1-benzyloxy-4-(3-phthalimidopropoxy)benzene | 90816-84-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-benzyloxy-4-(3-phthalimidopropoxy)benzene
• 英文别名: N-<3-<4-(benzyloxy)phenoxy>propyl>phthalimide；N-[3-(4-benzyloxyphenoxy)propyl]phthalimide；2-{3-[4-(phenylmethoxy)phenoxy]propyl}isoindoline-1,3-dione；2-[3-(4-benzyloxy-phenoxy)-propyl]-isoindole-1,3-dione；2-[3-(4-phenylmethoxyphenoxy)propyl]isoindole-1,3-dione
• CAS: 90816-84-5
• 化学式: C₂₄H₂₁NO₄
• 分子量: 387.435
• InChiKey: CSIVGYXCVZLMHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyloxy-4-(3-phthalimidopropoxy)benzene 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以76%的产率得到N-<3-(4-hydroxyphenoxy)propyl>phthalimide
  参考文献：
  名称：

  二氢蝶呤合酶的亚硝基异胞嘧啶抑制剂的半乳糖苷衍生物：合成与生物学评价

  摘要：

  二氢蝶呤合酶抑制剂6-（3-（4-羟基苯氧基）丙基氨基）-5-亚硝基异胞嘧啶（2）的O-β- D-半乳糖基衍生物3的合成是通过N-（3-（4-羟基苯氧基）丙基）邻苯二甲酰亚胺（4）与2,3,4,6-四-O-乙酰基-α-D-吡喃半乳糖基溴化物，然后用肼然后用甲醇氨完全解封所得的β-糖苷9，得到胺10，然后将10与6-甲硫基-5-亚硝基异胞嘧啶缩合（11）。糖苷3以中等效力抑制合成酶（I50 = 11μM），但没有表现出抗菌活性。

  DOI：

  10.1002/jhet.5570230265
• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 、 4-苄氧基苯酚 在 sodium hydride 作用下， 生成 1-benzyloxy-4-(3-phthalimidopropoxy)benzene
  参考文献：
  名称：

  二氢蝶呤合酶的抑制剂：6-[[[3-（芳氧基）丙基]氨基] -5-亚硝基异胞嘧啶的侧链芳环中的取代基作用以及桥连的5-亚硝基异胞嘧啶-对氨基苯甲酸类似物的合成和抑制作用。

  摘要：

  我们先前曾报道6-（甲基氨基）-5-亚硝基异胞嘧啶（5）是大肠杆菌二氢蝶呤合酶的有效抑制剂（I50 = 1.6 microM）。注意到大于甲基的6-氨基取代基不利于结合，尽管可以通过在某些6-烷基氨基取代基的末端连接的苯环的辅助辅助结合作用来克服不利的空间效应。我们选择6-[[[3-（芳氧基）丙基]氨基] -5-亚硝基异胞嘧啶结构作为母体系统，并探讨了芳香族取代基对合酶抑制的影响。芳基取代的性质会影响结合，如15种芳基类似物的30倍抑制力范围所示（I50值= 0.6-18 microM），尽管合酶抑制与芳基取代基的电子或疏水特性之间没有明显的相关性。为了探索这些抑制剂的芳环可能与底物对氨基苯甲酸（PABA）的合酶结合位点相互作用的可能性，合成了三种化合物，其中PABA类似物通过与氨基连接而桥接到亚硝基异胞嘧啶部分在异胞嘧啶的C-6上。与（芳氧基）丙基系列的其他成员相比，桥接的类似物显着抑制了合酶（I50值=

  DOI：

  10.1021/jm00155a014

文献信息

• Therapeutic amines
  申请人：Zeneca Limited

  公开号：US05866611A1

  公开（公告）日：1999-02-02

  Compounds of formula I, and their pharmaceutically acceptable salts, ##STR1## in which R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl or alkenyl; or NR.sup.1 R.sup.2 is a heterocyclic group; A is trimethylene optionally substituted by alkyl and the phenyl ring is optionally substituted by substituents such as halogeno, alkenyl, amino, cyano, ureido, alkyl, carbamoylalkyl, alkanoylamino, alkoxycarbonyl, N-alkyl-alkanoylamino, alkanoyl and amines thereof; are inhibitors of squalene synthese and hence useful in treating diseases in which a lowering of cholesterol is desirable. As well as the use of these compounds in medicine, novel compounds, processes for their preparation and pharmaceutical compositions are also referred to.

  式I的化合物及其药学上可接受的盐，其中R.sup.1和R.sup.2分别为氢、烷基、环烷基、环烷基烷基、苯基烷基或烯基；或NR.sup.1 R.sup.2是杂环基团；A是可选择地由烷基取代的三亚甲基，苯环可选择地由卤素、烯基、氨基、氰基、脲基、烷基、碳酰胺基烷基、烷酰氨基、烷氧羰基、N-烷基-烷酰氨基、烷酰基及其胺基取代基取代；这些化合物是角鲨烯合成酶的抑制剂，因此在治疗降低胆固醇的疾病中有用。除了这些化合物在医学上的用途外，还提到了新颖的化合物、其制备方法和药物组合物。
• Substituted (10H-phenothiazin-10-L)-propyl-1-piperazines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04471116A1

  公开（公告）日：1984-09-11

  Substituted (10H-phenothiazin-10-yl)propyl-1-piperazines of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, A, X, m, n and s are as hereinafter set forth, are described. The compounds of formula I, which contain a piperazine moiety combined by an ether linkage to different phenolic moieties, are useful as orally active long lasting antipsychotic agents.

  描述了以下结构的化合物：##STR1## 其中 R.sub.1、R.sub.2、R.sub.3、A、X、m、n 和 s 如下所述。公式I的化合物包含一种哌嗪基团，通过醚键结合到不同的酚基团，可用作口服长效抗精神病药物。
• Compounds with mixed pde-inhibitory and beta-adrenergic antagonist or partial agonist activity for treatment of heart failure
  申请人：Hamilton S. Gregory

  公开号：US20070060748A1

  公开（公告）日：2007-03-15

  This invention provides compounds that possess inhibitory activity against β-adrenergic receptors and phosphodiesterase PDE, including phosphodiesterase 3 (PDE3). This invention further provides pharmaceutical compositions comprising such compounds; methods of using such compounds for treating cardiovascular disease, stroke, epilepsy, ophthalmic disorder or migraine; and methods of preparing pharmaceutical compositions and compounds that possess inhibitory activity against β-adrenergic receptors and PDE.

  本发明提供了一种具有对β-肾上腺素能受体和磷酸二酯酶PDE，包括磷酸二酯酶3（PDE3）的抑制活性的化合物。本发明还提供了包含这些化合物的药物组合物；使用这些化合物治疗心血管疾病、中风、癫痫、眼科疾病或偏头痛的方法；以及制备具有对β-肾上腺素能受体和PDE抑制活性的药物组合物和化合物的方法。
• Substituierte (10H-Phenothiazin-10-yl)propyl-1-piperazin-Derivate, Verfahren zu deren Herstellung sowie Arzneimittel enthaltend diese Verbindungen
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0100033A1

  公开（公告）日：1984-02-08

  Die substituierten (10H-Phenothiazin-10-yl)propyl-1-piperazine der Formel worin R1 Wasserstoff, Halogen, Alkyl, Alkylthio, Alkoxy, Trihalomethyl oder die Gruppe -SO2NR2R3, X Sauerstoff oder Schwefel, m eine Zahl von 2-6, n und s unabhängig voneinander die Zahl 0 oder 1, A Alkylen und, falls X Sauerstoff bedeutet, auch 2-Hydroxytrimethylen und R2 und R3 unabhängig voneinander Wasserstoff oder Alkyl oder zusammen mit dem Stickstoffatom einen 5-, 6- oder 7gliedrigen unsubstituierten oder substituierten heterocyclischen Ring bedeuten, die Enantiomeren solcher Verbindungen, worin A 2-Hydroxytrimethylen bedeutet, und die pharmazeutisch verwendbaren Säureadditionssalze davon besitzen langanhaltende neuroleptische Wirkung und können demnach als langwirksame Antipsychotika, insbesondere in der Behandlung von Schizophrenie verwendet werden. Sie können durch Umsetzen eines 1-[3-(10H-Phenothiazin-10-yl)propyll-4-haloalkylpiperazins mit einem entsprechenden substituierten Phenol hergestellt werden.

  式中的取代(10H-吩噻嗪-10-基)丙基-1-哌嗪类 其中 R1为氢、卤素、烷基、烷硫基、烷氧基、三卤甲基或基团-SO2NR2R3，X为氧或硫，m为2-6的数字，n和s各自独立地为0或1，A为亚烷基，如果X为氧，则为2-羟基三亚甲基，R2和R3各自独立地为氢或烷基或与氮原子一起为5、6或7元未取代或取代的杂环、 这类化合物的对映体（其中 A 为 2-羟基三亚甲基）及其药学上可接受的酸加成盐具有长效神经抑制活性，因此可用作长效抗精神病药，尤其是用于治疗精神分裂症。它们可以通过 1-[3-(10H-吩噻嗪-10-基)丙基-4-卤代烷基哌嗪]与相应的取代苯酚反应制备。
• [EN] COMPOUNDS WITH MIXED PDE-INHIBITORY AND beta-ADRENERGIC ANTAGONIST OR PARTIAL AGONIST ACTIVITY FOR TREATMENT OF HEART FAILURE<br/>[FR] COMPOSES PRESENTANT UNE ACTIVITE MIXTE D'INHIBITION DE LA PDE ET D'ANTAGONISTE OU D'AGONISTE PARTIEL <supplemental>20041125</supplemental>EP0116948A2SYNTEX INC [US]198408291,27-29A1,25,37,40AEP0355583A2OTSUKA PHARMA CO LTD [JP]1990022872121X37XGB2190676ABRISTOL MYERS CO1987112510521165143X1,25,37XGB1465946ACIBA GEIGY AG19770302411311,23,12428mX1,25,37XEP0029992A1BOEHRINGER MANNHEIM GMBH [DE]198106101,92g,6hX1,25,37XDE2950479A1NATTERMANN A & CIE [DE]19810619811,32,3X1,25,37XUS5641783AKLEIN J PETER [US], et al19970624claims 1, 18 (column 97, line 5) and 21X1,25XGB1488330ASMITH KLINE FRENCH LAB19771012page 3, lines 32-37 and page 4, lines 1-16; claim 1X25,37XEP0138344A2SMITH KLINE FRENCH LAB [GB]19850424page 6, line 13- page 7, line 25X25,37XGB1567907ASMITH KLINE FRENCH LAB19800521page 5, lines 22-23; page 6, lines 51-52;X1XEGUCHI, YUKUO ET AL: "Studies on antiatherosclerotic agents. Synthesis of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone derivatives and related compounds", CHEMICAL & PHARMACEUTICAL BULLETIN , 39(3), 795-7 CODEN: CPBTAL; ISSN: 0009-2363, 1991, XP001194680EGUCHI, YUKUO ET ALStudies on antiatherosclerotic agents. Synthesis of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone derivatives and related compoundsCHEMICAL & PHARMACEUTICAL BULLETIN , 39(3), 795-7 CODEN: CPBTAL; ISSN: 0009-23631991compound 10 and table IX1,25,37XM.S. CHODNEKAR ET AL.: "Beta-Adrenergic blocking agents. 11. Heterocyclic analogs of pronethalol[2-isopropylamino-1-(2-naphthyl)ethanol]", JOURNAL OF MEDICINAL CHEMISTRY., vol. 15, no. 1, 1972, USAMERICAN CHEMICAL SOCIETY. WASHINGTON., pages 49 - 57, XP002292174M.S. CHODNEKAR ET AL.Beta-Adrenergic blocking agents. 11. Heterocyclic analogs of pronethalol[2-isopropylamino-1-(2-naphthyl)ethanol]JOURNAL OF MEDICINAL CHEMISTRY.USAMERICAN CHEMICAL SOCIETY. WASHINGTON.19721514957compound 30X37XGB1540628AOTSUKA PHARMA CO LTD197902141,83page 1, lines 6-24; examplesX1,25,37XCROWTHER A F ET AL: "BETA-ADRENERGIC BLOCKING AGENTS. 12. HETEROCYCLIC COMPOUNDS RELATEDTO PROPRANOLOL", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 15, no. 3, 1972, pages 260 - 266, XP000909966, ISSN: 0022-2623CROWTHER A F ET ALBETA-ADRENERGIC BLOCKING AGENTS. 12. HETEROCYCLIC COMPOUNDS RELATEDTO PROPRANOLOLJOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US19721530022-2623260266<table>VII</table>X37XDATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; NAKAGAWA, KAZUYUKI ET AL: "Carbostyril derivatives", XP002292176, retrieved from STN Database accession no. 1977:453098NAKAGAWA, KAZUYUKI ET ALCarbostyril derivativesCHEMABSCHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US1977:453098STNAabstract and compounds 61122-74-5, 61122-75-6, 63423-80-3, 63423-81-4X1,25,37XJPS51125291AOTSUKA PHARMA CO LTD19761101DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; NAKAGAWA, KAZUYUKI ET AL: "Carbostyril derivatives", XP002292177, retrieved from STN Database accession no. 1977:89632NAKAGAWA, KAZUYUKI ET ALCarbostyril derivativesCHEMABSCHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US1977:89632STNAabstract and compounds 61122-74-5 and 61122-75-6X1,25,37XJPS5168575AOTSUKA PHARMA CO LTD19760614DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; ISHIKAWA, HIROSHI ET AL: "Carbostyril derivatives", XP002292178, retrieved from STN Database accession no. 1978:509144ISHIKAWA, HIROSHI ET ALCarbostyril derivativesCHEMABSCHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US1978:509144STNAcompound 67358-84-3X1,25,37XJPS5350182AOTSUKA PHARMA CO LTD19780508DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SAKANO, KAZUHISA ET AL: "3,4-Dihydrocarbostyril derivatives", XP002292179, retrieved from STN Database accession no. 1979:405123SAKANO, KAZUHISA ET AL3,4-Dihydrocarbostyril derivativesCHEMABSCHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US1979:405123STNAcompounds 70386-53-7, 70386-41-3, 63423-80-3X1,25,37XJPS5416478AOTSUKA PHARMA CO LTD19790207DATABASE CHEMABS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; "Carbostyrils", XP002292180, retrieved from STN Database accession no. 1982:406175CarbostyrilsCHEMABSCHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US1982:406175STNAcompound 81994-29-8X1,25XJPS5742673AOTSUKA PHARMA CO LTD19820310WO8402908A1POS LAB [FR]1984080213191,4X1,25,37XKIKKAWA, HIDEO ET AL: "The role of the seventh transmembrane region in high affinity binding of a .beta.2-selective agonist TA-2005", MOLECULAR PHARMACOLOGY , 53(1), 128-134 CODEN: MOPMA3; ISSN: 0026-895X, 1998, XP001199449KIKKAWA, HIDEO ET ALThe role of the seventh transmembrane region in high affinity binding of a .beta.2-selective agonist TA-2005MOLECULAR PHARMACOLOGY , 53(1), 128-134 CODEN: MOPMA3; ISSN: 0026-895X1998compounds II and III; abstractX1,25,37XDEYRUP, M. D. ET AL: "Structure-affinity profile of 8-hydroxycarbostyril-based agonists that dissociate slowly from the .beta.2-adrenoceptor", NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY , 359(3), 168-177 CODEN: NSAPCC; ISSN: 0028-1298, 1999, XP001199515DEYRUP, M. D. ET ALStructure-affinity profile of 8-hydroxycarbostyril-based agonists that dissociate slowly from the .beta.2-adrenoceptorNAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY , 359(3), 168-177 CODEN: NSAPCC; ISSN: 0028-12981999compounds 10b, 10c, 10gX1,25,37XWO03015785A1ICOS CORP [US], et al20030227page 51, line 1, column 3PX1,25PXSIVAKUMAR, RAMAIYA ET AL: "Pharmacological evaluation of some new 1-substituted-4-hydroxy- phthalazines", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 37(10), 793-801 CODEN: EJMCA5; ISSN: 0223-5234, 2002, XP004393912SIVAKUMAR, RAMAIYA ET ALPharmacological evaluation of some new 1-substituted-4-hydroxy- phthalazinesEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY , 37(10), 793-801 CODEN: EJMCA5; ISSN: 0223-52342002compounds 5, 7 and 12 and table 1PX1,25PX
  申请人：ARTESIAN THERAPEUTICS INC

  公开号：WO2004050657A3

  公开（公告）日：2004-11-25