phenyl benzo[d][1,3]dioxol-5-ylcarbamate | 176906-00-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: phenyl benzo[d][1,3]dioxol-5-ylcarbamate
• 英文别名: LASSBio-1213；phenyl 1,3-benzodioxol-5-ylcarbamate；phenyl N-(1,3-benzodioxol-5-yl)carbamate
• CAS: 176906-00-6
• 化学式: C₁₄H₁₁NO₄
• 分子量: 257.246
• InChiKey: CRPWYDODWVNEQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  368.7±42.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  phenyl benzo[d][1,3]dioxol-5-ylcarbamate 在 盐酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 (E)-N-(benzo[d][1,3]dioxol-5-yl)-2-(4-isopropylbenzylidene)hydrazinecarboxamide
  参考文献：
  名称：

  Design, synthesis and in vitro trypanocidal and leishmanicidal activities of novel semicarbazone derivatives

  摘要：

  Trypanosomatids are protozoan parasites that cause various diseases in human, such as leishmaniasis, Chagas disease and sleeping sickness. The highly syntenic genomes of the trypanosomatid species lead the assumption that they can encode similar proteins, indicating the possibility to design new antitrypanosomatid drugs with dual trypanosomicidal and leishmanicidal activities. In this work a series of compounds (6a-h and 7a-h), containing a semicarbazone scaffold as a peptide mimetic framework, was designed and synthesized. From this series compound 7g (LASSBio-1483) highlighted, showing dual in vitro trypanosomicidal and leishmanicidal activities, with potency similar to the standard drugs nifurtimox and pentamidine. This data, taken together with its good in silico druglikeness profile and its great chemical and plasma stability, make LASSBio-1483 (7g) a new antitrypanosomatid lead-candidate. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.05.046
• 作为产物：
  描述：

  3,4-亚甲二氧基苯胺 、 氯甲酸苯酯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到phenyl benzo[d][1,3]dioxol-5-ylcarbamate
  参考文献：
  名称：

  氨基甲酸酯衍生物作为脂肪酸酰胺水解酶和单酰基甘油脂肪酶抑制剂的合成与评价

  摘要：

  脂肪酸酰胺水解酶 (FAAH) 和单酰基甘油脂肪酶 (MAGL) 是内源性大麻素、anandamide (AEA) 和 2-花生四烯酸甘油的主要分解代谢酶。大量研究表明，FAAH 和 MAGL 在调节各种中枢神经系统活动方面发挥着重要作用；因此，小分子 FAAH/MAGL 抑制剂的开发是一个活跃的研究领域。几种具有氨基甲酸酯支架的小分子被记录为潜在的 FAAH/MAGL 抑制剂。在这里，我们设计并合成了一系列开链和环状氨基甲酸酯，并评估了它们的双重 FAAH-MAGL 抑制特性。苯基 [4-(哌啶-1-基甲基)苯基]氨基甲酸酯 ( 2e ) 成为最有效的 MAGL 抑制剂 (IC 50  = 19 nM)，苄基 (1 H-苯并[d ]imidazol-2-yl)carbamate ( 3h ) 是最有效的 FAAH 抑制剂 (IC 50  = 55 nM)，苯基 (6-fluorobenzo[

  DOI：

  10.1002/ardp.202200081

文献信息

• [EN] ISOINDOLINONE COMPOUNDS<br/>[FR] COMPOSÉS D'ISO-INDOLINONE
  申请人：MONTE ROSA THERAPEUTICS

  公开号：WO2021069705A1

  公开（公告）日：2021-04-15

  Disclosed herein is a compound or pharmaceutically acceptable salts or stereoisomers thereof of of formula I wherein X1 is linear or branched C1-6 alkyl, C3-6 cycloalkyl, -C1-6 alkyl C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl C6-10 aryl, C1-6 alkyl 5-10 membered heteroaryl, wherein X1 is unsubstituted or substituted with one or more of halogen, linear or branched C1-6 alkyl, linear or branched C1-6 heteroalkyl, CF3, CHF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6 alkylamino, -CN, -N(H)C(O)-C1- 6alkyl, -OC(O)-C1-6alkyl, -OC(O)-C1-4alkylamino, -C(O)O-C1-6alkyl, -COOH, - CHO, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-6 alkoxy or C1-6 alkylhydroxy; X2 is hydrogen, C6-10 aryl, 5-10 membered heteroaryl, -O-(5-10 membered heteroaryl), 4-8 membered heterocycloalkyl, C1-4 alkyl 4-8 membered heterocycloalkyl, -O-(4-8 membered heterocycloalkyl), -O-C1-4 alkyl-(4-8 membered heterocycloalkyl), -OC(O)-C1-4alkyl-4-8 membered heterocycloalkyl or C6 aryloxy, wherein X2 is unsubstituted or substituted with one or more of linear or branched C1-6 alkyl, NH2, NMe2 or 5-6 membered heterocycloalkyl; n is 0, 1 or 2.

  本公开涉及一种化合物或药用可接受盐或其立体异构体，其化学式为I，其中X1为直链或支链的C1-6烷基，C3-6环烷基，-C1-6烷基C3-6环烷基，C6-10芳基，5-10成员杂芳基，C1-6烷基C6-10芳基，C1-6烷基5-10成员杂芳基，其中X1未取代或取代为一个或多个卤素，直链或支链的C1-6烷基，直链或支链的C1-6杂烷基，CF3，CHF2，-O-CHF2，-O-(CH2)2-OMe，OCF3，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-OC(O)-C1-4烷基氨基，-C(O)O-C1-6烷基，-COOH，-CHO，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-6烷氧基或C1-6烷基羟基；X2为氢，C6-10芳基，5-10成员杂芳基，-O-(5-10成员杂芳基)，4-8成员杂环烷基，C1-4烷基4-8成员杂环烷基，-O-(4-8成员杂环烷基)，-O-C1-4烷基-(4-8成员杂环烷基)，-OC(O)-C1-4烷基-4-8成员杂环烷基或C6芳氧基，其中X2未取代或取代为一个或多个直链或支链的C1-6烷基，NH2，NMe2或5-6成员杂环烷基；n为0、1或2。
• [EN] TETRAHYDRO-NAPHTHALENE AND UREA DERIVATIVES<br/>[FR] DERIVES DE TETRAHYDRO-NAPHTHALENE ET D'UREE
  申请人：BAYER HEALTHCARE AG

  公开号：WO2005040100A1

  公开（公告）日：2005-05-06

  This invention relates to tetrahydro-naphthalene and urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene and urea derivatives of the present invention have vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD). BHC 03 2 001-Foreign-Countries - 66 - BHC 03 2 001-Foreign-Countries - 65 -

  这项发明涉及四氢萘和脲衍生物及其盐，这些物质可作为药物制剂的活性成分。本发明的四氢萘和脲衍生物具有辣椒素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗与VR1活性相关的泌尿系统疾病或紊乱，如膀胱过度活动（过度活跃膀胱）、尿失禁、神经源性膀胱过度活动（膀胱过度反射）、特发性膀胱过度活动（膀胱不稳定）、良性前列腺增生、下尿路症状；慢性疼痛、神经病性疼痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风，以及哮喘和慢性阻塞性肺病（COPD）等炎症性疾病。BHC 03 2 001-外国国家 - 66 - BHC 03 2 001-外国国家 - 65 -
• Palladium-Catalyzed Cross-Coupling of Aryl Chlorides and Triflates with Sodium Cyanate: A Practical Synthesis of Unsymmetrical Ureas
  作者：Ekaterina V. Vinogradova、Brett P. Fors、Stephen L. Buchwald

  DOI：10.1021/ja305212v

  日期：2012.7.11

  chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction, including the first demonstration

  报道了一种钯催化芳基氯和三氟甲磺酸酯与氰酸钠交叉偶联的有效方法。该协议允许在一锅中合成不对称的 N,N'-di-和 N,N,N'-三取代脲，并且可以容忍多种功能组。通过对反应的金属转移和还原消除步骤的研究，包括从芳基钯异氰酸酯络合物中还原消除生成异氰酸芳基酯的首次演示，深入了解了芳基异氰酸酯的形成机制。
• Tetradydro-Naphthalene And Urea Derivatives
  申请人：Bouchon Axel

  公开号：US20080045546A1

  公开（公告）日：2008-02-21

  This invention relates to tetrahydro-naphthalene and urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene and urea derivatives of the present invention have vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor overactivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

  本发明涉及四氢萘和脲衍生物及其盐，其作为制药制剂的活性成分具有vanilloid受体（VR1）拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗泌尿系统疾病或障碍，如膀胱过度活动（过度活动膀胱），尿失禁，神经源性膀胱过度活动（膀胱过度反射），特发性膀胱过度活动（膀胱不稳定），良性前列腺增生和下尿路症状；慢性疼痛，神经病性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，疼痛，神经损伤，缺血，神经退行性疾病，中风以及哮喘和慢性阻塞性肺（或气道）疾病（COPD）等炎症性疾病。
• [EN] PHARMACEUTICAL COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF A DISEASE OR DISORDER CAUSED BY OR ASSOCIATED WITH ONE OR MORE PREMATURE TERMINATION CODONS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DESTINÉES À ÊTRE UTILISÉES POUR PRÉVENIR OU TRAITER UNE MALADIE OU UN TROUBLE PROVOQUÉ PAR OU ASSOCIÉ À UN OU PLUSIEURS CODONS DE TERMINAISON PRÉMATURÉS
  申请人：MONTE ROSA THERAPEUTICS AG

  公开号：WO2022200857A1

  公开（公告）日：2022-09-29

  The present disclosure relates to a. compound of formula I or a. pharmaceutically acceptable salt thereof Formula I wherein A is Formula II X1is linear or branched C1-6alkyl, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X1is unsubstituted or substituted with one or more of halogen, linear or branched C1-6alkyl, linear or branched C1-6heteroalkyl, CF3, CHF2, CMeF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6alkylamino, -CN, -N(H)C(O)-C1-6alkyl, - OC(O)-C1-6alkyl, -OC(O)-C1-4alkylamino, -C(O)O-C1-6alkyl, -COOH, -CHO, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-6alkoxy or Cue alkylhydroxy; or X1together with X4forms a 4-8 membered heterocycloalkyl, which is unsubstituted or substituted with one or more of halogen, linear or branched -C1-6alkyl, CF3, CHF2, CMeF2, -O-(CH2)2-OMe, OCF3, OCHF2, C1-6alkylamino, -CN, -N(H)C(O)-C1-6alkyl, -OC(O)-C1-6alkyl, -C(O)O-C1-6alkyl, -COOH, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-4alkylhydroxy, or C1-4alkoxy; X2is hydrogen, C3-6cycloalkyl, C6-10aryl, 5-10 membered heteroaryl, 4-8 membered heterocycloalkyl, wherein X2is unsubstituted or substituted with one or more of linear or branched Cue alkyl, -C1-4alkoxy, NH2, NMe2, halogen, CF3, CHF2, CMeF2, -O-(CH2)2-OMe, OCF3, OCHF2, CM alkylhydroxy, X3is -NH-, -O-; X4is -NH-, - CH2-; L1is a covalent bond, C1-6alkyl, which is unsubstituted or substituted with one or more of C1-4alkyl, halogen; L2is a covalent bond, Cue alkyl, which is unsubstituted or substituted with one or more of CM alkyl, halogen; L3is a covalent bond, -O-, - C1-4alkoxy or C1-6alkyl, which is unsubstituted or substituted with one or more of C1-4alkyd, halogen, for use in the prevention and treatment of a disease or disorder caused by or associated with one or more premature termination codons in a monotherapy or in a combined therapy with an aminoglycoside or a. pharmaceutically acceptable salt thereof.

  本公开涉及式I的化合物或其药学上可接受的盐，其中A为式II，X1为线性或支链C1-6烷基，C3-6环烷基，C6-10芳基，5-10成员杂芳基，4-8成员杂环烷基，其中X1未取代或取代有卤素，线性或支链C1-6烷基，线性或支链C1-6杂烷基，CF3，CHF2，CMeF2，-O-CHF2，-O-(CH2)2-OMe，OCF3，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-OC(O)-C1-4烷基氨基，-C(O)O-C1-6烷基，-COOH，-CHO，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-6烷氧基或Cue烷基羟基；或X1与X4共同形成未取代或取代有卤素，线性或支链C1-6烷基，CF3，CHF2，CMeF2，-O-(CH2)2-OMe，OCF3，OCHF2，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-C(O)O-C1-6烷基，-COOH，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-4烷基羟基或C1-4烷氧基的4-8成员杂环烷基；X2为氢，C3-6环烷基，C6-10芳基，5-10成员杂芳基，4-8成员杂环烷基，其中X2未取代或取代有线性或支链Cue烷基，-C1-4烷氧基，NH2，NMe2，卤素，CF3，CHF2，CMeF2，-O-(CH2)2-OMe，OCF3，OCHF2，CM烷基羟基，X3为-NH-，-O-；X4为-NH-，-CH2-；L1为共价键，C1-6烷基，未取代或取代有C1-4烷基，卤素；L2为共价键，Cue烷基，未取代或取代有CM烷基，卤素；L3为共价键，-O-，-C1-4烷氧基或C1-6烷基，未取代或取代有C1-4烷基，卤素，用于单一疗法或与氨基糖苷类药物或其药学上可接受的盐联合疗法预防和治疗由一个或多个过早终止密码子引起或相关的疾病或障碍。