6-[5-(cyclopropylmethyl)-4,5-dihydro-1'H,3H-spiro[1,5-benzoxazepine-2,4'-piperidin]-1'-yl]-N-(2-hydroxy-2-(pyridin-3-yl)ethyl)pyridazine-3-carboxamide | 1298034-40-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-[5-(cyclopropylmethyl)-4,5-dihydro-1'H,3H-spiro[1,5-benzoxazepine-2,4'-piperidin]-1'-yl]-N-(2-hydroxy-2-(pyridin-3-yl)ethyl)pyridazine-3-carboxamide
• 英文别名: 6-[5-(cyclopropylmethyl)spiro[3,4-dihydro-1,5-benzoxazepine-2,4'-piperidine]-1'-yl]-N-(2-hydroxy-2-pyridin-3-ylethyl)pyridazine-3-carboxamide
• CAS: 1298034-40-8
• 化学式: C₂₉H₃₄N₆O₃
• 分子量: 514.627
• InChiKey: WPUFSUFYEYOKFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1'-benzyl-4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4'-piperidine] 在 盐酸 、 5% Pd(II)/C(eggshell) 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 75.0h， 生成 6-[5-(cyclopropylmethyl)-4,5-dihydro-1'H,3H-spiro[1,5-benzoxazepine-2,4'-piperidin]-1'-yl]-N-(2-hydroxy-2-(pyridin-3-yl)ethyl)pyridazine-3-carboxamide
  参考文献：
  名称：

  Discovery of novel SCD1 inhibitors: 5-Alkyl-4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4′-piperidine] analogs

  摘要：

  Expansion of the 6-membered ring and subsequent fine-tuning of the newly obtained 7-membered spiropiperidine structure resulted in the discovery of a series of novel and potent SCD1 inhibitors. Preliminary SAR was explored by modifying an alkyl chain on the azepine nitrogen and resulted in the identification of a highly potent SCD1 inhibitor: 6-[5-(cyclopropylmethyl)-4,5-dihydro-1'H,3H-spiro[1,5-benzoxazepine-2,4'-piperidin]-1'-yl]-N-(2-hydroxy-2-pyridin-3-ylethyl)pyridazine-3-carboxamide (9). Compound 9 exhibited an IC50 value of 0.01 mu M against human SCD1. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.002

文献信息

• NICOTINAMIDE RIBOSIDE DERIVATIVES AND THEIR USES
  申请人：GANAPATI Gangadhara

  公开号：US20180362570A1

  公开（公告）日：2018-12-20

  The disclosure provides derivatives of both the oxidized form and the reduced form of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR, and can increase cellular NAD + levels and improve mitochondrial function. Therefore, the NR and NAR derivatives are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.

  该披露提供了烟酰胺核苷酸（NR）和烟酸核苷酸（NAR）的氧化形式和还原形式的衍生物。与NR和NAR相比，NR和NAR衍生物具有更好的稳定性和生物利用度，并且可以增加细胞NAD+水平并改善线粒体功能。因此，NR和NAR衍生物对治疗线粒体疾病、与线粒体相关的疾病和症状以及其他疾病和症状具有用处。
• [EN] THERAPEUTIC REGIMENS AND METHODS FOR LOWERING BLOOD GLUCOSE AND OR BODY WEIGHT USING GLP-1R AND GCGR BALANCED AGONISTS<br/>[FR] RÉGIMES THÉRAPEUTIQUES ET MÉTHODES POUR FAIRE BAISSER LA GLYCÉMIE ET/OU LE POIDS CORPOREL À L'AIDE D'ANTAGONISTES ÉQUILIBRÉS DU RÉCEPTEUR DU PEPTIDE-1 DE TYPE GLUCAGON ET DU RÉCEPTEUR DU GLUCAGON
  申请人：SPITFIRE PHARMA LLC

  公开号：WO2022125598A1

  公开（公告）日：2022-06-16

  This disclosure relates to the once weekly dosing regimen of a dual GLP-1R and GCGR agonist, formulations, and methods of using the same for treatment of chronic weight management, obesity and/or blood glucose control, including but not limited to dual agonist peptide product of SEQ ID NO. 1.

  本公开涉及一种双重GLP-1R和GCGR激动剂的每周一次剂量方案、配方和使用方法，用于治疗慢性体重管理、肥胖和/或血糖控制，包括但不限于SEQ ID NO. 1的双重激动肽产品。
• Topical delivery of therapeutic agents using cell-penetrating peptides for the treatment of age-related macular degeneration and other eye diseases
  申请人：MacRegen, Inc.

  公开号：US10905770B2

  公开（公告）日：2021-02-02

  The present disclosure provides therapeutic agents for the treatment of age-related macular degeneration (AMD) and other eye disorders. One or more therapeutic agents can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (including non-central GA and central GA) and neovascularization (including types 1, 2 and 3 NV). In some embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector or an anti-angiogenic agent, or any combination thereof. In certain embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic or/and a statin). In some embodiments, the one or more therapeutic agents are mixed with, non-covalently associated with or covalently bonded to a cell-penetrating peptide (CPP), encapsulated in CPP-conjugated nanoparticles, micelles or liposomes, or modified (e.g., stapled, prenylated, lipidated or coupled to a small-molecule α-helix mimic) to acquire membrane-translocating ability. In certain embodiments, the one or more therapeutic agents are administered by eye drop.

  本公开提供了用于治疗老年性黄斑变性（AMD）和其他眼部疾病的治疗剂。一种或多种治疗剂可用于治疗AMD的任何阶段（包括早期、中期和晚期），以及AMD的任何表型，包括地理萎缩（包括非中心性GA和中心性GA）和新生血管（包括1型、2型和3型NV）。在某些实施方案中，一种或多种治疗剂是或包括抗血脂异常剂、抗氧化剂、抗炎剂、补体抑制剂、神经保护剂或抗血管生成剂，或它们的任意组合。在某些实施方案中，一种或多种治疗剂是或包括抗血脂异常剂（例如，载脂蛋白模拟物或/和他汀类药物）。在某些实施方案中，一种或多种治疗剂与细胞穿透肽（CPP）混合、非共价结合或共价键合，包封在CPP共轭的纳米颗粒、胶束或脂质体中，或进行修饰（例如，钉合、前酰化、脂质化或与小分子α-螺旋模拟物偶联）以获得膜转运能力。在某些实施方案中，一种或多种治疗剂通过滴眼液给药。
• NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES
  申请人：Mitopower LLC

  公开号：EP3986420A1

  公开（公告）日：2022-04-27
• GLP-1R AND GCGR AGONISTS, FORMULATIONS, AND METHODS OF USE
  申请人：Spitfire Pharma LLC

  公开号：EP4106796A1

  公开（公告）日：2022-12-28