N-(3-chlorophenyl)-5-isopropylisoxazole-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-chlorophenyl)-5-isopropylisoxazole-3-carboxamide
• 英文别名: N-(3-chlorophenyl)-5-propan-2-yl-1,2-oxazole-3-carboxamide
• 化学式: C₁₃H₁₃ClN₂O₂
• 分子量: 264.711
• InChiKey: JFZSPOLGILAGQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-异丙基异恶唑-3-羧酸 、 3-氯苯胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 N-(3-chlorophenyl)-5-isopropylisoxazole-3-carboxamide
  参考文献：
  名称：

  Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy

  摘要：

  Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing. Initially, we identified analog 4m that had good in vitro properties but low plasma and brain exposure in a mouse PK experiment due to short plasma stability; this was overcome by reversing the amide bond and changing the heterocycle. Thiazole 27 showed excellent in vitro properties and a promising mouse PK profile, making it suitable for in vivo testing. This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA.

  DOI：

  10.1021/acs.jmedchem.6b01885

文献信息

• SCREENING METHODS FOR SPINAL MUSCULAR ATROPHY
  申请人：Indiana University Research and Technology Corporation

  公开号：US20140193906A1

  公开（公告）日：2014-07-10

  Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.
• COMPOUNDS FOR USE IN SCREENING METHODS FOR SPINAL MUSCULAR ATROPHY
  申请人：Indiana University Research and Technology Corporation

  公开号：US20160052935A1

  公开（公告）日：2016-02-25

  Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.
• US9212209B2
  申请人：——

  公开号：US9212209B2

  公开（公告）日：2015-12-15
• [EN] COMPOUNDS FOR TREATMENT OF SPINAL MUSCULAR ATROPHY<br/>[FR] COMPOSÉS UTILISABLES EN VUE DU TRAITEMENT DE L'AMYOTROPHIE SPINALE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2014012050A2

  公开（公告）日：2014-01-16

  Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.
• [EN] METHODS RELATED TO ACTIVATION OF THE BONE MORPHOGENIC PROTEIN SIGNALING PATHWAY<br/>[FR] MÉTHODES LIÉES À L'ACTIVATION DE LA VOIE DE SIGNALISATION DES PROTÉINES MORPHOGÉNÉTIQUES OSSEUSES
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2019005563A1

  公开（公告）日：2019-01-03

  In one aspect, compounds and compositions that activate BMP signaling and methods of making and using same are disclosed. The disclosed compounds and compositions can be useful for disorders associated with diminished BMP signaling such as, for example, cancer, juvenile polyposis syndrome, hereditary pulmonary arterial hypertension, obesity osteosporosis, and chronic kidney disease. The disclosed compounds and compositions can also be useful in cartilage repair and bone formation. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.