N-(3-(benzo[d]thiazol-2-yl)-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide | 524708-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: N-(3-(benzo[d]thiazol-2-yl)-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide
• 英文别名: N-(3-Benzo[d]thiazol-2-yl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)-acetamide；N-[3-(1,3-benzothiazol-2-yl)-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl]acetamide；N-[3-(1,3-benzothiazol-2-yl)-6-benzyl-5,7-dihydro-4H-thieno[2,3-c]pyridin-2-yl]acetamide
• CAS: 524708-01-8
• 化学式: C₂₃H₂₁N₃OS₂
• 分子量: 419.571
• InChiKey: VBKOTDOZGCZROG-UHFFFAOYSA-N

物化性质

• 密度：
  1.352±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 2-amino-3-(benzo[d]thiazol-2-yl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate 在 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-(3-(benzo[d]thiazol-2-yl)-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Structure–Activity Relationships of a Novel Class of Apurinic/Apyrimidinic Endonuclease 1 Inhibitors

  摘要：

  APE1 is an essential protein that operates in the base excision repair (BER) pathway and is responsible for >= 95% of the total apurinic/apyrimidinic (AP) endonuclease activity in human cells. BER is a major pathway that copes with DNA damage induced by several anticancer agents, including ionizing radiation and temozolomide. Overexpression of APEI and enhanced AP endonuclease activity have been linked to increased resistance of tumor cells to treatment with monofunctional alkylators, implicating inhibition of APEI as a valid strategy for cancer therapy. We report herein the results of a focused medicinal chemistry effort around a novel APEI inhibitor, N-(3-(benzo[d]thiazol-2-yl)-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide (3). Compound 3 and related analogues exhibit single-digit micromolar activity against the purified APE1 enzyme and comparable activity in HeLa whole cell extract assays and potentiate the cytotoxicity of the alkylating agents methylmethane sulfonate and temozolomide. Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice.

  DOI：

  10.1021/jm201537d

文献信息

• HETEROCYCLIC INHIBITORS OF AN Hh-SIGNAL CASCADE, MEDICINAL COMPOSITIONS BASED THEREON AND METHODS FOR TREATING DISEASES CAUSED BY THE ABERRANT ACTIVITY OF AN Hh-SIGNAL SYSTEM
  申请人：Ivaschenko Andrey Alexandrovich

  公开号：US20110053915A1

  公开（公告）日：2011-03-03

  The invention relates to novel heterocyclic compounds and to the use thereof, to pharmaceutical compositions containing said chemical compounds as an active ingredient and to the use thereof for producing medicinal preparations for the human being and warm-blood animals for treating diseases caused by the aberrant activity of an Hedgehog (Hh)-signal system, in particular oncological diseases. The invention also relates to the use of the above-mentioned compounds in the form of ‘molecular pharmacological tools’ for examining (in vitro and in vivo) the biochemical features of the Hh-signal system, in particular, the interaction of Hh protein and transmembrane proteins, namely, suppressor Patched (Ptc) and protooncogenic proteins. The eight groups of the claimed compounds comprise the derivatives of 2,6-dihydro-7H-pyrazolo[3,4-d]pyridazine-7-one and 1,4-dihydropyrazolo[3,4-b][1,4]thiazine-5-one; N-acidylated 4-imidazo[1,2-a]pyrimidine-2-il-anilines; ([4H-thino[3,2-b]pyrrol-5-il) carbonyl]piperidine-4-carbonic acid amides; 2-(4carbomoilpyperidine-1-il)-isonicotinic acid amides; N-sylphonyl-1,2,3,4-tetrahydroquinoline-6-carbonic acid amides; and pyridine 2-amino-4,5,6,7-tetrahydrothieno[2,3-c] N-acidylated 3-azole derivatives.

  该发明涉及新颖的杂环化合物及其用途，包括含有该化合物作为活性成分的药物组合物，以及用于制备用于治疗由Hedgehog（Hh）信号系统异常活性引起的人类和温血动物疾病的药物制剂。该发明还涉及上述化合物的使用形式为“分子药理学工具”，用于检查Hh信号系统的生化特征（体外和体内），特别是Hh蛋白与跨膜蛋白之间的相互作用，即抑制剂Patched（Ptc）和原癌基因蛋白。所述化合物的八个类别包括2,6-二氢-7H-吡唑并[3,4-d]吡啶嗪-7-酮和1,4-二氢吡唑并[3,4-b][1,4]噻嗪-5-酮的衍生物；N-酰化的4-咪唑并[1,2-a]嘧啶-2-基-苯胺；([4H-噻吩[3,2-b]吡咯-5-基)羰基]哌啶-4-羧酸酰胺；2-(4-羧甲基哌啶-1-基)-异尼古丁酸酰胺；N-磺酰基-1,2,3,4-四氢喹啉-6-羧酸酰胺；以及吡啶2-氨基-4,5,6,7-四氢噻吩[2,3-c] N-酰化的3-唑衍生物。
• [EN] INHIBITORS OF HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE 1<br/>[FR] INHIBITEURS D'ENDONUCLÉASE APURINIQUE/APYRIMIDIQUE 1
  申请人：US HEALTH

  公开号：WO2012148889A1

  公开（公告）日：2012-11-01

  Disclosed are inhibitors of human APE1, for example, of formula (I), wherein A, B, X, R2, and R3 are as defined herein, that are useful in treating an APE1 mediated disease or disorder, e.g., cancer. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of treating cancer in a mammal and a method of potentiating treatment of cancer.

  本文披露了人类APE1的抑制剂，例如公式(I)所示，其中A、B、X、R2和R3的定义如本文所述，这些抑制剂对治疗APE1介导的疾病或紊乱，如癌症，是有用的。还披露了一种包含药学适宜载体和本发明中至少一种化合物的组合物，一种治疗哺乳动物癌症的方法以及一种增强癌症治疗的方法。
• COMPOUNDS FOR TREATING PROTEIN FOLDING DISORDERS
  申请人：Tait Bradley

  公开号：US20130072473A1

  公开（公告）日：2013-03-21

  The present invention is directed to compounds of Formulae (I), (IIa-IIh), (IIIa-IIIe), (IVa-IVc), (Va-V1), (VIa-VII), (VII), (VIII) and (IX), pharmaceutical compositions thereof and methods of use thereof in the treatment of conditions associated with a dysfunction in proteostasis.

  本发明涉及式(I)、(IIa-IIh)、(IIIa-IIIe)、(IVa-IVc)、(Va-V1)、(VIa-VII)、(VII)、(VIII)和(IX)化合物，以及其制备的药物组合物和治疗与蛋白质稳态失调相关疾病的方法。
• US8486945B2
  申请人：——

  公开号：US8486945B2

  公开（公告）日：2013-07-16
• [EN] HETEROCYCLIC INHIBITORS OF AN Hh-SIGNAL CASCADE, MEDICINAL COMPOSITIONS BASED THEREON AND METHODS FOR TREATING DISEASES CAUSED BY THE ABERRANT ACTIVITY OF AN Hh-SIGNAL SYSTEM<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES D'UNE CASCADE DE SIGNAUX Hh, COMPOSITIONS MÉDICINALES À BASE DE CES INHIBITEURS ET MÉTHODES DE TRAITEMENT DE MALADIES PROVOQUÉES PAR L'ACTIVITÉ ABERRANTE DU SYSTÈME DE SIGNALISATION Hh
  申请人：ALLA CHEM LLC

  公开号：WO2009077956A2

  公开（公告）日：2009-06-25

  Настоящее изобретение относится к новым гетероциклическим соединениям и их применению, а также к фармацевтическим композициям, включающим данные химические соединения в качестве активного ингредиента, и использованию их при изготовлении лекарственных препаратов для людей и теплокровных животных, применяемых для лечения болезней, связанных с абберантной активностью Неdgеhоg (Hh) сигнальной системы, в частности, онкологических заболеваний. Изобретение относится также к применению данных соединений в качестве «мoлeкyляpныx фармакологических инструментов) для исследований (in vitrо и in vivо) биохимических особенностей Hh сигнальной системы, в частности, взаимодействия Hh протеина и трансмембранных белков: супрессорного Раtсhеd (Рtс) и протоонкогенного Smооthеnеd (Smо). Восемь групп заявляемых соединений включают в себя производные 2,6-дигидpo- 7H-пиpaзoлo[3,4-d]пиpидaзин-7-oнa и 1,4-дигидpoпиpaзoлo[3,4-b][1,4]тиaзин-5-oнa; N- ацилированные 4-имидaзo[l,2-a]пиpидин-2-ил- и 4-имидaзo[l,2-a]пиpимидин-2-ил- анилины; амиды [(4H-тиeнo[3,2-b]пиppoл-5-ил)кapбoнил]пипepидин-4-кapбo новой кислоты; амиды 2- (4-кapбaмoилпипepидин-1-ил)-изo никотиновой кислоты; амиды N- cyльфoнил-1,2,3,4-тeтpaгидpoxинoлин-6-кapбoнoвoй кислоты; а также N-ацилированные 3-aзoлильныe производные 2-aминo-4,5,6,7-тeтpaгидpoтиeнo[2,3-c]пиpидинa.