2-邻氯苯基四氢吡咯 | 129540-21-2

• 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-邻氯苯基四氢吡咯
• 中文别名: 2-(2-氯苯基)吡咯烷
• 英文名称: 2-(2-chlorophenyl)pyrrolidine
• CAS: 129540-21-2
• 化学式: C₁₀H₁₂ClN
• mdl: MFCD02089473
• 分子量: 181.665
• InChiKey: AFXDPDJNNABZGP-UHFFFAOYSA-N

物化性质

• 沸点：
  135-137 °C(Press: 16 Torr)
• 密度：
  1.129±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-邻氯苯基四氢吡咯 在 亚硝酸异戊酯 作用下， 以 四氢呋喃 为溶剂， 生成 2-(2-chloro-phenyl)-1-nitroso-pyrrolidine
  参考文献：
  名称：

  Cold Menthol Receptor Antagonists

  摘要：

  揭示了用于治疗各种疾病、综合症、症状和障碍的化合物、组合物和方法，包括疼痛。这些化合物由以下的化学式 I 表示：其中 A、B、L、Q、R1、R2 和 R3 在此处定义。

  公开号：

  US20100048589A1
• 作为产物：
  描述：

  邻氯苯甲酸乙酯 在 sodium tetrahydroborate 、 sodium hydride 作用下， 生成 2-邻氯苯基四氢吡咯
  参考文献：
  名称：

  Pyrroloisoquinoline antidepressants. 3. A focus on serotonin

  摘要：

  A collection of hexahydropyrroloisoquinoline derivatives (1-22), which represent a class of compounds that inhibit the neuronal uptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT), was investigated in vivo for serotonin-potentiating properties in the mouse head-twitch and rat serotonin syndrome assays. The p-methylthio compound 3b (McN-5652-Z) was found to possess exceptional activity in these assays, and the activity was attributable almost exclusively to the (+)-6S,10bR enantiomer. Ten closely related analogues were synthesized, tested, and compared among themselves and with some previously prepared compounds, both in vivo and in vitro. Several trans diastereomers exhibited strong inhibition of 5-HT uptake and substantial potentiation of 5-HT, while the cis diastereomers (3a, 4a, and 10a) tested were virtually devoid of such activity. Although 3b was only moderately selective in inhibiting the uptake of 5-HT vs NE, its 10-substituted analogues 4b, 7b-9b had improved 5-HT selectivity relative to NE, to the extent of 20-25 times (150-200 times relative to DA). Of these more selective compounds (in vitro), only 4b and 7b had substantial activity in vivo. Sulfoxide 11b appeared to function as a prodrug of 3b in vivo.

  DOI：

  10.1021/jm00172a018

文献信息

• [EN] TACHYKININ RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR TACHYKININE
  申请人：LILLY CO ELI

  公开号：WO2005000821A1

  公开（公告）日：2005-01-06

  The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.

  本发明涉及选择性NK-1受体拮抗剂的化学式(I)或其药用盐，用于治疗与过多的缓激肽相关的疾病。
• [EN] COMPOUNDS FOR THE MODULATION OF CYCLOPHILINS FUNCTION<br/>[FR] COMPOSÉS POUR LA MODULATION DE LA FONCTION DES CYCLOPHILINES
  申请人：UNIV COURT UNIV OF EDINBURGH

  公开号：WO2020043831A1

  公开（公告）日：2020-03-05

  The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof useful as inhibitors of Cyclophilins and modulators of cyclophilin-like proteins. The invention also relates to uses of said compounds in the treatment of various disorders. Formula (I), wherein: R1 and R2 are each independently is selected from the group consisting of -R, -haloalkyl, -hydroxyalkyl, -OR, -C(O)R, -CO2R, -C(O)N(R)2, -NRC(O)R, and - N(R)2; wherein R2 could also be a sulphide; each R is independently hydrogen, C 1-6 aliphatic, C3-10 aryl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered heterocylic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulphur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms selected from nitrogen, oxygen, or sulphur; R3 is Formual (Ia) selected from the group consisting of -OEt, and wherein R5 and R6 are independently selected from the group consisting of H, halide, methoxy, thiomethyl, morpholine and trifluoromethyl;R4 is selected from the group consisting of C1-6-alkyl-, and R4.1-CH2- wherein, R4.1 is C3-6-cycloalkyl-, a 5-6 membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, sulphur; optionally substituted with one R4.1.1 wherein, R4.1.1 is selected from -H, C1-4-alkyl, optionally substituted with one substituent selected from H2N(O)C- or EtO(O)C-;X is carbon or nitrogen; A is selected from the group consisting of 6 membered unsaturated ring, with 1-3 nitrogen atoms, which is optionally substituted by -NH2,and Formula (Ib), wherein ring B is a fused 5-10 membered saturated or partially unsaturated heterocyclic mono- bicyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen or sulphur, which is optionally substituted by -OH; and m is 1 or 2; and n is 1 or 2.

  本发明涉及式(I)的化合物或其药学上可接受的盐，其作为环肽酶的抑制剂和环肽酶样蛋白的调节剂。该发明还涉及所述化合物在治疗各种疾病中的用途。式(I)中：R1和R2各自独立地选自由-R、-卤代烷基、-羟基烷基、-OR、-C(O)R、-CO2R、-C(O)N(R)2、-NRC(O)R和-N(R)2等组成的群；其中R2也可以是硫化物；每个R独立地是氢、C1-6脂肪基、C3-10芳基、一个3-8成员饱和或部分不饱和的碳环、一个具有1-4个异原子（从氮、氧、硫中独立选择）的3-7成员杂环、或一个具有1-4个异原子（从氮、氧、硫中选择）的5-6成员单环杂芳基；R3是式(Ia)中选自-OEt的群，其中R5和R6各自独立地选自H、卤素、甲氧基、硫甲基、吗啉和三氟甲基的群；R4选自C1-6-烷基-和R4.1-CH2-，其中，R4.1是C3-6环烷基-、一个具有1-4个异原子（从氮、氧、硫中独立选择）的5-6成员杂环，可选地用一个R4.1.1取代，其中R4.1.1选自-H、C1-4-烷基，可选地用一个取代基（从H2N(O)C-或EtO(O)C-中选择）取代；X是碳或氮；A选自具有1-3个氮原子的6成员不饱和环，可选地用-NH2取代；和式(Ib)，其中环B是一个融合的5-10成员饱和或部分不饱和的杂环单双环，具有1-3个从氮、氧或硫中选择的异原子，可选地用-OH取代；m为1或2；n为1或2。
• A General Approach to Stereospecific Cross-Coupling Reactions of Nitrogen-Containing Stereocenters
  作者：Xinghua Ma、Haoran Zhao、Meruyert Binayeva、Glenn Ralph、Mohamed Diane、Shibin Zhao、Chao-Yuan Wang、Mark R. Biscoe

  DOI：10.1016/j.chempr.2020.02.002

  日期：2020.3

  A novel strategy employing cyclohexyl spectator ligands in Stille cross-coupling reactions has been developed as a general solution to the long-standing challenge of conducting stereospecific cross-coupling reactions at nitrogen-containing stereocenters. This method enables direct access to enantioenriched products that are difficult (or impossible) to obtain via alternative preparative methods. Selective

  作为在含氮立体中心进行立体定向交叉偶联反应的长期挑战的常规解决方案，已开发出在Stille交叉偶联反应中采用环己基旁观者配体的新策略。该方法使得能够直接获得难以（或不可能）通过替代制备方法获得的对映体富集的产品。在利用活化的和未活化的烷基单元之间的细微电子差异的反应条件下，可以实现单个仲烷基单元的选择性和可预测的转移。通过这种方法，在所有研究的实例中，对映体富集的α-甲锡烷基化的含氮立体中心都经历了Pd催化的芳构化和酰化反应，并具有极高的立体保真度。我们通过立体定向反应中使用α-苯乙烯基吡咯烷，氮杂环丁烷和开链（苄基和非苄基）亲核试剂来证明这一过程。该过程将有助于快速可靠地获得具有氮取代的立体中心的对映体富集的化合物，该化合物在从药物发现过程中出现的生物活性化合物中构成普遍存在的结构基序。
• Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships
  作者：Bruce E. Maryanoff、David F. McComsey、Joseph F. Gardocki、Richard P. Shank、Michael J. Costanzo、Samuel O. Nortey、Craig R. Schneider、Paulette E. Setler

  DOI：10.1021/jm00391a028

  日期：1987.8

  verified by enantiospecific synthesis starting with (+)-(R)-2-phenylpyrrolidine. Regarding the pendant phenyl ring, diverse substitution patterns were investigated. Those substitutions that were particularly unfavorable were 3',4',5'-trimethoxy (20b), 2',3',4',5',6'-pentafluoro (34b), 2'-trifluoromethyl (38b), 3',5'-bis(trifluoromethyl) (42b), 4'-n-butyl (44b), 2'-cyano (47b), 4'-methylsulfonyl (50b), and

  一系列吡咯并[2,1-a]异喹啉和相关化合物由于对丁苯那嗪诱导的上睑下垂和镇静作用以及对生物胺吸收的抑制作用而被检测为抗抑郁样活性。因此，我们已经鉴定出有史以来报道的一些最有效的TBZ诱导上睑下垂拮抗剂和一些最有效的多巴胺，去甲肾上腺素和血清素摄取抑制剂（在大鼠脑突触体中）。在这方面，特别值得注意的化合物分别是52b，29b，22b和48b。生物活性主要由反式异构体表现出来。而且，通过拆分四种化合物7b，24b，37b和48b，发现生物活性与（+）对映异构体亚组（在589 nm在MeOH中测得的盐）相关，对应于6S，10bR的绝对构型7b，37b，和48b，以及24b的6R，10bR配置。在（+）-24b X HBr上进行X射线测定，确定了其绝对构型；通过（+）-（R）-2-苯基吡咯烷开始的对映体特异性合成，验证了其他化合物的构型。关于侧苯环，研究了多种取代方式。那些特别不利的取代基是3'
• Stereocomplementary Synthesis of Pharmaceutically Relevant Chiral 2-Aryl-Substituted Pyrrolidines Using Imine Reductases
  作者：Yu-Hui Zhang、Fei-Fei Chen、Bo-Bo Li、Xin-Yi Zhou、Qi Chen、Jian-He Xu、Gao-Wei Zheng

  DOI：10.1021/acs.orglett.0c00802

  日期：2020.5.1

  sterically hindered 2-aryl-substituted pyrrolines. Using (R)-selective ScIR and (S)-selective SvIR, various chiral 2-aryl-substituted pyrrolidines with excellent enantioselectivity (>99% ee) were stereocomplementarily synthesized in good yield (60-80%), demonstrating the feasibility of IREDs for generating pharmaceutically relevant chiral 2-aryl-substituted pyrrolidine intermediates.

  探索天然存在的亚胺还原酶（IRED）的集合，确定了两个立体互补的IRED，它们对位阻2-芳基取代的吡咯啉的活性降低。使用（R）选择性ScIR和（S）选择性SvIR，以良好的收率（60-80％）立体互补合成了各种具有优异对映选择性（> 99％ee）的手性2-芳基取代的吡咯烷，证明了IRED的可行性用于产生药学上相关的手性2-芳基取代的吡咯烷中间体。