盐酸普拉克索

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 盐酸普拉克索
• 中文别名: 普拉克索二盐酸一水合物；(S)-2-氨基-4,5,6,7-四氢-6-(丙基氨基)苯并噻唑二盐酸盐一水合物；(S)-2-氨基-4,5,6,7-四氢-6-(丙氨基)苯并噻唑二盐酸盐；普拉克索；盐酸普拉克索水合物
• 英文名称: hydron;(6S)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dichloride;hydrate
• 化学式: C10H21Cl2N3OS
• mdl: MFCD02183927
• 分子量: 302.3
• InChiKey: APVQOOKHDZVJEX-QTPLPEIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  80.2
• 氢给体数：
  5
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

母乳喂养期间使用总结：目前没有关于在哺乳期间使用普拉克索的信息，但它抑制血清催乳素，可能会干扰哺乳。在哺乳新生儿或早产儿时，可能更愿意选择另一种药物。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，在哺乳母亲中没有找到相关的已发布信息。普拉克索降低血清催乳素水平。[1] 对于已经建立泌乳的母亲，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:No information is available on the use of pramipexole during breastfeeding, but it suppresses serum prolactin and may interfere with breastfeeding. An alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information in nursing mothers was not found as of the revision date. Pramipexole lowers serum prolactin.[1] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为产物：
  描述：

  s-2-氨基-6-丙酰氨基-4,5,6,7-四氢苯并噻唑 以>96% ee; 50的产率得到盐酸普拉克索
  参考文献：
  名称：

  Tetrahydro-benzthiazoles, the preparation thereof and their use as

  摘要：

  本发明涉及一种新的四氢苯并噻唑通式##STR1##其中R.sub.1表示氢原子、烷基、烯基或炔基、脂肪酰基、苯基烷基或苯基脂肪酰基，上述提到的苯基核可以被1或2个卤素原子取代，R.sub.2表示氢原子或烷基，R.sub.3表示氢原子、烷基、环烷基、烯基或炔基、脂肪酰基、苯基烷基或苯基脂肪酰基，而苯基核可以被氟、氯或溴原子取代，R.sub.4表示氢原子、烷基、烯基或炔基，或R.sub.3和R.sub.4与它们之间的氮原子一起表示吡咯啉基、哌啶基、六亚甲基亚胺基或吗啉基，其对映异构体和酸盐。通式I中的化合物，其中R.sub.1或R.sub.3或R.sub.1和R.sub.3中的一个表示酰基，是制备具有有价值的药理学性质的通式I中的其他化合物的有价值的中间体。可以使用已知的方法制备新化合物。

  公开号：

  US04886812A1

文献信息

• Tetrahydro-benzthiazoles, the preparation thereof and their use as
  申请人：Dr. Karl Thomae GmbH

  公开号：US04886812A1

  公开（公告）日：1989-12-12

  This invention relates to new tetrahydrobenzthiazoles of general formula ##STR1## wherein R.sub.1 represents a hydrogen atom, an alkyl group, an alkenyl or alkynyl group, an alkanoyl group, a phenyl alkyl or phenyl alkanoyl group, while the above mentioned phenyl nucleic may each be substituted by 1 or 2 halogen atoms, R.sub.2 represents a hydrogen atom or an alkyl group, R.sub.3 represents a hydrogen atom, an alkyl group a cycloalkyl group, an alkenyl or alkynyl group, an alkanoyl group, a phenyl alkyl or phenyl alkanoyl group, while the phenyl nucleus may be substituted by fluorine, chlorine or bromine atoms, R.sub.4 represents a hydrogen atom, an alkyl group, an alkyl or alkenyl group, or R.sub.3 and R.sub.4 together with the nitrogen atom between them represent a pyrrolidino, piperidino, hexamethyleneimino or morpholino group, the enantiomers and the acid addition salts thereof. The compounds of general formula I above in which one of the groups R.sub.1 or R.sub.3 or both groups R.sub.1 and R.sub.3 represent an acyl group are valuable intermediate products for preparing the other compounds of general formula I which have valuable pharmacological properties. The new compounds may be prepared using methods known per se.

  本发明涉及一种新的四氢苯并噻唑通式##STR1##其中R.sub.1表示氢原子、烷基、烯基或炔基、脂肪酰基、苯基烷基或苯基脂肪酰基，上述提到的苯基核可以被1或2个卤素原子取代，R.sub.2表示氢原子或烷基，R.sub.3表示氢原子、烷基、环烷基、烯基或炔基、脂肪酰基、苯基烷基或苯基脂肪酰基，而苯基核可以被氟、氯或溴原子取代，R.sub.4表示氢原子、烷基、烯基或炔基，或R.sub.3和R.sub.4与它们之间的氮原子一起表示吡咯啉基、哌啶基、六亚甲基亚胺基或吗啉基，其对映异构体和酸盐。通式I中的化合物，其中R.sub.1或R.sub.3或R.sub.1和R.sub.3中的一个表示酰基，是制备具有有价值的药理学性质的通式I中的其他化合物的有价值的中间体。可以使用已知的方法制备新化合物。
• Process for the preparation of biologically active tetrahydrobenzthiazole derivative
  申请人：Mistry N. Dhiren

  公开号：US20070123573A1

  公开（公告）日：2007-05-31

  Improved process for the preparation of the intermediate compound of formula II for formation of biological active tetrahydrobenzothiazole compound of formula (I) as well as the biological active tetrahydrobenzothiazole compound of formula (I) and/or its pharmaceutically acceptable salts or solvates. The process comprises reacting 4-amino cyclohexanol of formula (III) or its acid addition salts with phthalic anhydride in presence of acid catalyst and their salts, in polar aprotic solvent or its mixture with organic solvent, capable of removing water azeotropically to give 4-(phthalimido)-cyclohexanol of formula (IV); oxidizing 4-(phthalimido)-cyclohexanol of formula (IV) to give 4-(phthalimido)-cyclohexanone of formula (V); brominating 4-(phthalimido)-cyclohexanone of formula (V) with brominating agent in organic solvent in presence of Lewis acid catalyst to prepare 2-bromo-4-(phthalimido)-cyclohexanone of formula (VI); treating 2-bromo-4-(phthalimido)-cyclohexanone of formula (VI) with thiourea in organic solvent in presence of base to give 2-amino-6-phthalimido-4,5,6,7-tetrahydro benzothiazol of formula (VII); reacting compound of formula (VII) with hydrazine hydrate and base in polar solvent to give racemic 2,6-diamino-4,5,6,7-tetrahydro-1,3-benzothiazole of formula (VIII); resolving racemic 2,6-diamino-4,5,6,7-tetrahydro-1,3-benzothiazole of formula (VIII) to prepare (6S)-2,6-diamino-4,5,6,7-tetrahydro-1,3-benzothiazole of formula (II). To form the compound of Formula I and if desired its salts/solvates the above process is carried out with further steps of coupling (6S)-2,6-dimino-4,5,6,7-tetrahydro-1,3-benzothiazole of formula (II) with propionaldehyde in presence of mineral acid in polar organic solvent and reducing agent to prepare (S)-(−)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I);and if desired converting (S)-(−)-2-Amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole to its pharmaceutically acceptable salts or solvates.

  改进的制备中间化合物II的工艺，用于制备生物活性四氢苯并噻唑化合物I，以及生物活性四氢苯并噻唑化合物I和/或其药学上可接受的盐或溶剂。该工艺包括在极性无水溶剂或其与有机溶剂的混合物中，与酸催化剂及其盐共同反应式III的4-氨基环己醇或其酸加成盐与邻苯二酸酐，能够共沸去除水的极性无水溶剂或其混合物，以给出式IV的4-(邻苯二酰亚胺)-环己醇；将式IV的4-(邻苯二酰亚胺)-环己醇氧化为式V的4-(邻苯二酰亚胺)-环己酮；在有机溶剂中，在路易斯酸催化剂的存在下，用溴化剂溴化式V的4-(邻苯二酰亚胺)-环己酮，以制备式VI的2-溴-4-(邻苯二酰亚胺)-环己酮；在碱的存在下，在有机溶剂中用硫脲处理式VI的2-溴-4-(邻苯二酰亚胺)-环己酮，以给出式VII的2-氨基-6-邻苯二酰亚胺-4,5,6,7-四氢苯并噻唑；在极性溶剂中，用肼水合物和碱反应式VII的化合物，以给出式VIII的外消旋2,6-二氨基-4,5,6,7-四氢-1,3-苯并噻唑；分离外消旋2,6-二氨基-4,5,6,7-四氢-1,3-苯并噻唑，制备式II的(6S)-2,6-二氨基-4,5,6,7-四氢-1,3-苯并噻唑。为了形成式I的化合物，如果需要其盐/溶剂，以上工艺还需进行以下步骤：在极性有机溶剂和还原剂的存在下，将(6S)-2,6-二氨基-4,5,6,7-四氢-1,3-苯并噻唑II与丙醛在矿物酸的存在下偶联，以制备式I的(S)-(−)-2-氨基-6-(n-丙基氨基)-4,5,6,7-四氢苯并噻唑；如果需要，将(S)-(−)-2-氨基-6-(n-丙基氨基)-4,5,6,7-四氢苯并噻唑转化为其药学上可接受的盐或溶剂。
• PROCESS FOR THE PREPARATION OF PRAMIPEXOLE BASE AND/OR ITS SALTS
  申请人：BALICKI Roman

  公开号：US20090105483A1

  公开（公告）日：2009-04-23

  The process for the preparation of pramipexole base and/or its pharmaceutically acceptable salts, especially the hydrochloride salt, in the alkylation reaction of (S)-(−)2,6-diamino-4,5,6,7-tetrahydrobenzothiazole with an alkylating agent, wherein the reaction is carried out in the absence of a base, and in a solvent from which the resulting N-monoalkylated product selectively precipitates out as a salt. After isolation from the reaction mixture, the N-monoalkylated product is converted a) into the free pramipexole base upon treatment with an inorganic base and is then converted into another pharmaceutically acceptable pramipexole salt; or b) directly into another pharmaceutically acceptable pramipexole salt or the hydrate thereof.

  制备普拉莫尔碱和/或其药学上可接受的盐，特别是盐酸盐的过程，在(S)-(-)2,6-二氨基-4,5,6,7-四氢苯并噻唑与烷基化剂的烷基化反应中进行，其中反应在无碱的情况下，在溶剂中进行，从中选择性地沉淀出N-单烷基化产物作为盐。从反应混合物中分离后，N-单烷基化产物转化为a)与无机碱处理后转化为自由普拉莫尔碱，然后转化为另一种药学上可接受的普拉莫尔盐；或b)直接转化为另一种药学上可接受的普拉莫尔盐或其水合物。
• WO2008041240A1
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• WO2008097203A1
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