3-氯-4-碘苯腈 | 1261686-46-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氯-4-碘苯腈
• 英文名称: 3-chloro-4-iodobenzonitrile
• CAS: 1261686-46-7
• 化学式: C₇H₃ClIN
• 分子量: 263.465
• InChiKey: OUVGLBKTGXKVKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险类别：
  6.1
• 危险性防范说明：
  P501,P261,P270,P271,P264,P280,P337+P313,P305+P351+P338,P361+P364,P332+P313,P301+P310+P330,P302+P352+P312,P304+P340+P311,P403+P233,P405
• 危险品运输编号：
  3439
• 危险性描述：
  H301+H311+H331,H315,H319
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  3-氯-4-碘苯腈 在 四(三苯基膦)钯 、 sodium azide 、 三乙胺盐酸盐 、 sodium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1-[4-[2-chloro-4-(2H-tetrazol-5-yl)phenyl]phenyl]tetrazole
  参考文献：
  名称：

  Discovery of 5-(2-chloro-4′-(1H-imidazol-1-yl)-[1,1′-biphenyl]-4-yl)-1H-tetrazole as potent and orally efficacious S-nitrosoglutathione reductase (GSNOR) inhibitors for the potential treatment of COPD

  摘要：

  Endogenous nitrosothiols (SNOs) including S-nitrosoglutathione (GSNO) serve as reservoir for bioavailable nitric oxide (NO) and mediate NO-based signaling, inflammatory status and smooth muscle function in the lung. GSNOR inhibition increases pulmonary GSNO and induces bronchodilation while reducing inflammation in lung diseases. In this letter, design, synthesis and structure-activity relationships (SAR) of novel imidazole-biaryl-tetrazole based GSNOR inhibitors are described. Many potent inhibitors (30, 39, 41, 42, 44, 45 and 58) were identified with low nanomolar activity (IC(50)s: < 15 nM) along with adequate metabolic stability. Lead compounds 30 and 58 exhibited good exposure and oral bioavailability in mouse pharmacokinetic (PK) study. Compound 30 was selected for further profiling and revealed comparable mouse and rat GSNOR potency, high selectivity against alcohol dehydrogenase (ADH) and carbonyl reductase (CBR1) family of enzymes, low efflux ratio and permeability in PAMPA, a high permeability in CALU-3 assay, significantly low hERG activity and minimal off-target activity. Further, an in vivo efficacy of compound 30 is disclosed in cigarette smoke (CS) induced mouse model for COPD.

  DOI：

  10.1016/j.bmcl.2018.10.012
• 作为产物：
  描述：

  4-氨基-3-氯苯甲腈 在 碘 、 亚硝酸异戊酯 作用下， 以 苯 为溶剂， 生成 3-氯-4-碘苯腈
  参考文献：
  名称：

  影响光化学环脱氢氯化 (CDHC) 反应的参数

  摘要：

  研究了影响光化学环脱氯化氢（CDHC）反应结果的参数，包括溶剂的性质、浓度和氯化底物上官能团的存在。

  DOI：

  10.1002/cplu.202300677

文献信息

• [EN] ALKYNE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS<br/>[FR] COMPOSÉS DE TYPE ALCYNE EN TANT QU'INHIBITEURS DE LA S-NITROSOGLUTATHIONE RÉDUCTASE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2016055947A1

  公开（公告）日：2016-04-14

  Provided are compounds of formula (Ia) and pharmaceutically acceptable salts thereof, wherein A, B, R 1, R 2, m and n are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).

  提供的是式(Ia)的化合物及其药学上可接受的盐，其中A、B、R1、R2、m和n如本文所定义，这些化合物作为S-硝基谷胱甘肽还原酶(GSNOR)的抑制剂具有活性。这些化合物可以预防、抑制或抑制GSNOR的作用，因此在治疗GSNOR介导的疾病、疾病、综合征或病症方面具有用处，例如肺动脉高压、急性呼吸窘迫综合征(ARDS)、哮喘、支气管痉挛、咳嗽、肺炎、肺纤维化、间质性肺疾病、囊性纤维化和慢性阻塞性肺疾病(COPD)。
• 吡咯并吡唑类衍生物、其制备方法及其在医药上的应用
  申请人：上海美迪西生物医药股份有限公司

  公开号：CN112480119B

  公开（公告）日：2022-04-01

  本发明涉及吡咯并吡唑类衍生物、其制备方法及其在医药上的应用。具体的说，本发明涉及一类通式(I)所示的新的吡咯并吡唑类衍生物、其制备方法以及其本身或含有此类衍生物的药物组合物作为治疗剂，特别是作为胃酸分泌抑制剂和钾离子竞争性酸阻滞剂(P‑CABs)在生物医药中的用途。其中通式(I)中的各取代基(R1、R2、R3、R4、R5)和基团(X)与说明书中的定义相同。
• Synthesis of Ladder-Type π-Conjugated Heteroacenes via Palladium-Catalyzed Double N-Arylation and Intramolecular O-Arylation
  作者：Keiko Kawaguchi、Koji Nakano、Kyoko Nozaki

  DOI：10.1021/jo070427p

  日期：2007.7.1

  d‘]benzo[1,2-b:4,5-b‘]difurans, were effectively synthesized from the common intermediates, 2,5-bis(o-chloroaryl)hydroquinones. The key reactions are palladium-catalyzed double N-arylation of aniline and intramolecular O-arylation, which enable regioselective ring closure. In addition to the parent indolo[3,2-b]carbazole and dibenzo[d,d‘]benzo[1,2-b:4,5-b‘]difuran, their derivatives with an alkyl or cyano

  可以有效地合成含有吡咯或呋喃环，吲哚并[3,2- b ]咔唑和二苯并[ d，d ']苯并[1,2- b：4,5- b ']二呋喃的阶梯型杂并苯中间体2，5-双（邻氯芳基）氢醌。关键反应是钯催化的苯胺双N-芳基化和分子内的O-芳基化，从而实现区域选择性的闭环。除了母体吲哚[3,2- b ]咔唑和二苯并[ d，d ']苯并[1,2- b：4,5- b首先合成了′]二呋喃，其具有烷基或氰基的衍生物。光物理和电化学研究表明，与相应的烃并苯，并五苯相比，所获得的杂苯具有较低的HOMO能级和较大的带隙。对二苯并[ d，d ']苯并[1,2- b：4,5- b ']二呋喃的X射线分析表明，其以人字形包装。
• Design, syntheses and evaluations of novel indole derivatives as orally selective estrogen receptor degraders (SERD)
  作者：Jiaqiang Dong、Tie-lin Wang、Jianyu Lu、Charles Z. Ding、Lihong Hu、Guoping Hu、Huijun He、Xu Zeng、Xiaoting Li、Deheng Sun、Yingjie Zhu、Liang Shen、Qingyang Gu、Chi-chung Chan、Yuanfeng Xia、Jian Li、Shuhui Chen

  DOI：10.1016/j.bmcl.2020.127601

  日期：2020.11

  prolonged progression free survival of ER+ breast cancer patients. However, current SERD suffers from limited bioavailability, therefore is given as systemic injection. In this paper, we report herein a novel indole series compounds with nanomolar range ER degradation potencies and oral systemic exposures. Selected compounds suppressed tumor growth in vivo in ER+ MCF7 breast cancer CDX model via p.o. administration

  大多数雌激素受体（ER）+乳腺癌都依赖于ER信号通路来发展。SERD氟维司群的临床应用可有效降解ER，阻断其功能并延长ER +乳腺癌患者的无进展生存期。然而，目前的SERD具有有限的生物利用度，因此被认为是全身性注射。在本文中，我们在此报告了一种新型的吲哚系列化合物，具有纳摩尔范围的ER降解能力和口服全身暴露。选定的化合物通过口服给药在ER + MCF7乳腺癌CDX模型中抑制了体内肿瘤的生长。所有这些数据都支持对该类似物的进一步优化，以开发出临床前候选药物作为ER +乳腺癌治疗的口服SERD。
• [EN] IMIDAZOLE BIARYL COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS<br/>[FR] COMPOSÉS IMIDAZOLE BIARYLE EN TANT QU'INHIBITEURS DE LA S-NITROSOGLUTATHION RÉDUCTASE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2016046782A1

  公开（公告）日：2016-03-31

  The present disclosure is directed to compounds of formula (Ie) and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, m, n, X1, X2, X3 and X4 are as defined herein, which are active as inhibitors of S-Nitrosoglutathione reductase (GSNOR). These compounds prevent, inhibit, or suppress the action of GSNOR and are therefore useful in the treatment of GSNOR mediated diseases, disorders, syndromes or conditions such as, e.g., pulmonary hypertension, acute respiratory distress syndrome (ARDS), asthma, bronchospasm, cough, pneumonia, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis and chronic obstructive pulmonary disease (COPD).

  本公开涉及式(Ie)的化合物及其药用盐，其中A、B、R1、R2、m、n、X1、X2、X3和X4如本文所定义，这些化合物作为S-硝基谷胱甘肽还原酶(GSNOR)的抑制剂具有活性。这些化合物可以防止、抑制或抑制GSNOR的作用，因此在治疗GSNOR介导的疾病、紊乱、综合征或病况方面具有用处，例如肺动脉高压、急性呼吸窘迫综合征(ARDS)、哮喘、支气管痉挛、咳嗽、肺炎、肺纤维化、间质性肺疾病、囊性纤维化和慢性阻塞性肺病(COPD)。