5-((benzhydrylsulfinyl)methyl)thiazole | 1879038-73-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-((benzhydrylsulfinyl)methyl)thiazole
• 英文别名: CE-123；5-(benzhydrylsulfinylmethyl)-1,3-thiazole
• CAS: 1879038-73-9
• 化学式: C₁₇H₁₅NOS₂
• 分子量: 313.444
• InChiKey: VBBBWHDWYLUSEL-UHFFFAOYSA-N

物化性质

• 沸点：
  555.6±50.0 °C(Predicted)
• 密度：
  1.311±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-((diphenylmethylthio)methyl)thiazole 在 双氧水 、 溶剂黄146 作用下， 反应 12.0h， 以50.2%的产率得到5-((benzhydrylsulfinyl)methyl)thiazole
  参考文献：
  名称：

  A daily single dose of a novel modafinil analogue CE-123 improves memory acquisition and memory retrieval

  摘要：

  Dopamine reuptake inhibitors have been shown to improve cognitive parameters in various tasks and animal models. We recently reported a series of modafinil analogues, of which the most promising, 5-((benzhydrylsulfinyl)methyl) thiazole (CE-123), was selected for further development. The present study aims to characterize pharmacological properties of CE-123 and to investigate the potential to enhance memory performance in a rat model. In vitro transporter assays were performed in cells expressing human transporters. CE-123 blocked uptake of [3H] dopamine (IC50 = 4.606 mu M) while effects on serotonin (SERT) and the norepinephrine transporter (NET) were negligible. Blood-brain barrier and pharmacokinetic studies showed that the compound reached the brain and lower elimination than R-modafinil. The Pro-cognitive effect was evaluated in a spatial hole-board task in male Sprague-Dawley rats and CE-123 enhances memory acquisition and memory retrieval, represented by significantly increased reference memory indices and shortened latency. Since DAT blockers can be considered as indirect dopamine receptor agonists, western blotting was used to quantify protein levels of dopamine receptors D1R, D2R and D5R and DAT in the synaptosomal fraction of hippocampal subregions CA1, CA3 and dentate gyms (DG). CE-123 administration in rats increased total DAT levels and D1R protein levels were significantly increased in CA1 and CA3 in treated/trained groups. The increase of D5R was observed in DG only. Dopamine receptors, particularly D1R, seem to play a role in mediating CE-123-induced memory enhancement. Dopamine reuptake inhibition by CE-123 may represent a novel and improved stimulant therapeutic for impairments of cognitive functions.

  DOI：

  10.1016/j.bbr.2018.01.032

文献信息

• [EN] HETEROCYCLIC COMPOUNDS WITH WORKING MEMORY ENHANCING ACTIVITY<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES À ACTIVITÉ AMÉLIORANT LA MÉMOIRE DE TRAVAIL
  申请人：RED BULL GMBH

  公开号：WO2016023997A1

  公开（公告）日：2016-02-18

  The present invention relates to a chemical compound having the general formula (I): wherein R1 and R2 are, equal or independently, aryl, heteroaryl; wherein RTA is a 2-1,3-, or 4- 1,3- or 5-1,3-thiazole ring and its use in for improving; the short term memory and/or the working memory.

  本发明涉及一种具有通式(I)的化合物，其中R1和R2分别或相等地为芳基、杂环芳基；其中RTA为2-1、3-、或4-1、3-或5-1、3-噻唑环，以及其在改善短期记忆和/或工作记忆方面的用途。
• [EN] (S)-ENANTIOMERIC FORM OF A HETEROCYCLIC COMPOUND HAVING MOTIVATION IMPROVING AND/OR REFERENCE MEMORY ENHANCING ACTIVITY<br/>[FR] FORME (S)-ÉNANTIOMÈRE D'UN COMPOSÉ HÉTÉROCYCLIQUE AYANT UNE ACTIVITÉ D'AMÉLIORATION DE LA MOTIVATION ET/OU D'AMÉLIORATION DE LA MÉMOIRE DE RÉFÉRENCE
  申请人：RED BULL GMBH

  公开号：WO2019197670A1

  公开（公告）日：2019-10-17

  The present invention relates to the (S)-enantiomer of the chemical compound having the general formula (I); formula (I) wherein R1, and R2 are, equal or independently, aryl, heteroaryl, fused aryl, fused heteroaryl, mono or multi-substituted aryl, mono or multi-substituted heteroaryl, mono or multi- substituted fused and, mono or multi-substituted fused heteroaryl; and RTA is a 2-1,3-, or 4~ 1,3- or 5-1,3-thiazole ring with the general Formula (Ila), which can also be substituted. The invention also relates to said compound according to formula (I) for use in improving motivation and/or cognitive functions and/or for use in improving the reference memory in human individuals.

  本发明涉及具有一般式（I）的化合物的（S）-对映体；式（I）中，R1和R2相等或独立地为芳基、杂芳基、融合芳基、融合杂芳基、单取代或多取代芳基、单取代或多取代杂芳基、单取代或多取代融合和、单取代或多取代融合杂芳基；RTA为具有一般式（Ila）的2-1、3-或4-1、3-或5-1、3-硫唑环，该环也可以被取代。本发明还涉及根据式（I）的所述化合物在改善人体动机和/或认知功能和/或改善参考记忆方面的使用。
• (S)-ENANTIOMERIC FORM OF A HETEROCYCLIC COMPOUND HAVING MOTIVATION IMPROVING AND/OR REFERENCE MEMORY ENHANCING ACTIVITY
  申请人：Red Bull GmbH

  公开号：EP3553053A1

  公开（公告）日：2019-10-16

  The present invention relates to the (S)-enantiomer of the chemical compound having the general formula (I): wherein R1 and R2 are, equal or independently, aryl, heteroaryl, fused aryl, fused heteroaryl, mono or multi-substituted aryl, mono or multi-substituted heteroaryl, mono or multi-substituted fused aryl, mono or multi-substituted fused heteroaryl; and RTA is a 2-1,3-, or 4-1,3- or 5-1,3-thiazole ring with the general Formula (IIa), which can also be substituted. The invention also relates to said compound according to formula (I) for use in improving motivation and/or cognitive functions and/or for use in improving the reference memory in human individuals.

  本发明涉及具有通式（I）的化合物的（S）-对映体： 其中 R1 和 R2 相同或独立地为芳基、杂芳基、融合芳基、融合杂芳基、单取代或多取代芳基、单取代或多取代杂芳基、单取代或多取代融合芳基、单取代或多取代融合杂芳基；RTA 为通式（IIa）的 2-1，3-或 4-1，3-或 5-1，3-噻唑环，也可被取代。 本发明还涉及所述根据式（I）的化合物，用于改善人类的动机和/或认知功能和/或用于改善人类的参考记忆。
• THIAZOLE AND DIPHENYL SUBSTITUTED SULFOXIDES FOR USE IN IMPROVING COGNITION FUNCTIONS AND AGAINST ADDICTIONS TO SUBSTANCES.
  申请人：Red Bull GmbH

  公开号：EP3792252A1

  公开（公告）日：2021-03-17

  The present invention relates to a chemical compound having the general formula (I): wherein R1 is a phenyl group and R2 is a meta-substituted phenyl group; and RTA is a substituted or unsubstituted thiazole ring. The invention also relates to said compound according to formula (I), in particular in its diastereomerically pure or enriched form, for use in therapy, in particular for treating and/or preventing age-related cognitive decline. Further, the invention relates to said compound according to formula (I) for use in improving cognitive functions, in particular for use in improving the spatial learning capabilities in human individuals. And, invention also relates to said compound according to formula (I) for use in the treatment and/or prevention of alcohol addiction, nicotine addiction and/or drug addiction, in particular cocaine and/or metamphetamine addiction.

  本发明涉及一种具有通式（I）的化合物： 其中 R1 是苯基，R2 是元取代苯基；RTA 是取代或未取代的噻唑环。 本发明还涉及根据式（I）所述的化合物，特别是其非对映异构体纯度或富集形式，用于治疗，尤其是治疗和/或预防与年龄相关的认知功能衰退。此外，本发明还涉及根据式 (I) 所述的化合物，用于改善认知功能，特别是用于改善人类的空间学习能力。此外，本发明还涉及根据式（I）所述化合物用于治疗和/或预防酒精成瘾、尼古丁成瘾和/或药物成瘾，特别是可卡因和/或甲基苯丙胺成瘾。
• ((((3-HALOPHENYL)(PHENYL)METHYL)SULFINYL)METHYL)THIOPHENE COMPOUNDS AND DIASTEREOMERIC FORMS THEREOF FOR USE IN IMPROVING COGNITIVE FUNCTIONS
  申请人：Red Bull GmbH

  公开号：EP3929184A1

  公开（公告）日：2021-12-29

  The present invention relates to a chemical compound having the general formula (I): wherein R1 is a phenyl group or a substituted phenyl group, R2 is a meta-substituted phenyl group and RTA is a substituted or unsubstituted thiophene ring. The invention also relates to said compound according to formula (I), in particular in its diastereomerically pure or enriched form, for use in therapy, in particular for treating and/or preventing age-related cognitive decline. Further, the invention relates to said compound according to formula (I) for use in improving cognitive functions, in particular for use in improving the cognitive flexibility and/or learning capabilities and/or memory performance, and/or motivation in human individuals. And, invention also relates to said compound according to formula (I) for use in the treatment and/or prevention of alcohol addiction, nicotine addiction or drug addiction, in particular cocaine and/or metamphetamine addiction.

  本发明涉及一种具有通式（I）的化合物： 其中 R1 是苯基或取代苯基，R2 是元取代苯基，RTA 是取代或未取代的噻吩环。本发明还涉及根据式（I）所述的化合物，特别是其非对映异构体纯度或富集形式，用于治疗，尤其是治疗和/或预防与年龄相关的认知功能衰退。此外，本发明还涉及根据式（I）所述的用于改善认知功能的化合物，特别是用于改善人类的认知灵活性和/或学习能力和/或记忆能力和/或动机的化合物。此外，本发明还涉及根据式（I）所述化合物用于治疗和/或预防酒精成瘾、尼古丁成瘾或药物成瘾，特别是可卡因和/或甲基苯丙胺成瘾。