2-羟基-3-(2-苯基-2-氧代)乙基-1,4-萘醌 | 59378-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 2-羟基-3-(2-苯基-2-氧代)乙基-1,4-萘醌
• 英文名称: N-(tert-butoxycarbonyl)pyrrolidine-2-carboxaldehyde
• 英文别名: tert-butyl 2-formylpyrrolidine-1-carboxylate；2-formylpyrrolidine-1-carboxylic acid tert-butyl ester；N-Boc-2-formylpyrrolidine；1-Boc-2-Formylpyrrolidine
• CAS: 59378-82-4
• 化学式: C₁₀H₁₇NO₃
• mdl: MFCD03790896
• 分子量: 199.25
• InChiKey: YDBPZCVWPFMBDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  14.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  2.0

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-tert-butoxycarbonyl-proline	15761-39-4	C10H17NO4	215.249
  2-羟甲基吡咯烷-1-羧酸丁酯	N-Boc-prolinol	170491-63-1	C10H19NO3	201.266
  Boc-D-脯氨醇	1-(tert-butoxycarbonyl)prolin-2R-ol	83435-58-9	C10H19NO3	201.266
  Boc-L-脯氨酸甲酯	(S)-N-(tert-butoxycarbonyl)proline methyl ester	59936-29-7	C11H19NO4	229.276
  1-Boc-2-吡咯烷甲酸甲酯	(+/-)-N-tert-butoxycarbonylproline methyl ester	145681-01-2	C11H19NO4	229.276
  1-Boc-四氢吡咯	tert-butyl pyrrolidine-1-carboxylate	86953-79-9	C9H17NO2	171.239
  1-Boc-N-甲基-N-甲氧基-2-吡咯烷甲酰胺	(S)-2-[(methoxymethylamino)carbonyl]-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester	334872-14-9	C12H22N2O4	258.318

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	tert-butyl (2R)-2-(2-oxoethyl)pyrrolidine-1-carboxylate	916263-26-8	C11H19NO3	213.277
  2-羟甲基吡咯烷-1-羧酸丁酯	N-Boc-prolinol	170491-63-1	C10H19NO3	201.266
  ——	2-(2-cyano-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	1161438-33-0	C12H20N2O2	224.303
  (R)-叔丁基 2-(2-羟基乙基)吡咯烷-1-羧酸	tert-butyl (2R)-2-(2-hydroxyethyl)pyrrolidine-1-carboxylate	132482-06-5	C11H21NO3	215.293
  N-boc-2-乙烯基吡咯烷	tert-butyl 2-vinylpyrrolidine-1-carboxylate	176324-60-0	C11H19NO2	197.277
  ——	1,1-dimethylethyl (2R)-2-ethenyl-1-pyrrolidinecarboxylate	340129-94-4	C11H19NO2	197.277
  2-乙炔-1-吡咯烷羧酸-1,1-二甲基乙酯	tert-butyl 2-ethynylpyrrolidine-1-carboxylate	316141-37-4	C11H17NO2	195.261
  2-(1-羟乙基)吡咯烷-1-羧酸叔丁酯	tert-butyl 2-(1-hydroxyethyl)pyrrolidine-1-carboxylate	916145-68-1	C11H21NO3	215.293
  ——	N-Boc-L-prolinal oxime	——	C10H18N2O3	214.265
  ——	N-(N-t-butoxycarbonyl-2(S)-pyrrolidinylmethyl)glycine methyl ester	124072-83-9	C13H24N2O4	272.345

反应信息

• 作为反应物：
  描述：

  2-羟基-3-(2-苯基-2-氧代)乙基-1,4-萘醌 在 四(三苯基膦)钯 、 碳酸氢钠 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 49.0h， 生成 拉维达韦
  参考文献：
  名称：

  Ledipasvir (GS-5885) 的发现：一种用于治疗丙型肝炎病毒感染的强效、每日一次的口服 NS5A 抑制剂

  摘要：

  发现了一类具有不对称苯并咪唑-二氟芴-咪唑核心和远端[2.2.1]氮杂双环系统的新型高效NS5A抑制剂。抗病毒效力和药代动力学的优化导致鉴定出39 种（ledipasvir，GS-5885）。化合物39 (GT1a 复制子 EC 50 = 31 pM) 在健康志愿者中具有延长的血浆半衰期 37-45 小时，并且在口服剂量为 3 mg 或更大且每天一次的单一疗法中产生快速 > 3 log 病毒载量降低在基因型 1a HCV 感染患者中给药。39已被证明是安全有效的，当与具有互补机制的直接作用抗病毒药物联合使用时，SVR12 率高达 100%。

  DOI：

  10.1021/jm401499g
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 2-羟基-3-(2-苯基-2-氧代)乙基-1,4-萘醌
  参考文献：
  名称：

  Dihydropyridinone approach to manzamines: An expedient construction of the tetracyclic core of manzamine A

  摘要：

  A construction of the central tetracyclic core (19) of manzamine A (1) was successfully achieved by a highly efficient Diels-Alder reaction of the suitably protected dihydropyridinones (5) and Danishefsky's diene as a key strategy. Expedient conversion of the D-A product (7) to the precursor (15) was followed by the azocine lactam ring closure to furnish the titled core.

  DOI：

  10.1016/0040-4039(93)88081-s

文献信息

• N-acylpyrrolidin-2-ylalkylbenzamidine derivatives as inhibitors of factor Xa
  申请人：——

  公开号：US20030092698A1

  公开（公告）日：2003-05-15

  This invention is directed to N-acylpyrrolidin-2-ylalkylbenzamidine derivatives which useful for inhibiting the activity of Factor Xa, by contacting said derivatives with a composition containing Factor Xa. The present invention is also directed to compositions containing said derivatives, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.

  这项发明涉及N-酰基吡咯啉-2-基烷基苯甲酰胺衍生物，用于通过将这些衍生物与含有凝血因子Xa的组合物接触来抑制凝血因子Xa的活性。本发明还涉及含有这些衍生物的组合物、它们的制备方法，以及它们的用途，例如用于抑制凝血酶的形成或用于治疗患有与生理上有害的凝血酶过量相关的疾病状态的患者。
• [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2012169649A1

  公开（公告）日：2012-12-13

  The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]
• [EN] PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE PROTÉINE TYROSINE PHOSPHATASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CALICO LIFE SCIENCES LLC

  公开号：WO2020186199A1

  公开（公告）日：2020-09-17

  Provided herein are compounds, compositions, and methods useful for inhibiting protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases, disorders and conditions favorably responsive to PTPN 1 or PTPN2 inhibitor treatment, e.g., a cancer or a metabolic disease.

  本文提供了用于抑制蛋白酪氨酸磷酸酶的化合物、组合物和方法，例如蛋白酪氨酸磷酸酶非受体型2（PTPN2）和/或蛋白酪氨酸磷酸酶非受体型1（PTPN1），以及用于治疗对PTPN1或PTPN2抑制剂治疗有良好反应的相关疾病、紊乱和状况的方法，例如癌症或代谢性疾病。
• [EN] SUBSTITUTED BENZAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011076678A1

  公开（公告）日：2011-06-30

  The invention relates to compounds of formula I wherein R is hydrogen or lower alkyl; R1 is -(CH2)n-(O)o-heterocycloalkyl or -C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by -(CH2)p-aryl; n is 0, 1 or 2; o is 0 or 1; p is 0, 1 or 2; R2 is CF3, cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl, or is aryl or heteroaryl, wherein the aromatic rings are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF3, OCF3, OCH2CF3, OCH2-cycloalkyl, OCH2C(CH2OH)(CH2C1)(CH3), S-lower alkyl, lower alkoxy, CH2-lower alkoxy, lower alkinyl or cyano, or by-C(O)-phenyl, -O-phenyl, -O- CH2-phenyl, phenyl or -CH2-phenyl, and wherein the phenyl rings may optionally be substituted by halogen, -C(O)-lower alkyl, -C(O)OH or -C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH2-oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; X is a bond, -NR'-, -CH2NH-, -CHR''-, -(CHR'')q-O-, -O-(CHR'')q- or -(CH2)2-; Y is a bond or -CH2- R' is hydrogen or lower alkyl, R'' is hydrogen, lower alkyl, CF3, lower alkoxy, q is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinsons disease, neurodegenerative disorders such as Alzheimers disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  该发明涉及以下式I的化合物，其中R是氢或较低的烷基；R1是-(CH2)n-(O)o-杂环烷基或-C(O)-杂环烷基，其中杂环烷基基团可选择地被较低的烷基，羟基，卤素或-(CH2)p-芳基取代；n为0、1或2；o为0或1；p为0、1或2；R2为CF3，环烷基，可选择地被较低的烷氧基或卤素取代，或为茚-2-基，或为杂环烷基，可选择地被杂芳基取代，或为芳基或杂芳基，其中芳香环可选择地被来自较低的烷基，卤素，杂芳基，羟基，CF3，OCF3，OCH2CF3，OCH2-环烷基，OCH2C(CH2OH)(CH2C1)(CH3)，S-较低的烷基，较低的烷氧基，CH2-较低的烷氧基，较低的炔基或氰基，或-C(O)-苯基，-O-苯基，-O-CH2-苯基，苯基或-CH2-苯基选择的一个或两个取代基取代，其中苯环可选择地被卤素，-C(O)-较低的烷基，-C(O)OH或-C(O)O-较低的烷基取代，或芳香环可选择地被杂环烷基，OCH2-氧杂环戊烷-3-基或O-四氢吡喃-4-基，可选择地被较低的烷基取代；X为键，-NR'-，-CH2NH-，-CHR''-，-(CHR'')q-O-，-O-(CHR'')q-或-(CH2)2-；Y为键或-CH2-；R'为氢或较低的烷基，R''为氢，较低的烷基，CF3，较低的烷氧基，q为0、1、2或3；或其药学上适宜的酸盐。现已发现，该式I的化合物对痕量胺相关受体（TAARs）具有良好的亲和力，特别是对于TAAR1。这些化合物可用于治疗抑郁症，焦虑症，躁郁症，注意力缺陷多动障碍（ADHD），与压力有关的疾病，如精神分裂症，帕金森病等神经疾病，阿尔茨海默病等神经退行性疾病，癫痫，偏头痛，高血压，物质滥用和代谢性疾病，如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和吸收异常，体温稳态异常，睡眠和昼夜节律异常，以及心血管疾病。
• Anti-Viral Compounds
  申请人：DeGoey David A.

  公开号：US20100317568A1

  公开（公告）日：2010-12-16

  Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

  描述了一种有效抑制丙型肝炎病毒（“HCV”）复制的化合物。本发明还涉及制备这种化合物的方法、包含这种化合物的组合物，以及使用这种化合物治疗HCV感染的方法。

表征谱图