马吲哚 | 22232-71-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 马吲哚
• 中文别名: 美新达；5-(4-氯苯基)-2,3-二氢-5-羟基-5H-咪唑并[2,1-a]异吲哚
• 英文名称: Mazindol
• 英文别名: 5-(4-chlorophenyl)-2,3-dihydroimidazo[1,2-b]isoindol-5-ol
• CAS: 22232-71-9
• 化学式: C₁₆H₁₃ClN₂O
• 分子量: 284.745
• InChiKey: ZPXSCAKFGYXMGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

在大鼠、狗和人体尿液中主要代谢物：5-(对氯苯基)-2,5-二氢-5-羟基-(3)H-咪唑(2,1-α)异吲哚-3-酮。

Major metabolite in urine in rat, dog, and human: 5-(para-chlorophenyl)-2,5-dihydro-5-hydroxy-(3)h-imidazo(2,1-alpha)isoindol-3-o.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏的。半衰期：10-13小时

Hepatic. Half Life: 10-13 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尽管拟交感神经药物在治疗肥胖症中的作用机制尚未完全了解，但这些药物具有与安非他命相似的药理作用。与其它拟交感神经食欲抑制剂（如芬特明）不同，马吲哚被认为是通过抑制去甲肾上腺素的再摄取，而不是促进其释放。

Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Unlike other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to inhibit the reuptake of norepinephrine rather than to cause its release.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

使用大量这些药物可能导致一种称为amphetamine psychosis（致幻剂精神障碍）的状况，这可能导致听觉、视觉和触觉幻觉、强烈的偏执、不合理的思想和信念、妄想以及精神混乱。

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

马吲哚过量症状包括焦虑不安、震颤、呼吸急促、混乱、幻觉、恐慌、攻击性、恶心、呕吐、腹泻、心律不齐和癫痫发作。

Symptoms of a mazindol overdose include restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

同时使用其他产生中枢神经系统刺激的药物或甲状腺激素与食欲抑制剂可能会增加这些药物或食欲抑制剂的中枢神经系统刺激作用。/食欲抑制剂，拟交感神经药/

Concurrent use /of other CNS stimulation-producing medications or thyroid hormones with appetite suppressants/ may increase the CNS stimulant effects of either these medications or the appetite suppressant. /Appetite suppressants, sympathomimetic/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次口服2毫克剂量产生峰值血药浓度为2.5纳克/毫升，持续6小时。多次剂量，每天3次，每次2毫克，连续4天，在第4天最后一次给药后2小时达到最大浓度10.8纳克/毫升。

Single oral dose of 2-mg produced peak blood level of 2.5 ng/mL, for 6 hr. Multiple doses 2-mg 3/day for 4 days caused max concentration of 10.8 ng/mL 2 hr following last dose on day 4.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

主要在尿液中以未改变的药物和结合型代谢物形式排出。

Excreted primarily in the urine as unchanged drug and conjugated metabolites.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给药后，马辛多尔（mazindol）从胃肠道容易被吸收。该药物的起效时间为30-60分钟，作用持续时间为8-15小时。据报道，治疗有效的血药浓度为3-12 ng/mL，推荐剂量下达到的血药浓度为2-4 ng/mL。马辛多尔主要以原型药物和结合代谢物的形式通过尿液排泄。

Following oral administration, mazindol is readily absorbed from the GI tract. The drug has an onset of action of 30-60 minutes and a duration of action of 8-15 hours. Therapeutically effective blood concentrations reportedly are 3-12 ng/mL, and blood concentrations achieved with recommended dosage are 2-4 ng/mL. Mazindol is excreted primarily in urine as unchanged drug and conjugated metabolites.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  马吲哚 以 乙醇 为溶剂， 生成 4'-chloro-2-(imidazolin-2-yl)benzophenone hydrochloride
  参考文献：
  名称：

  Imidazolinyl phenyl carbonyl compounds acid addition salts and related

  摘要：

  这项发明涉及四氢嘧啶基苯甲酰酸盐、咪唑啉基苯甲酰酸盐、二氢咪唑异喹酮、四氢嘧啶异喹酮和四氢嘧啶异喹酮酸盐，它们在药理学上具有抗抑郁作用。四氢嘧啶基苯甲酰酸盐、四氢嘧啶异喹酮和四氢嘧啶异喹酮酸盐还具有利尿作用，而咪唑啉基苯甲酰酸盐和二氢咪唑异喹酮具有压食作用。这项发明还涉及几种制备这些化合物的方法。

  公开号：

  US03935218A1
• 作为产物：
  描述：

  9beta-(4-氯苯基)-1,2,3,9beta-四氢-5H-咪唑并[2,1-a]异吲哚-5-酮 在 吡啶 作用下， 以 硫酸 为溶剂， 生成 马吲哚
  参考文献：
  名称：

  Imidazolinyl phenyl carbonyl compounds acid addition salts and related

  摘要：

  这项发明涉及四氢嘧啶基苯甲酰酸盐、咪唑啉基苯甲酰酸盐、二氢咪唑异喹酮、四氢嘧啶异喹酮和四氢嘧啶异喹酮酸盐，它们在药理学上具有抗抑郁作用。四氢嘧啶基苯甲酰酸盐、四氢嘧啶异喹酮和四氢嘧啶异喹酮酸盐还具有利尿作用，而咪唑啉基苯甲酰酸盐和二氢咪唑异喹酮具有压食作用。这项发明还涉及几种制备这些化合物的方法。

  公开号：

  US03935218A1

文献信息

• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• [EN] HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF STRESS-RELATED CONDITIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES POUR LE TRAITEMENT D'ÉTATS LIÉS AU STRESS
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2010137738A1

  公开（公告）日：2010-12-02

  The present invention provides a novel heterocyclic compound. A heterocyclic compound represented by general formula (1) wherein, R1 and R2, each independently represent hydrogen; a phenyl lower alkyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and the like on a benzene ring and/or a lower alkyl group; or a cyclo C3-C8 alkyl lower alkyl group; or the like; R3 represents a lower alkynyl group or the like; R4 represents a phenyl group that may have a substituent(s) selected from the group consisting of a 1,3,4-oxadiazolyl group that may have e.g., halogen or a heterocyclic group selected from pyridyl group and the like; the heterocyclic group may have at least one substituent(s) selected from a lower alkoxy group and the like or a salt thereof.

  本发明提供了一种新颖的杂环化合物。一种由通式（1）表示的杂环化合物，其中，R1和R2分别独立表示氢；苯基较低烷基基团，可能在苯环和/或较低烷基基团上具有从较低烷基基团等组成的取代基；或环C3-C8烷基较低烷基基团；或类似物；R3表示较低炔基基团或类似物；R4表示可能具有从1,3,4-噁二唑基团（例如，卤素）或从吡啶基团等组成的取代基的苯基团；所述杂环基可能具有至少一个从较低烷氧基等选择的取代基或其盐。
• Melanocortin-4 receptor binding compounds and methods of use thereof
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040082779A1

  公开（公告）日：2004-04-29

  Provided are MC4-R binding compounds of the formula XVII: 1 wherein L 2 is a linker group, and P 1 , P 2 , P 3 , P 4 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , t, s, and R are as described in the specification. Methods of using the compounds to treat MC4-R associated disorders, such as disorders associated with weight loss, are also provided.

  提供了具有以下化学式XVII的MC4-R结合化合物： 其中L2是连接基团，P1、P2、P3、P4、Z1、Z2、Z3、Z4、Z5、t、s和R如规范中所述。还提供了使用这些化合物治疗与MC4-R相关疾病的方法，例如与体重减轻相关的疾病。
• [EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK AS

  公开号：WO2005105736A1

  公开（公告）日：2005-11-10

  Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

  通用公式（I）的新化合物，这些化合物作为药物组成部分的用途，包括这些化合物的药物组成部分和使用这些化合物和组成部分的治疗方法。这些化合物可能在治疗和/或预防由过氧化物酶体增殖物激活受体（PPAR）介导的疾病中有用，特别是PPARδ亚型。

表征谱图