(3-Isocyanatopropoxy)benzene | 301530-53-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3-Isocyanatopropoxy)benzene
• 英文别名: 3-isocyanatopropoxybenzene
• CAS: 301530-53-0
• 化学式: C₁₀H₁₁NO₂
• mdl: MFCD18269725
• 分子量: 177.203
• InChiKey: BHNPMIFUYRTISC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-Isocyanatopropoxy)benzene 在 苯甲醚 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-[3,3-Diethyl-4-oxo-1-(3-phenoxy-propylcarbamoyl)-azetidin-2-yloxy]-benzoic acid
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003
• 作为产物：
  描述：

  sodium isocyanate 、 3-苯氧基溴丙烷 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (3-Isocyanatopropoxy)benzene
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003

文献信息

• [EN] 3-OXO-1, 3-DIHYDRO-INDAZOLE-2-CARBOXYLIC ACID AMIDE DERIVATIVES AS PHOSPHOLIPASE INHIBITORS<br/>[FR] UTILISATION DE DERIVES AMIDES D'ACIDE 3-OXO-1,3-DIHYDRO-INDAZOLE-2-CARBOXYLIQUE COMME INHIBITEURS DE LA PHOSPHOLIPASE
  申请人：LILLY CO ELI

  公开号：WO2004093872A1

  公开（公告）日：2004-11-04

  The present invention provides a compound of formula I (1) wherein; R, is selected from the group consisting of C5-C13alky1;:C,-C,2haloalkyl, C4­C,2alkenyl, C4-C12alkynyl, or C,- C5alkylcycloalkyl, C3-C8cycloalkyl, C,­ C5alkylheterocyclic, and aryl, wherein the, cycloalkyl, cycloalkenyl, heterocyclic and aryl substituents are optionally substituted with onf to three substituents independently selected from C,-C8a)kyl, C,-C8haloalkyl,`C2-CBalkenyl, C2-C8a)kynyl, phenyl, benzyl, hydroxy, C,-C5 alkoxy, (C}12)m000C,-Csalkyl, (CH2)mNRaRb, and C,­C4alkylcycloalkyl; wherein Wand Rb are independently selected from hydrogen, C,­CBalkyl, C2-CBalkenyl, C2-CBalkynyl, and C,- C5alkylcycloalkyl; R2 is hydrogen; R3, R4, R5, and R6, are independently selected from hydrogen, C,-C12alkyl, C2­C,2haloalkyl, C2-C,2 alkenyl, C2-C12alkynyl, C,-Ct2alkylaryl, C,-C12alkylcyclohexyl, C,­ C12alkylcyclopentyl, C,-C1zalkylheterocyclic, (CH2)m000H, (CH2)mC0(C,-C,o)alkyl, (CH2)m COO(C,-C,o)alkyl, (CH2)mCOO(C,-C,o)alkylaryl, C,-C,oalkylamino, halo, (CH2)mCONH2, (CH2)rCONRaRb, phenyl, or aryl wherein each of the phenyl or aryl groups is optionally substituted with one to three groups independently selected from CBalkyl, C,-CBhaloalkyl, C2-CBalkenyl, CZ CBalkynyl, phenyl, benzyl, hydroxy, C,-C5 alkoxy, (CH2)m000C,-Csalkyl, and C,-C4alkylcycloalkyl; and wherein m is 0, 1, 2, or 3; R7 is selected from the group consisting of hydrogen, C,-Cloalkyl, C,­C,ohaloalkyl, C2-C,oalkenyl, C2-C,oalkynyl, C,-C6alkylaryl, C,-C6alkylcyclohexyl, C - C6aikylcyclopentyl, C,-C6alkylheterocyclic, or aryl; or a pharmaceutically acceptable sal lvate thereofi together with the use of such compounds for inhibiting hepatic lipase and/or endothelial lipase activity for treatment, amelioration or prevention of hepatic lipase and/or endothelial lipase-mediated diseases.

  本发明提供了一种式子I（1）的化合物，其中R选自C5-C13烷基，C3-C12卤代烷基，C4-C12烯基，C4-C12炔基，或C1-C5烷基环烷基，C3-C8环烷基，C1-C5烷基杂环，和芳基，其中环烷基，环烯基，杂环和芳基取代基可选择地独立地被C1-C8烷基，C1-C8卤代烷基，C2-C8烯基，C2-C8炔基，苯基，苄基，羟基，C1-C5烷氧基，（C12）m000C1-C5烷基，（CH2）mNRaRb和C1-C4烷基环烷基取代，其中W和Rb独立地选择氢，C1-C6烷基，C2-C6烯基，C2-C6炔基和C1-C5烷基环烷基；R2为氢；R3、R4、R5和R6独立地选择氢，C1-C12烷基，C2-C12卤代烷基，C2-C12烯基，C2-C12炔基，C1-C12烷基芳基，C1-C12烷基环己基，C1-C12烷基环戊基，C1-C12烷基杂环，（ ）m000H，（ ）mCO（C1-C4）烷基，（ ）mCOO（C1-C4）烷基，（ ）mCOO（C1-C4）烷基芳基，C1-C4烷基氨基，卤素，（ ）mCONH2，（ ）rCONRaRb，苯基或芳基，其中苯基或芳基中的每个取代基可选择地独立地被C1-C8烷基，C1-C8卤代烷基，C2-C8烯基，C2-C8炔基，苯基，苄基，羟基，C1-C5烷氧基，（C12）m000C1-C5烷基和C1-C4烷基环烷基取代；其中m为0、1、2或3；R7选自氢，C1-C6烷基，C1-C6卤代烷基，C2-C6烯基，C2-C6炔基，C1-C6烷基芳基，C1-C6烷基环己基，C1-C6烷基环戊基，C1-C6烷基杂环或芳基；或其药学上可接受的盐；以及使用这样的化合物来抑制肝脏脂肪酶和/或内皮脂肪酶活性，用于治疗、缓解或预防肝脏脂肪酶和/或内皮脂肪酶介导的疾病。
• 3-oxo-1, 3-dihydro-indazole-2-carboxylic acid amide derivatives as phospholipase inhibitors
  申请人：Eacho Irving Patrick

  公开号：US20060211755A1

  公开（公告）日：2006-09-21

  The present invention provides a compound of formula I (1) wherein; R, is selected from the group consisting of C 5 -C 13 alkyl; C,—C, 2 haloalkyl, C 4 C,2alkenyl, C 4 -C 12 alkynyl, or C,—C5alkylcycloalkyl, C3-C8cycloalkyl, C, C 5 alkylheterocyclic, and aryl, wherein the, cycloalkyl, cycloalkenyl, heterocyclic and aryl substituents are optionally substituted with one to three substituents independently selected from C,—C 8 a)kyl, C,—C 8 haloalkyl, ′C 2 -C B alkenyl, C2-C 8 a)kynyl, phenyl, benzyl, hydroxy, C,—C5 alkoxy, (C}12) m 000C,—Csalkyl, (CH2) m NR a R b , and C,C 4 alkylcycloalkyl; wherein W and R b are independently selected from hydrogen, C,C B alkyl, C 2 -C B alkenyl, C 2 -C B alkynyl, and C,—C5alkylcycloalkyl; R 2 is hydrogen; R3, R4, R5, and R6, are independently selected from hydrogen, C,—C 12 alkyl, C 2 C,2haloalkyl, C2-C,2 alkenyl, C 2 -C 12 alkynyl, C,—C 12 alkylaryl, C,—C 12 alkylcyclohexyl, C, C 12 alkylcyclopentyl, C,—C 12 alkylheterocyclic, (CH2) m 000H, (CH2) m C0(C,—C,o)alkyl, (CH 2 ) m COO(C,—C ,o )alkyl, (CH2) m COO(C 1 -C ,o )alkylaryl, C,—C ,o alkylamino, halo, (CH 2 ) m CONH 2 , (CH 2 ) r CONRaR b , phenyl, or aryl wherein each of the phenyl or aryl groups is optionally substituted with one to three groups independently selected from C B alkyl, C,—C B haloalkyl, C 2 -C B alkenyl, C Z C B alkynyl, phenyl, benzyl, hydroxy, C,—C5 alkoxy, (CH2) m 000C,—Csalkyl, and C,—C4alkylcycloalkyl; and wherein m is 0, 1, 2, or 3; R7 is selected from the group consisting of hydrogen, C,—C lo alkyl, C,C ,o haloalkyl, C 2 -C ,o alkenyl, C 2 -C ,o alkynyl, C,—C 6 alkylaryl, C,—C 6 alkylcyclohexyl, C—C 6 aikylcyclopentyl, C,—C 6 alkylheterocyclic, or aryl; or a pharmaceutically acceptable sallvate thereofi together with the use of such compounds for inhibiting hepatic lipase and/or endothelial lipase activity for treatment, amelioration or prevention of hepatic lipase and/or endothelial lipase-mediated diseases.

  本发明提供一种公式I（1）的化合物，其中：R选自C5-C13烷基；C，C2卤代烷基，C4-C2烯基，C4-C12炔基，或C，C5烷基环烷基，C3-C8环烷基，C，C5烷基杂环基和芳基，其中环烷基，环烯基，杂环和芳基取代基可选地独立地被选自C，C8烷基，C，C8卤代烷基，C2-CB烯基，C2-C8炔基，苯基，苄基，羟基，C，C5烷氧基，（C}12）m000C，C5烷基，（CH2）mNRaRb和C，C4烷基环烷基的一个到三个取代基所取代；其中W和Rb独立地选自氢，C，C8烷基，C2-CB烯基，C2-CB炔基和C，C5烷基环烷基；R2为氢；R3，R4，R5和R6独立地选自氢，C，C12烷基，C2-C，2卤代烷基，C2-C，2烯基，C2-C12炔基，C，C12烷基芳基，C，C12烷基环己基，C，C12烷基环戊基，C，C12烷基杂环基，（ ）m000H，（ ）mC0（C，C，o）烷基，（ ）mCOO（C，C，o）烷基，（ ）mCOO（C1-C，o）烷基芳基，C，C，o烷基氨基，卤素，（ ）mCONH2，（ ）rCONRaRb，苯基或芳基，其中苯基或芳基中的每个苯基或芳基可选地独立地被选自C烷基，C，C卤代烷基，C2-CB烯基，CZCB炔基，苯基，苄基，羟基，C，C5烷氧基，（ ）m000C，C5烷基和C，C4烷基环烷基的一个到三个基团所取代；其中m为0、1、2或3；R7选自氢，C，C6烷基，C，C6卤代烷基，C2-C，o烯基，C2-C，o炔基，C，C6烷基芳基，C，C6烷基环己基，C-C6烷基环戊基，C，C6烷基杂环基或芳基；或其药学上可接受的盐；以及使用这种化合物来抑制肝脏脂酶和/或内皮脂酶活性，用于治疗、改善或预防肝脏脂酶和/或内皮脂酶介导的疾病。
• Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol
  作者：Bassem Sadek、Safa Shehab、Małgorzata Więcek、Dhanasekaran Subramanian、Mohamed Shafiullah、Katarzyna Kieć-Kononowicz、Abdu Adem

  DOI：10.1016/j.bmcl.2013.06.075

  日期：2013.9

  Ligands targeting central histamine H-3 receptors (H(3)Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs. Following administration of the H3R ligands 1-13 (5, 10 and 15 mg/kg, ip) there was a significant dose dependent reduction in MES-induced seizure duration. The protective action observed for the pentenyl carbamate derivative 4, the most protective H3R ligand among 1-13, was significantly higher (P<0.05) than that of standard H3R antagonist THP, and was reversed when rats were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist Pyrilamine (PYR) (10 mg/kg). In addition, subeffective dose of H3R ligand 4 (5 mg/kg, ip) significantly potentiated the protective action in rats pretreated with PHT (5 mg/kg, ip), a dose without appreciable protective effect when given alone. In contrast, pretreatment with H3R ligand 4 (10 mg/kg ip) failed to modify PTZ-kindled convulsion, whereas the reference drug PHT was found to fully protect PTZ-induced seizure. These results indicate that some of the investigated imidazole-based H3R ligands 1-13 may be of future therapeutic value in epilepsy. (C) 2013 Elsevier Ltd. All rights reserved.
• EP1610779A1
  申请人：——

  公开号：EP1610779A1

  公开（公告）日：2006-01-04
• 3-OXO-1,3-DIHYDRO-INDAZOLE-2-CARBOXYLIC ACID AMIDE DERIVATIVES AS PHOSPHOLIPASE INHIBITORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1610779B1

  公开（公告）日：2009-09-09