4-(4-iodophenoxy)piperidine | 684249-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(4-iodophenoxy)piperidine
• CAS: 684249-45-4
• 化学式: C₁₁H₁₄INO
• 分子量: 303.143
• InChiKey: GTLXIPHKMBQJIK-UHFFFAOYSA-N

物化性质

• 沸点：
  352.4±37.0 °C(Predicted)
• 密度：
  1.562±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-iodophenoxy)piperidine 在 2-双环己基膦-2',6'-二甲氧基联苯 、 双(乙腈)氯化钯(II) 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 三乙胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(cyclopropyl(phenyl)methyl)-3-(4-((1-(2-(dimethylamino)-acetyl)piperidin-4-yl)oxy)phenyl)-1H-indazole-5-carboxamide
  参考文献：
  名称：

  The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors: 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents

  摘要：

  The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides are potent TTK inhibitors. However, they display modest ability to attenuate cancer cell growth; their physicochemical properties, and attendant pharmacokinetic parameters, are not drug-like. By eliminating the polar 3-sulfonamide group and grafting a heterocycle at the 4 position of the phenyl ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal structure and a refined binding model allowed for a structure guided approach. Systematic optimization resulted in novel TTK inhibitors, namely 3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10 nM, HCT116 GI(50) < 0.1 mu M), displayed low off-target activity (>500X), and microsomal stability (T-1/2 > 30 min). A subset was tested in rodent PK and mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral dosing, and was selected for preclinical evaluation.

  DOI：

  10.1021/jm501740a
• 作为产物：
  描述：

  N-Boc-4-羟基哌啶 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 4-(4-iodophenoxy)piperidine
  参考文献：
  名称：

  [EN] PLK-4 INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
  [FR] INHIBITEURS DE PLK4 ET MÉTHODE DE TRAITEMENT DU CANCER À L'AIDE DE CEUX-CI

  摘要：

  这项发明涉及一种由以下结构式（I）和（II）表示的化合物及其药学上可接受的盐：（结构式（I））；（结构式（IV））。由该结构式表示的化合物是激酶抑制剂，因此在此披露用于癌症治疗。结构式中变量的定义在此提供。

  公开号：

  WO2012048411A1

文献信息

• [EN] SUBSTITUTED PIPERAZINES, (1,4) DIASZEPINES, AND 2,5-DIAZABICYCLO (2.2.1) HEPTANES AS HISTAMINE H1 AND/OR H3 ANTAGONISTS OR HISTAMINE H3 REVERSE ANTAGONISTS<br/>[FR] PIPERAZINES, (1,4) DIAZEPINES, ET 2,5-DIAZABICYCLO (2.2.1) HEPTANES SUBSTITUES EN TANT QU'ANTAGONISTES DE L'HISTAMINE H1 ET/OU H3 OU ANTAGONISTES INVERSES DE L'HISTAMINE H3
  申请人：GLAXO GROUP LTD

  公开号：WO2004035556A1

  公开（公告）日：2004-04-29

  The present invention relates to novel piperazine and azepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurodegenerative disorders including Alzheimer's disease.

  本发明涉及具有药理活性的新型哌嗪和氮杂七元环衍生物，其制备方法，含有它们的组合物以及它们在治疗包括阿尔茨海默病在内的神经退行性疾病中的应用。
• [EN] MULTIPLE D2 A(NTA)GONISTS/H3 ANTAGONISTS FOR TREATMENT OF CNS-RELATED DISORDERS<br/>[FR] MULTIPLES A(NTA)GONISTES DE D2/ANTAGONISTES DE H3 POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS AU SNC
  申请人：AAPA B V

  公开号：WO2015069110A1

  公开（公告）日：2015-05-14

  The present invention relates to compounds compound according to Formula (III); and pharmaceutically acceptable salts, hydrates and solvates thereof. These compounds have D2receptor antagonist/(partial) agonist effects and H3antagonistic effects, pharmaceutical compositions thereof, and methods of using them for application in the prophylaxis or treatment of CNS disorders.

  本发明涉及按照式（III）的化合物；以及其药学上可接受的盐、水合物和溶剂合物。这些化合物具有D2受体拮抗/(部分)激动剂效应和H3拮抗效应，以及其药物组合物，以及将其用于预防或治疗中枢神经系统疾病的方法。
• [EN] NOVEL IMIDAZOLE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'IMIDAZOLE
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2018216822A1

  公开（公告）日：2018-11-29

  Provided are novel compounds represented by the following general formula [1] or pharmaceutically acceptable salts thereof, that inhibit LpxC, as well as pharmaceutical drugs comprising those compounds or pharmaceutically acceptable salts thereof, that exhibit antimicrobial activity against gram-negative bacteria including multi-drug resistant strains and that are useful in the treatment of bacterial infections.

  提供了由以下一般式[1]表示的新化合物或其药用盐，其抑制LpxC，以及包含这些化合物或其药用盐的药物，对革兰氏阴性细菌包括多药耐药菌株表现出抗微生物活性，并且在治疗细菌感染中有用。
• [EN] RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF<br/>[FR] INHIBITEURS DE RET, COMPOSITIONS PHARMACEUTIQUES ET UTILISATIONS ASSOCIÉES
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2020114494A1

  公开（公告）日：2020-06-11

  Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.

  本文提供了一种RET抑制剂，其药物组合物及用途。具体而言，提供了具有化学式（I）或其立体异构体、几何异构体、互变异构体、N-氧化物、溶剂合物、代谢物、药用可接受的盐或其前药的化合物。提供了包含该化合物的药物组合物，并提供了该化合物及其药物组合物的用途，用于制备药物，特别是用于治疗和预防与RET相关的疾病和症状，包括癌症、肠易激综合征以及与肠易激综合征相关的疼痛。
• [EN] 4- (4-(HETEROCYCLYLALKOXY}PHENYL)-1-(HETEROCYCLYL-CARBONYL)PIPERIDINE DERIVATIVES AND RELATED COMPOUNDS AS HISTAMINE H3 ANTAGONISTS FOR THE TREATMENT OF NEUROLOGICAL DISEASES SUCH AS ALZHEIMER'S<br/>[FR] DERIVES DE 4-(4-(HETEROCYCLYLALKOXY)PHENYL-1-(HETEROCYCLYL-CARBONYL)PIPERIDINE ET COMPOSES ASSOCIES SERVANT D'ANTAGONISTES D'HISTAMINE H3 DESTINES AU TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2004089373A1

  公开（公告）日：2004-10-21

  The present invention provides, in a first aspect, a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: R1 represents -C1-6 alkyl-O-C1-6 alkyl, -C3-8 cycloalkyl, aryl, heterocyclyl, heteroaryl and other groups; X represents a bond, O, CO, OCH2, CH2O or SO2; Z represents CO, CONR10 or SO2; R10 represents hydrogen, C1-6 alkyl, -C3-8 cycloalkyl, aryl, heterocyclyl, heteroaryl; A represents a single or a double bond; m and n independently represent 0, 1 or 2; R2 represents hydrogen, C1-6 alkyl or C1-6 alkoxy; R3 represents halogen, C1-6 alkyl, hydroxy, C1-6 alkoxy, cyano, amino, -COC1-6 alkyl, -SO2C1-6 alkyl or trifluoromethyl; R4 represents -(CH2)q-NR11R12 or a group of formula (i) wherein all the other substituents are as defined in claim 1. Compounds of formula (I) and their pharmaceutically acceptable salts have affinity for and are antagonists and/or inverse agonists of the histamine H3 receptor and are believed to be of potential use in the treatment of neurological diseases including Alzheimer's disease.

  本发明在第一方面提供了一个式(I)的化合物或其药学上可接受的盐，其中：R1代表-C1-6烷基-O-C1-6烷基，-C3-8环烷基，芳基，杂环烷基，杂芳基和其他基团；X代表键，O，CO，O ，CH2O或SO2；Z代表CO，CONR10或SO2；R10代表氢，C1-6烷基，-C3-8环烷基，芳基，杂环烷基，杂芳基；A代表单键或双键；m和n独立地代表0，1或2；R2代表氢，C1-6烷基或C1-6烷氧基；R3代表卤素，C1-6烷基，羟基，C1-6烷氧基，氰基，氨基，-COC1-6烷基，-SO2C1-6烷基或三氟甲基；R4代表-(CH2)q-NR11R12或一个式(i)的基团，其中所有其他取代基的定义如权利要求1所述。式(I)的化合物及其药学上可接受的盐具有亲和力，并且是组织胺H3受体的拮抗剂和/或逆向激动剂，被认为在治疗包括阿尔茨海默病在内的神经系统疾病中具有潜在用途。