| 1257245-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1257245-99-0
• 化学式: C₁₀H₁₀O
• 分子量: 146.189
• InChiKey: JKBHNBLPNXPHAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,4-二甲基吡咯 、 在 C₄₅H₃₁O₄P 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 30.0h， 以64%的产率得到
  参考文献：
  名称：

  手性螺磷酸催化乙烯酮与 N-H 吡咯的对映选择性反应

  摘要：

  在手性螺磷酸催化剂存在下，双取代乙烯酮与 N-H 吡咯发生不对称反应，得到对映体富集的C-酰化吡咯，其带有 α-立体碳中心。所描述的反应构成了烯酮与碳基亲核试剂的催化不对称反应的罕见例子。

  DOI：

  10.1039/d1cc05307h
• 作为产物：
  描述：

  2-间甲苯基丙酸 在 氯化亚砜 、 二甲基十二/十四烷基叔胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 31.17h， 生成
  参考文献：
  名称：

  Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition

  摘要：

  Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-beta-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme alpha,beta-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC50 approximate to 30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.

  DOI：

  10.1021/ja300799t

文献信息

• Enantioselective formal [2+2] cycloaddition of ketenes with nitroso compounds catalyzed by N-heterocyclic carbenes
  作者：Tong Wang、Xue-Liang Huang、Song Ye

  DOI：10.1039/c0ob00249f

  日期：——

  Chiral N-heterocyclic carbenes were found to be efficient catalysts for the formal [2+2] cycloaddition reaction of alkyl(aryl)ketenes and nitroso compounds to give the corresponding 1,2-oxazetidin-3-ones in moderate to good yields with high enantioselectivities. Reductive ring-opening of the oxazetidinones give the corresponding α-hydroxy acid derivatives in good yields.

  发现手性N-杂环卡宾是有效的催化剂，用于烷基（芳基）乙烯酮和亚硝基化合物的正式[2 + 2]环加成反应，以中等至良好的收率，高收率得到相应的1,2-氧杂az啶-3-酮对映选择性。恶唑烷二酮的还原性开环给出相应的α-羟酸 衍生品收益率高。
• 2-(PHENYL OR HETEROCYCLIC)-1H-PHENANTRHO[9,10-D]IMIDAZOLES AS MPGES-1 INHIBITORS
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1828143B1

  公开（公告）日：2013-03-20
• [EN] 2-(PHENYL OR HETEROCYCLIC)-1H-PHENANTRHO[9,10-D]IMIDAZOLES AS MPGES-1 INHIBITORS<br/>[FR] 2-(PHENYL OU HETEROCYCLIQUE)-1H-PHENANTRHO[9,10-D]IMIDAZOLES UTILISEES COMME INHIBITEURS DE LA MPGES-1
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2007059610A1

  公开（公告）日：2007-05-31

  [EN] The invention encompasses novel compounds of Formula (I) or pharmaceutically acceptable salts thereof. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful to treat pain and/or inflammation from a variety of diseases or conditions, such as osteoarthritis, rheumatoid arthritis and acute or chronic pain. Methods of treating diseases or conditions mediated by the mPGES-1 enzyme and pharmaceutical compositions are also encompassed.
  [FR] L'invention porte sur de nouveaux composés de la formule (I) ou sur des sels pharmaceutiquement acceptables de ces derniers. Les composés de l'invention sont des inhibiteurs de l'enzyme prostaglandine E synthase-1 microsomale (mPGES-1) et sont par conséquent utilisés pour traiter la douleur et/ou l'inflammation provoquées par une variété d'états et de pathologies, tels que l'ostéoarthrite, l'arthrite rhumatoïde et la douleur aiguë ou chronique. L'invention se rapporte également à des procédés permettant de traiter des états ou pathologies médiés par l'enzyme mPGES-1 et à des compositions pharmaceutiques.
• [EN] METHODS FOR TREATING OR PREVENTING NEOPLASIAS<br/>[FR] PROCÉDÉS PERMETTANT DE TRAITER OU DE PRÉVENIR DES NÉOPLASIES
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2007124589A1

  公开（公告）日：2007-11-08

  [EN] The present invention is directed to a method for treating or preventing a neoplasia in a human patient in need of such treatment comprising administering to the patient a compound that inhibits microsomal prostaglandin E synthase-1 in an amount that is effective for treating or preventing the neoplasia.
  [FR] La présente invention concerne un procédé permettant de traiter ou de prévenir une néoplasie chez un patient humain nécessitant un tel traitement; elle comprenant l'administration au patient d'un composé inhibant la prostaglandine E synthase-1 microsomale en quantité efficace pour le traitement ou la prévention de la néoplasie.
• [EN] AlphaZetaAlpha-beta-LACTAM COMPOUNDS AND METHODS OF USING<br/>[FR] COMPOSÉS AZA-Beta-LACTAMES ET PROCÉDÉS D'UTILISATION
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2013152272A1

  公开（公告）日：2013-10-10

  The invention is directed to methods of modulation of serine hydrolase ABHD10, which can be selective with respect to other serine hydrolases such as PME-1. The compounds of the invention, or compounds useful in practice of a method of the invention, are aza-β-lactams, of which the (R)-enantiomer is preferred, for modulation of ABHD10. Methods of preparation are provided comprising the cycloaddition of dialkylazodicarboxylates with ketenes using the catalyst PPY*. The invention provides methods of treatment of conditions in patients for which modulation of ABHD10 is indicated, including pain, inflammation, metabolic disorders, solid tumors, or obesity.