)iminobibenzyl；4-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)butan-1-ol
• CAS: 88645-03-8
• 化学式: C₁₈H₂₁NO
• 分子量: 267.371
• InChiKey: MSNZFQMSFABRKM-UHFFFAOYSA-N

物化性质

• 沸点：
  215 °C(Press: 0.4 Torr)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  4-(10,11-dihydrodibenzo[b,f]azepin-5-yl)butan-1-ol 在 氯化亚砜 、 sodium carbonate 作用下， 以 四氢呋喃 、 苯 为溶剂， 生成 5-<4-Diethylamino-butyl>-iminodibenzyl
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Chemosensitizers in Multi-Drug-Resistant Plasmodium falciparum

  摘要：

  A series of new chemosensitizers (modulators) against chloroquine-resistant Plasmodium falciparum were designed and synthesized in an attempt to fabricate modulators with enhancing drug-resistant reversing efficacy and minimal side effects. Four aromatic amine ring systems-phenothiazine, iminodibenzyl, iminostilbene, and diphenylamine-were examined. Various tertiary amino groups including either noncyclic or cyclic aliphatic amines were introduced to explore the steric tolerance at the end of the side chain. The new compounds showed better drug-resistant reversing activity in chloroquine-resistant than in mefloquine-resistant cell lines and were generally more effective against chloroquine-resistant P. falciparum isolates from Southeast Asian (W2 and TM91C235) than those from South America (PC49 and RCS). Structure-activity relationship studies revealed that elongation of the alkyl side chain of the molecule retained the chemosensitizing activity, and analogues with four-carbon side chains showed superior activity. Furthermore, new modulators with phenothiazine ring exhibited the best chemosensitizing activity among the four different ring systems examined. Terminal amino function has limited steric tolerance as evidenced by the dramatic lose of the modulating activity, when the size of substituent at the amino group increases. The best new modulator synthesized in this study possesses all three optimized structural features, which consist of a phenothiazine ring and a pyrrolidinyl group joined by a four-carbon alkyl bridge. The fractional inhibitory concentration TIC) index of the best compound is 0.21, which is superior to that of verapamil (0.51), one of the best-known multi-drug-resistant reversing agents. Some of the analogues displayed moderate intrinsic in vitro antimalarial activity against a W-2 clone of P. falciparum.

  DOI：

  10.1021/jm010549o
• 作为产物：
  描述：

  N-[4-[(tetrahydropyran-2-yl)oxy]butyl]iminodibenzyl 在 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以73%的产率得到4-(10,11-dihydrodibenzo[b,f]azepin-5-yl)butan-1-ol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Chemosensitizers in Multi-Drug-Resistant Plasmodium falciparum

  摘要：

  A series of new chemosensitizers (modulators) against chloroquine-resistant Plasmodium falciparum were designed and synthesized in an attempt to fabricate modulators with enhancing drug-resistant reversing efficacy and minimal side effects. Four aromatic amine ring systems-phenothiazine, iminodibenzyl, iminostilbene, and diphenylamine-were examined. Various tertiary amino groups including either noncyclic or cyclic aliphatic amines were introduced to explore the steric tolerance at the end of the side chain. The new compounds showed better drug-resistant reversing activity in chloroquine-resistant than in mefloquine-resistant cell lines and were generally more effective against chloroquine-resistant P. falciparum isolates from Southeast Asian (W2 and TM91C235) than those from South America (PC49 and RCS). Structure-activity relationship studies revealed that elongation of the alkyl side chain of the molecule retained the chemosensitizing activity, and analogues with four-carbon side chains showed superior activity. Furthermore, new modulators with phenothiazine ring exhibited the best chemosensitizing activity among the four different ring systems examined. Terminal amino function has limited steric tolerance as evidenced by the dramatic lose of the modulating activity, when the size of substituent at the amino group increases. The best new modulator synthesized in this study possesses all three optimized structural features, which consist of a phenothiazine ring and a pyrrolidinyl group joined by a four-carbon alkyl bridge. The fractional inhibitory concentration TIC) index of the best compound is 0.21, which is superior to that of verapamil (0.51), one of the best-known multi-drug-resistant reversing agents. Some of the analogues displayed moderate intrinsic in vitro antimalarial activity against a W-2 clone of P. falciparum.

  DOI：

  10.1021/jm010549o

文献信息

• Method of reducing blood glucose
  申请人：Novo Nordisk A/S

  公开号：US05741791A1

  公开（公告）日：1998-04-21

  The present invention relates to the use of compounds of the general formula ##STR1## for reducing blood glucose and/or inhibit the secretion, circulation or effect of insulin antagonizing peptides like CGRP or amylin. Hence the compound can be used in the treatment of insulin resistance related to NIDDM (non-insulin-dependent diabetes mellitus) or aging.

  本发明涉及使用一般式##STR1##的化合物来降低血糖和/或抑制胰岛素拮抗肽如CGRP或淀粉样蛋白的分泌、循环或作用。因此，该化合物可用于治疗与NIDDM（非胰岛素依赖型糖尿病）或衰老相关的胰岛素抵抗。
• N-substituted azaheterocyclic carboxylic acids and esters thereof
  申请人：Novo Nordisk A/S

  公开号：US05595989A1

  公开（公告）日：1997-01-21

  The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

  本发明涉及新颖的N-取代的氮杂环羧酸及其酯，其中取代烷基链构成N-取代物的一部分或其盐，以及它们的制备方法，含有它们的组合物，以及它们在临床治疗疼痛、过敏性疼痛和/或炎症病况中的应用，其中C-纤维通过引发神经源性疼痛或炎症发挥病理生理作用。
• [EN] NOVEL METHOD<br/>[FR] NOUVEAU PROCEDE
  申请人：NOVO NORDISK A/S

  公开号：WO1997022338A1

  公开（公告）日：1997-06-26

  (EN) The present invention relates to the use of compounds of general formula (I) for reducing blood glucose and/or inhibit the secretion, circulation or effect of isulin antagonizing peptides like CGRP or amylin. Hence the compound can be used in the treatment of insulin resistance related to NIDDM (non-insulin-dependent diabetes mellitus) or aging.(FR) La présente invention se rapporte à l'utilisation de composés de la formule générale (I) pour réduire le taux de glycémie et/ou inhiber la sécrétion, la circulation ou l'effet de peptides antagonistes de l'insuline tels que CGRP ou l'amyline. Ce composé peut par conséquent être utilisé pour le traitement de l'insulinorésistance associée au diabète sucré non insulino-dépendant (NIDDM) ou au vieillissement.

  (中) 本发明涉及使用一般式（I）的化合物来降低血糖和/或抑制分泌、循环或作用于类胰岛素拮抗肽如CGRP或淀粉样蛋白。因此，该化合物可用于治疗与NIDDM（非胰岛素依赖性糖尿病）或衰老相关的胰岛素抵抗。
• [EN] NOVEL HETEROCYCLIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES HETEROCYCLIQUES
  申请人：NOVO NORDISK A/S

  公开号：WO1995018793A1

  公开（公告）日：1995-07-13

  (EN) The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof (I) in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.(FR) L'invention concerne de nouveaux acides carboxyliques azahétérocycliques substitués en N et leurs esters de la formule (I), dans laquelle une chaîne alkyle substitué fait partie intégrante du substituant en N ou de ses sels. L'invention concerne en outre des procédés permettant de préparer ces composés, des compositions les contenant, ainsi que leur utilisation dans le traitement clinique d'états douloureux, des hyperalgésies et/ou des états inflammatoires, dans lesquels les fibres de type C ont un rôle déterminant en terme de pathophysiologie, dans la mesure où elles induisent la douleur ou l'inflammation neurogène.

  本发明涉及新型N-取代的杂环羧酸和其酯（I），其中取代烷基链形成N-取代物的一部分或其盐，以及制备它们的方法，包含它们的组合物，以及它们在临床治疗痛苦、高敏感和/或炎症病症中的使用，其中C纤维通过引起神经源性疼痛或炎症发挥病理生理学作用。
• N-substituted azaheterocyclic carboxlic acids and esters thereof
  申请人：Novo Nordisk A/S

  公开号：US05795888A1

  公开（公告）日：1998-08-18

  The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

  本发明涉及一种新型N取代的杂环羧酸和其酯类，其中N取代基的取代烷基链或其盐，以及制备它们的方法，包含它们的组合物，以及它们在临床治疗中用于治疗C纤维引起的神经源性疼痛或炎症的疼痛，过度疼痛和/或炎症条件。