7-(3-chloropropoxy)chromen-4-one | 105277-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 7-(3-chloropropoxy)chromen-4-one
• 英文别名: 7-(3-chloropropoxy)-4H-1-benzopyran-4-one；4H-1-Benzopyran-4-one, 7-(3-chloropropoxy)-
• CAS: 105277-69-8
• 化学式: C₁₂H₁₁ClO₃
• 分子量: 238.671
• InChiKey: TXKUJOMDRORGNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-(3-chloropropoxy)chromen-4-one 在 sodium iodide 作用下， 以 甲苯 、 丁酮 为溶剂， 反应 19.0h， 生成 7-{3-[(3-Hydroxy-benzyl)-methyl-amino]-propoxy}-chromen-4-one
  参考文献：
  名称：

  Acetylcholinesterase Inhibitors:  Synthesis and Structure−Activity Relationships of ω-[N-Methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl Derivatives

  摘要：

  Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.

  DOI：

  10.1021/jm9810046
• 作为产物：
  描述：

  1-[4-(3-氯丙氧基)-2-羟基苯基]乙酮 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 3.75h， 生成 7-(3-chloropropoxy)chromen-4-one
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics

  摘要：

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

  DOI：

  10.1021/jm950894b

文献信息

• 4-p-fluorobenzoyl-1-piperidinyl-propoxy-chromen-4-one derivatives, their
  申请人：Ferrer Internacional, S.A.

  公开号：US05643927A1

  公开（公告）日：1997-07-01

  The present invention relates to new chromene compounds of the general formula (I): ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen, alkyl having from 1 to 4 carbon atoms, halogen, trifluoromethyl, optionally substituted phenyl, or hydroxymethyl, as well as their pharmaceutically acceptable addition salts. These compounds are useful in the treatment of psychosis and schizophrenia.

  本发明涉及一般式（I）的新的咔咯酮化合物：其中R₁和R₂为氢、具有1至4个碳原子的烷基、卤素、三氟甲基、可选取代的苯基或羟甲基，以及它们的药用可接受的加合物盐。这些化合物在治疗精神病和精神分裂症中有用。
• A new efficient synthesis of 3-(hydroxymethyl)-4<i>H</i>-chromen-4-ones
  作者：Jordi Bolós、Teresa Loscertales、Joan Nieto、Aurelio Sacristán、José A. Ortiz

  DOI：10.1002/jhet.5570370529

  日期：2000.9

  An efficient and versatile synthesis of variously substituted 3-(hydroxymethyl)-4H-chromen-4-ones is reported. The compounds are prepared by hydroxymethylation of the precursor 2-hydroxy-4-chromanones followed by acid dehydration.

  报道了各种取代的3-（羟甲基）-4 H-铬烯-4-酮的有效和通用的合成。通过将前体2-羟基-4-二氢呋喃酮进行羟甲基化，然后进行酸脱水来制备化合物。
• 4H-1-benzopyran-4-ones and their sulfur containing analogs
  申请人：Warner-Lambert Company

  公开号：US04678787A1

  公开（公告）日：1987-07-07

  Novel 4H-1-benzopyran-4-ones and their sulfur containing analogs are disclosed which are efficacious for the treatment of psychosis including schizophrenia.

  揭示了一种有效治疗精神病，包括精神分裂症的Novel 4H-1-苯并吡喃-4-酮及其含硫类似物。
• [EN] 4-(6-FLUORO-1,2-BENZISOXAZOLYL)-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF PSYCHOSIS, SCHIZOPHRENIA AND ANXIETY<br/>[FR] DERIVES DE 4-(6-FLUORO-1,2-BENZISOXAZOLYL)-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE, LEUR PREPARATION ET LEUR UTILISATION DANS LE TRAITEMENT DES PSYCHOSES, DE LA SCHIZOPHRENIE ET DE L'ANXIETE
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：WO1996032389A1

  公开（公告）日：1996-10-17

  (EN) The present invention relates to 4-(6-fluoro-1,2-benzisoxazolyl)-1-piperidinyl-propoxy-chromen-4-one derivatives having formula (I), wherein R is hydrogen or alkyl having 1 to 4 carbon atoms optionally substituted by hydroxyl, as well as their pharmaceutically acceptable addition salts, which are useful in the treatment of psychosis, schizophrenia and anxiety.(FR) La présente invention décrit des dérivés de 4-(6-fluoro-1,2-benzisoxazolyl)-1-pipéridinyl-propoxy-chromen-4-one de formule (I), dans laquelle R représente hydrogène ou alkyle ayant de 1 à 4 atomes de carbone facultativement substitués par hydroxyle, ainsi que leurs sels d'addition pharmaceutiquement acceptables, utilisés dans le traitement des psychoses, de la schizophrénie et de l'anxiété.

  本发明涉及具有式(I)的4-(6-氟-1,2-苯并异噁唑基)-1-哌啶基-丙氧基-香豆素衍生物，其中R为氢或烷基，烷基含有1至4个碳原子，可选择地被羟基取代，以及它们的药学上可接受的加合物盐，用于治疗精神病、精神分裂症和焦虑症。
• Novel 4H-1-benzopyran-4-ones and their sulphur containing analogs
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0190015A1

  公开（公告）日：1986-08-06

  There are disclosed novel 4H -1-benzopyran-4-ones and their sulphur containing analogs which are effecacious for the treatment of psychosis including schizophrenia The compounds have the formula (I) wherein X is oxygen or sulfur, n is 2, 3, 4 or 5 and R is or in which Ar is an aryl.

  已公开的新型 4H -1- 苯并吡喃-4-酮及其含硫类似物可有效治疗包括精神分裂症在内的精神错乱。