4-[(thiophene-2-yl)carbonyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[(thiophene-2-yl)carbonyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester
• 英文别名: tert-butyl 4-(thiophene-2-carbonyl)piperidine-1-carboxylate；tert-butyl 4-(2-thienylcarbonyl)piperidine-1-carboxylate；4-(thiophene-2-carbonyl)-piperidine-1-carboxylic acid tert-butyl ester；4-[(thiophene-2-yl)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester
• 化学式: C₁₅H₂₁NO₃S
• 分子量: 295.403
• InChiKey: JILYOJKOXBLAKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  74.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(thiophene-2-yl)carbonyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester 在 盐酸 、 氢气 、 羟胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、310.27 kPa 条件下， 生成 2,4-dichloro-N-[[1-(1-methylimidazol-4-yl)sulfonylpiperidin-4-yl]-thiophen-2-ylmethyl]benzamide
  参考文献：
  名称：

  Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

  摘要：

  This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.011
• 作为产物：
  描述：

  1-Boc-4-[甲氧基(甲基)氨基甲酰]哌嗪 在 2-thienylmagnesium halide 作用下， 以 四氢呋喃 为溶剂， 生成 4-[(thiophene-2-yl)carbonyl]-1-piperidinecarboxylic acid,1,1-dimethylethyl ester
  参考文献：
  名称：

  Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: Development of a [3.3.0]-based series and other piperidine bioisosteres

  摘要：

  This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.011

文献信息

• Preparation of Unsymmetrical Ketones from Tosylhydrazones and Aromatic Aldehydes via Formyl C–H Bond Insertion
  作者：Daniel M. Allwood、David C. Blakemore、Steven V. Ley

  DOI：10.1021/ol5011714

  日期：2014.6.6

  Preparation of ketones by insertion of diazo compounds into the formyl C–H bond of an aldehyde is an attractive procedure, but use of structurally diverse diazo compounds is hampered by preparation and safety issues. A convenient procedure for the synthesis of unsymmetrical ketones from bench-stable tosylhydrazones and aryl aldehydes is reported. The procedure can be performed in one pot from the parent

  通过将重氮化合物插入醛的甲酰基C–H键来制备酮是一种有吸引力的方法，但是结构多样化的重氮化合物的使用受到制备和安全性问题的阻碍。报道了一种由台式稳定的甲苯磺酰hydr和芳基醛合成不对称酮的简便方法。该过程可以在一个母体羰基化合物的罐中进行，只需要一种碱，而无需额外的促进剂。
• Benzoyl-piperidine derivatives as dual modulators of the 5-HT2A and D3 receptors
  申请人：Gobbi Luca

  公开号：US20070197531A1

  公开（公告）日：2007-08-23

  The present invention relates to compounds of the general formula as dual modulators of the 5-HT 2a and D 3 receptors useful against CNS disorders, wherein A, R 1 , R 2 , n, p, q and r are as defined in the specification.

  本发明涉及一般公式的化合物，作为5-HT2a和D3受体的双重调节剂，用于对抗中枢神经系统疾病，其中A、R1、R2、n、p、q和r的定义如规范中所述。
• Novel heterocyclic urea derivatives and their use as dopamine D3 receptor ligands
  申请人：——

  公开号：US20030229066A1

  公开（公告）日：2003-12-11

  The invention relates to heterocyclic substituted urea derivatives that display selective binding to dopamine D 3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D 3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D 3 receptors.

  该发明涉及对多巴胺D3受体显示选择性结合的杂环取代脲衍生物。另一方面，该发明涉及一种用于治疗中枢神经系统疾病的方法，该疾病与多巴胺D3受体活性有关，患者需要接受此类治疗，包括向受试者施用所述化合物的治疗有效量以缓解此类疾病。可以用这些化合物治疗的中枢神经系统疾病包括精神病性障碍、物质依赖、物质滥用、运动障碍（如帕金森病、帕金森综合症、神经阻滞引起的迟发性运动障碍、吉尔·德·拉·图雷特综合征和亨廷顿病）、痴呆、焦虑障碍、睡眠障碍、昼夜节律障碍和情绪障碍。该发明还涉及所述化合物的制备过程以及将其作为多巴胺D3受体成像剂的方法。
• Design and synthesis of a novel series of orally active, selective somatostatin receptor 2 agonists for the treatment of type 2 diabetes
  作者：Yoshihiro Banno、Shigekazu Sasaki、Makoto Kamata、Jun Kunitomo、Yasufumi Miyamoto、Hidenori Abe、Naohiro Taya、Satoru Oi、Masanori Watanabe、Tomoko Urushibara、Masatoshi Hazama、Shin-ichi Niwa、Saku Miyamoto、Akira Horinouchi、Ken-ichi Kuroshima、Nobuyuki Amano、Shin-ichi Matsumoto、Shinichiro Matsunaga

  DOI：10.1016/j.bmc.2017.09.031

  日期：2017.11

  The discovery of a novel series of β-methyltryptophan (β MeTrp) derivatives as selective and orally active non-peptide somatostatin receptor 2 (SSTR2) agonists for the treatment of Type 2 diabetes is described. In our previous research, Compound A, β-MeTrp derivative with highly potent and selective SSTR2 agonistic activity IC50 (SSTR2/SSTR5) = 0.3/>100 (nM), was identified as a drug candidate for

  描述了发现一系列新型的β-甲基色氨酸（βMeTrp）衍生物作为选择性和口服活性非肽生长抑素受体2（SSTR2）激动剂，用于治疗2型糖尿病。在我们之前的研究中，化合物A，β-MeTrp衍生物具有强效的选择性SSTR2激动活性IC 50（SSTR2 / SSTR5）= 0.3 /> 100（nM）被确定为治疗2型糖尿病的候选药物，该药物可显着降低Wistar脂肪大鼠口服中的血浆葡萄糖水平。然而，由于在大鼠的毒理学研究中观察到AUC和磷脂病（PLsis）的严重增加，因此根据在HepG2中磷脂积累的基础上评估的体外PLsis潜力，对后续化合物进行了研究以避免PLsis的风险暴露于化合物的细胞。 已经发现将羰基引入化合物A和B的哌啶和哌嗪或苯胺部分上显着降低了体外PLsis电位。化合物的进一步修饰及其评估导致发现具有较低体外PLsis电位的化合物3k，其在SD大鼠中表现出低血糖诱导的胰高血糖素分泌降低的作用（ED
• Piperidinyl thiacyclic derivatives
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05371093A1

  公开（公告）日：1994-12-06

  Piperidinyl thiacyclic derivatives ##STR1## wherein X, Y, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are defined in the specification. useful in the treatment of allergic diseases and diseases responding to antagonism of 5HT.sub.2 receptors, pharmaceutical compositions and a methods of treatment using these compounds.

  吡啶基硫代环丙衍生物，其中X、Y、R₁、R₂、R₃和R₄在规范中有定义。在过敏性疾病和对5HT₂受体拮抗有反应的疾病的治疗中有用，以及使用这些化合物的制药组合物和治疗方法。