噁唑并[5,4-c]吡啶-2(1h)-酮 | 68523-29-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶唑并吡啶类
• 中文名称: 噁唑并[5,4-c]吡啶-2(1h)-酮
• 中文别名: 恶唑并[5,4-C]吡啶-2(1H)-酮
• 英文名称: 1H-oxazolo[5,4-c]pyridin-2-one
• 英文别名: Oxazolo[5,4-c]pyridin-2(1H)-one；1H-[1,3]oxazolo[5,4-c]pyridin-2-one
• CAS: 68523-29-5
• 化学式: C₆H₄N₂O₂
• 分子量: 136.11
• InChiKey: YKGGWPMONQFUPR-UHFFFAOYSA-N

物化性质

• 密度：
  1.427±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  噁唑并[5,4-c]吡啶-2(1h)-酮 、 (4-异氰酸丁基)苯 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 以59%的产率得到2-oxo-N-(4-phenylbutyl)oxazolo[5,4-c]pyridine-1-carboxamide
  参考文献：
  名称：

  Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors

  摘要：

  Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.9b02004
• 作为产物：
  描述：

  3-羟基-4-氨基吡啶 、 N,N'-羰基二咪唑 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 以100%的产率得到噁唑并[5,4-c]吡啶-2(1h)-酮
  参考文献：
  名称：

  Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors

  摘要：

  Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.9b02004

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AS INHIBITORS OF HPK1<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE HPK1
  申请人：GUANGDONG NEWOPP BIOPHARMACEUTICALS CO LTD

  公开号：WO2021004547A1

  公开（公告）日：2021-01-14

  This disclosure relates to heterocyclics as inhibitors of HPK1, in particular relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising said compound that useful for treatment of HPK1 mediated diseases and conditions such as cancer. (I)

  这项披露涉及杂环化合物作为HPK1的抑制剂，特别涉及公式I的化合物或其药用盐，以及包含该化合物的药物组合物，用于治疗HPK1介导的疾病和状况，如癌症。 (I)
• [EN] TARGETED PROTEIN DEGRADATION<br/>[FR] DÉGRADATION CIBLÉE DE PROTÉINES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2020132561A1

  公开（公告）日：2020-06-25

  This invention provides pharmaceutical protein degraders and E3 ubiquitin ligase binders for therapeutic applications as described further herein.

  这项发明提供了用于治疗应用的药用蛋白质降解剂和E3泛素连接酶结合物。
• ACETIC ACID AMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY ON ENDOTHELIAL LIPASE
  申请人：Shionogi & Co., Ltd.

  公开号：US20140288302A1

  公开（公告）日：2014-09-25

  A pharmaceutical composition including a compound of formula (I): its pharmaceutically acceptable salt, or a solvate thereof. Ring A is nitrogen-containing hetero ring, Ring A may be substituted with a substituent other than a group represented by formula: —C(R 1 R 2 )—C(═O)—NR 3 R 4 and a group represented by formula: —R 5 , a broken line represents presence or absence of a bond, Z is —NR 6 —, ═N—, —O—, or —S—, R 6 is halogen or substituted or unsubstituted alkyl, R 1 and R 2 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy or substituted or unsubstituted alkyl, R 3 is hydrogen or substituted or unsubstituted alkyl, R 4 is hydrogen or substituted or unsubstituted alkyl, R 3 and R 4 taken together with the adjacent nitrogen atom to which they are attached may form a substituted or unsubstituted ring, R 5 is hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

  一种包括化合物(I)的制药组合物：其药学上可接受的盐或其溶剂合物。环A是含氮杂环，环A可以用除了公式所表示的基团之外的取代基团取代：—C(R1R2)—C(═O)—NR3R4和公式表示的基团：—R5，其中断线表示键的存在或不存在，Z是—NR6—，═N—，—O—或—S—，R6是卤素或取代或未取代的烷基，R1和R2各自独立地是氢、卤素、羟基、氰基、硝基、羧基或取代或未取代的烷基，R3是氢或取代或未取代的烷基，R4是氢或取代或未取代的烷基，R3和R4与它们所连接的相邻氮原子一起可以形成取代或未取代的环，R5是氢、卤素、羟基、氰基、硝基、羧基、取代或未取代的烷基、取代或未取代的烯基或取代或未取代的炔基。
• ACETIC ACID AMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY ON VASCULAR ENDOTHELIAL LIPASE
  申请人：Shionogi & Co., Ltd.

  公开号：EP2351744B1

  公开（公告）日：2015-01-07
• HETEROCYCLEN-DERIVATE ALS SCHÄDLINGSBEKÄMPFUNGSMITTEL
  申请人：Bayer CropScience AG

  公开号：EP3402797B1

  公开（公告）日：2020-02-19