他齐茶碱 | 79712-55-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 他齐茶碱
• 英文名称: 3,7-dihydro-1,3-dimethyl-7-<3-<4-<3-(phenylthio)propyl>piperazin-1-yl>-2-hydroxypropyl>-1H-purine-2,6-dione
• 英文别名: 7-[3-[4-(3-phenylthiopropyl)-1-piperazinyl]-2-hydroxypropyl]-theophylline；tazifylline；3,7-dihydro-1,3-dimethyl-7-(3-{4-[3-(phenylthio)propyl]piperazin-1-yl}-2-hydroxypropyl)-1H-purine-2,6-dione；7-[2-hydroxy-3-[4-(3-phenylsulfanylpropyl)piperazin-1-yl]propyl]-1,3-dimethylpurine-2,6-dione
• CAS: 79712-55-3；113932-15-3；113932-16-4
• 化学式: C₂₃H₃₂N₆O₃S
• 分子量: 472.611
• InChiKey: JTOUASWUIMAMAD-UHFFFAOYSA-N

物化性质

• 沸点：
  705.1±70.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

制备方法与用途

生物活性

(-)-Tazifylline 是一种有效的、选择性的长效组胺 H1 受体拮抗剂。

靶点

• H1-receptor

体外研究

Tazifylline 能强烈抑制由组胺 H1 受体刺激引起的平滑肌收缩，在孤立的豚鼠回肠中表现出高亲和力。在体外放射配体结合实验中，它对组胺 H2 受体、α 和 β-肾上腺素受体、5-羟色胺以及胆碱能受体亚型的亲和力较低。Tazifylline 对大鼠腹膜肥大细胞释放组胺的作用微弱。

体内研究

在大鼠、豚鼠和狗中，Tazifylline 的抗组胺作用迅速起效且持续时间长。在麻醉豚鼠中，它显著抑制组胺引起的支气管收缩，并保护清醒动物免受大量组胺的致命影响。在清醒的大鼠中，Tazifylline 在减少皮肤炎症反应方面比过敏性反应更为有效。口服给予 Tazifylline 可长时间抑制豚鼠由组胺引起的皮肤炎症，麻醉动物中则减轻了与 H1-受体激活相关的部分血压下降。大量口服 Tazifylline 并不会降低小鼠的自发活动力，也不会在清醒大鼠中引起明显的行为抑郁症状。

反应信息

• 作为反应物：
  描述：

  他齐茶碱 生成 7-[3-[4-[3-(benzenesulfinyl)propyl]piperazin-1-yl]-2-hydroxypropyl]-1,3-dimethylpurine-2,6-dione;hydrochloride
  参考文献：
  名称：

  BERANGER, SERGE;PASCAL, J. CLAUDE;PINHAS, HENRI;JULLIEN, ISABELLE

  摘要：

  DOI：
• 作为产物：
  描述：

  3-氯丙基苯基硫醚 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 27.0h， 生成 他齐茶碱
  参考文献：
  名称：

  New Antihistaminic Theophylline or Theobromine Derivatives

  摘要：

  A series of 3,4-dihydro-1,3-dimethyl-7-[3-(4-substituted-piperazin-1-yl)- substituted-alkyl]-1H-purine-2,6-diones and 3,7-dihydro-3,7-dimethyl-1-[3-(4-substituted-piperazin-1-yl)- substituted-alkyl]-1H-purine-2,6-diones was synthesized and evaluated for antihistaminic activity. Some of them displayed good inhibition of both histamine-induced bronchospasm in the anesthetized guinea pig at 10 micrograms/kg by the intravenous route and of passive cutaneous anaphylaxis in the rat at 10 mg/kg by the oral route. Comparison of the two most active compounds revealed a higher antihistaminic activity with the compounds containing a (phenylthio)propyl group (1 and 2) as compared with that containing a phenoxy group. Compound 2 [RS-49014, 3,4-dihydro-1,3-dimethyl-7-[3-[4-[3-(phenylthio)propyl]piperazin-1 -yl]- 2-hydroxypropyl]-1H-purine-2,6-dione] was selected for clinical trials on the basis of a comparative pharmacological study with chlorpheniramine, ketotifen, promethazine, and theophylline.

  DOI：

  10.1021/jm50001a019

文献信息

• 5-memberd heteroaryl substituted 1,4-dihydropyridine compounds as bradykinin antagonists
  申请人：——

  公开号：US20010046993A1

  公开（公告）日：2001-11-29

  This invention provides a compound of the formula (I): 1 or the pharmaceutically acceptable salts thereof wherein A is independently halo; Y 1 is —(CH 2 ) m —, C(O) or S(O); Y 2 is N or CH; R 1 and R 2 are independently C 1-4 alkyl; R 3 is selected from the following: (a) optionally substituted —(CH 2 ) p —C 3-7 cycloalkyl; (b) optionally substituted —C 5-7 alkyl; and (c) substituted —C 1-4 alkyl; and (d) optionally substituted C 7- bicycloalkyl; R 4 is optionally substituted thiazolyl, imidazolyl or oxazolyl; X is S, —NH, —N—C 1-4 alkyl or O; R 5 is hydrogen or C 1-4 alkyl; R 6 is C 1-4 alkyl or halo; m is 0, 1 or 2; n is 0, 1, 2, 3, 4 or S; and p is 0, 1, 2, 3, 4, 5 or 6. These compounds are useful for the treatment of medical conditions caused by bradykinin such as inflammation, cardiovascular disease, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了以下式(I)的化合物或其药学上可接受的盐，其中A独立地是卤素；Y1是—(CH2)m—、C(O)或S(O)；Y2是N或CH；R1和R2独立地是C1-4烷基；R3从以下选项中选择：(a) 可选地取代的—(CH2)p—C3-7环烷基；(b) 可选地取代的—C5-7烷基；以及(c) 取代的—C1-4烷基；和(d) 可选地取代的C7双环烷基；R4是可选地取代的噻唑基、咪唑基或噁唑基；X是S、—NH、—N—C1-4烷基或O；R5是氢或C1-4烷基；R6是C1-4烷基或卤素；m是0、1或2；n是0、1、2、3、4或S；p是0、1、2、3、4、5或6。这些化合物可用于治疗由激肽酶引起的医疗状况，如炎症、心血管疾病、疼痛等。该发明还提供了包含上述化合物的药物组合物。
• Substituted 1,4-dihydropyridine compounds as bradykinin antagonists
  申请人：——

  公开号：US20020042421A1

  公开（公告）日：2002-04-11

  This invention provides a compound of the formula (I): 1 or the pharmaceutically acceptable salts thereof wherein A is independently halo; Y is —(CH 2 ) m— , —C(O)— or —S(O)—; R 1 and R 2 are independently C 1-4 alkyl; R 3 is C 7-9 bicycloalkyl, C 5-7 azacycloalkyl or C 7-9 azabicycloalkyl, the C 7-9 bicycloalkyl, C 5-7 azacycloalkyl or C 7-9 azabicycloalkyl being optionally substituted with one, two or three substituents are independently selected from oxo, hydroxyl, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkyl-carbonyl, formyl, C 1-4 alkylenedioxy, and phenyl-C 1-4 alkyl; R 4 is thiazolyl, imidazolyl or oxazolyl, the thiazolyl, imidazolyl or oxazolyl being optionally substituted with one or two substituents independently selected from C 1-4 alkyl and halo; R 5 is hydrogen or C 1-4 alkyl;m is 0, 1 or 2; and n is 0, 1, 2, 3, 4 or 5. These compounds are usefuil for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了以下式（I）的化合物或其药学上可接受的盐，其中A独立表示卤素；Y为—（CH2）m—，—C(O)—或—S(O)—；R1和R2独立表示C1-4烷基；R3为C7-9双环烷基，C5-7杂环烷基或C7-9杂双环烷基，其中C7-9双环烷基，C5-7杂环烷基或C7-9杂双环烷基可以选择性地被一个、两个或三个取代基取代，这些取代基独立地选自氧代、羟基、C1-4烷基、C1-4烷氧基、C1-4烷基羰基、甲酰基、C1-4烷基二氧基和苯基-C1-4烷基；R4为噻唑基、咪唑基或氧唑基，其中噻唑基、咪唑基或氧唑基可以选择性地被一个或两个取代基独立地选自C1-4烷基和卤素取代；R5为氢或C1-4烷基；m为0、1或2；n为0、1、2、3、4或5。这些化合物可用于治疗由激肽酶介导的医疗状况，如炎症、过敏性鼻炎、疼痛等。这项发明还提供了包含上述化合物的药物组合物。
• N-benzenesulfonyl l-proline compounds as bradykinin antagonists
  申请人：Pfizer Inc.

  公开号：US20020128271A1

  公开（公告）日：2002-09-12

  This invention provides a compound of the formula (I): 1 or the pharmaceutically acceptable salts thereof wherein X 1 and X 2 are halo; R 1 and R 2 are independently hydrogen or C 1-4 alkyl; R 3 and R 4 are each hydrogen or halo; and R 5 is (a) —C 3-9 diazacycloalkyl optionally substituted with C 5-11 azabicycloalkyl; (b) —C 3-9 azacycloalkyl-NH—(C 5-11 azabicycloalkyl optionally substituted with C 1-4 alkyl); (c) —NH—C 1-3 alkyl-C(O)—C 5-11 diazabicycloalkyl; (d) —NH—C 1-3 alkyl-C(O)—NH—C 5-11 azabicycloalkyl, the C 5-11 azabicycloalkyl being optionally substituted with C 1-4 alkyl; (e) —C 3-9 azacycloalkyl optionally substituted with C 3-9 azacycloalkyl; or (f) —NH—C 1-5 alkyl-NH—C(O)—C 4-9 cycloalkyl-NH 2 . These compounds are useful for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了式(I)的化合物：1或其药学上可接受的盐，其中X1和X2是卤素；R1和R2分别是氢或C1-4烷基；R3和R4分别是氢或卤素；以及R5是(a) -C3-9二氮杂环烷基，可选择地取代为C5-11氮杂双环烷基；(b) -C3-9氮杂环烷基-NH-(可选择地取代为C1-4烷基的C5-11氮杂双环烷基)；(c) -NH-C1-3烷基-C(O)-C5-11二氮杂双环烷基；(d) -NH-C1-3烷基-C(O)-NH-C5-11氮杂双环烷基，C5-11氮杂双环烷基可选择地取代为C1-4烷基；(e) -C3-9氮杂环烷基，可选择地取代为C3-9氮杂环烷基；或(f) -NH-C1-5烷基-NH-C(O)-C4-9环烷基-NH2。这些化合物对于治疗由激肽酶介导的医疗状况如炎症、过敏性鼻炎、疼痛等是有用的。这项发明还提供了包含上述化合物的药物组合物。
• Piperazine derivatives of theophylline
  申请人：Laroche-Navarron, S.A.

  公开号：US04374835A1

  公开（公告）日：1983-02-22

  New compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein Z.sub.1 and Z.sub.2 are each independently selected from the group consisting of CH.sub.2, CHOB and C.dbd.O, wherein B is selected from the group consisting of hydrogen and alkanoyl; Y is oxygen or sulfur; n is an integer from 0-4 but cannot be zero when Z.sub.1 is CHOB; m is an integer from 0-4 but cannot be zero when Z.sub.2 is CHOB; and R.sub.1, R.sub.2 and R.sub.3 are each independently hydrogen, halogen, hydroxy, trifluoromethyl, alkyl or alkoxy; are antihistamines and are therefore useful in the treatment of respiratory diseases including asthma, hay fever, allergies and the common cold.

  该公式的新化合物为##STR1##及其药用可接受的酸盐，其中Z.sub.1和Z.sub.2分别独立地选自CH.sub.2、CHOB和C.dbd.O组成的群，其中B选自氢和烷酰基组成的群；Y为氧或硫；n为0-4之间的整数，但当Z.sub.1为CHOB时不能为零；m为0-4之间的整数，但当Z.sub.2为CHOB时不能为零；R.sub.1、R.sub.2和R.sub.3分别独立地为氢、卤素、羟基、三氟甲基、烷基或烷氧基；它们是抗组胺药物，因此在治疗呼吸道疾病包括哮喘、花粉热、过敏和感冒方面具有用处。
• Pharmaceutical preparation comprising an active dispersed on a matrix
  申请人：——

  公开号：US20040058896A1

  公开（公告）日：2004-03-25

  The present invention relates to the field of pharmaceutical technology and describes a novel advantageous preparation for an active ingredient. The novel preparation is suitable for producing a large number of pharmaceutical dosage forms. In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix composed of one or more excipients selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid ester.

  本发明涉及制药技术领域，描述了一种新的有利的活性成分制备方法。这种新的制备方法适用于生产大量的药物剂型。在这种新的制备方法中，活性成分基本上均匀地分散在由脂肪醇、甘油三酯、部分甘油酯和脂肪酸酯等多种赋形剂中选择的一种或多种赋形剂组成的赋形剂基质中。