4-(3-chloro-4-ethoxycarbonylmethoxy-phenyl)-4-oxo-butyric acid | 103415-67-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-chloro-4-ethoxycarbonylmethoxy-phenyl)-4-oxo-butyric acid
• 英文别名: 4-[3-chloro-4-(ethoxycarbonylmethoxy)phenyl]-4-oxobutyric acid；4-[3-chloro-4-(2-ethoxy-2-oxoethoxy)phenyl]-4-oxobutanoic acid
• CAS: 103415-67-4
• 化学式: C₁₄H₁₅ClO₆
• 分子量: 314.722
• InChiKey: JHSJDSOOCASHRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-ethoxycarbonylmethoxy-phenyl)-4-oxo-butyric acid 在 肼 作用下， 以 乙醇 为溶剂， 反应 3.25h， 以82%的产率得到6-[3-chloro-4-(ethoxycarbonylmethoxy)phenyl]-4,5-dihydro-3(2H)-pyridazinone
  参考文献：
  名称：

  [EN] DIHYDROPYRIDINE COMPOUNDS HAVING SIMULTANEOUS ABILITY TO BLOCK L-TYPE CALCIUM CHANNELS AND TO INHIBIT PHOSPHODIESTERASE TYPE 3 ACTIVITY
  [FR] COMPOSES DE DIHYDROPYRIDINE PRESENTANT A LA FOIS LA CAPACITE DE BLOQUER DES CANAUX CALCIQUES DE TYPE L ET LA CAPACITE D'INHIBER L'ACTIVITE DE TYPE 3 DE LA PHOSPHODIESTERASE

  摘要：

  本发明提供了具有对PDE-3和L型钙通道具有抑制活性的化合物。本发明还提供了包含这些化合物的药物组合物以及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。

  公开号：

  WO2004033444A1
• 作为产物：
  描述：

  丁二酸酐 、 2-(2-氯苯氧基)乙酸乙酯 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 生成 4-(3-chloro-4-ethoxycarbonylmethoxy-phenyl)-4-oxo-butyric acid
  参考文献：
  名称：

  Pyridazinone derivatives, their preparation and use

  摘要：

  式(I)的化合物：##STR1##（其中Q是氧或硫，虚线是单键或双键，A是烷基，R.sup.1-R.sup.5是各种原子或有机基团）具有优异的增强心肌收缩能力和多种其他性质，可用于治疗心脏疾病。

  公开号：

  US04914093A1

文献信息

• Compounds having simultaneous ability to block L-type calcium channels and to inhibit phosphodiesterase type 3 activity
  申请人：ARTESIAN THERAPEUTICS, INC.

  公开号：US20040242648A1

  公开（公告）日：2004-12-02

  The present invention provides compounds that possess inhibitory activity against PDE-3 and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating cardiovascular disease, stroke, epilepsy, ophthalmic disorder or migraine.

  本发明提供了具有对PDE-3和L型钙通道的抑制活性的化合物。本发明还提供了包含这种化合物的药物组合物和使用这种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。
• METHODS OF MAKING COMPOUNDS HAVING A BETA-ADRENERGIC INHIBITOR AND A LINKER AND METHODS OF MAKING COMPOUNDS HAVING A BETA-ADRENERGIC INHIBITOR, A LINKER AND A PHOSPHODIESTERASE INHIBITOR
  申请人：Chen Gang

  公开号：US20080262226A1

  公开（公告）日：2008-10-23

  A method is provided for making compounds comprising a beta-adrenergic inhibiting moiety and a linking moiety, the method comprising: a) reacting a compound of formula (A): (R 1 —(CH—O—CH 2 )) with at least one of NH 3 , NH 4 , NH 4 ClNH 3 and R 12′ NH 2 thereby forming a compound of formula (B): (R 1 —CH(OH)—CH 2 —NHR 12′ ); and b) reacting a compound of formula (B) with a compound of formula (C): (R 3 ═O), thereby forming a compound of formula (D): (R 1 —COH—CH 2 —N(R 3 )(R 12′ )), wherein R 1 comprises the beta-adrenergic inhibiting moiety or comprises the beta-adrenergic inhibiting moiety when bonded to —COH—CH 2 —N(R 12′ )— of formula (D); R 3 comprises the linking moiety and is bonded to the =0 of formula (C) via a carbon atom; and R 12′ is selected from hydrogen and a protecting group.

  提供了一种制备含有β-肾上腺素受体抑制基团和连接基团的化合物的方法，该方法包括：a)将式（A）的化合物：（R1-（CH-O-CH2））与NH3、NH4、NH4ClNH3和R12'NH2中的至少一种反应，从而形成式（B）的化合物：（R1-CH（OH）-CH2-NHR12'）；b)将式（B）的化合物与式（C）的化合物反应：（R3═O），从而形成式（D）的化合物：（R1-COH-CH2-N（R3）（R12'）），其中R1包括β-肾上腺素受体抑制基团，或者在与式（D）的—COH-CH2-N（R12'）—结合时包括β-肾上腺素受体抑制基团；R3包括连接基团，并通过碳原子与式（C）的=0结合；R12'选择自氢和保护基团。
• 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。
• WO2008/58198
  申请人：——

  公开号：——

  公开（公告）日：——
• [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