5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] | 1024604-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine]
• 英文别名: 5-Fluoro-1'-[6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl]spiro[3,4-dihydrochromene-2,4'-piperidine]
• CAS: 1024604-46-3
• 化学式: C₂₅H₂₃FN₆O₂
• 分子量: 458.495
• InChiKey: ANTRYADYILUHOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  90.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-chloro-6-(5-pyridin-3-ylmethyl-[1,3,4]oxadiazol-2-yl)pyridazine 、 5-fluorospiro[chromene-2,4'-piperidine] hydrochloride 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 48.0h， 以74%的产率得到5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine]
  参考文献：
  名称：

  Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] analogs

  摘要：

  In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID(50) = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC(50) (mouse)= 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg). (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.044

文献信息

• NICOTINAMIDE RIBOSIDE DERIVATIVES AND THEIR USES
  申请人：Ganapati, Gangadhara

  公开号：EP3642214A2

  公开（公告）日：2020-04-29
• NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES
  申请人：Mitopower LLC

  公开号：EP3897666A2

  公开（公告）日：2021-10-27
• TREATMENT OF AGE-RELATED MACULAR DEGENERATION AND OTHER EYE DISEASES WITH ONE OR MORE THERAPEUTIC AGENTS
  申请人：MacRegen, Inc.

  公开号：US20180296525A1

  公开（公告）日：2018-10-18

  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 certain embodiments, an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic and/or a statin) is used alone to treat or slow the progression of atrophic AMD (including early AMD and intermediate AMD), and/or to prevent or delay the onset of AMD, advanced AMD and/or neovascular AMD. In further embodiments, two or more therapeutic agents (e.g., any combinations of an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector and an anti-angiogenic agent) that target multiple underlying factors of AMD (e.g., formation of lipid-rich deposits, oxidative stress, local inflammation, cell death and neovascularization) are used to treat or slow the progression of atrophic AMD (including non-central GA and central GA) or neovascular AMD (including types 1, 2 and 3 NV), and/or to prevent or delay the onset of AMD, advanced AMD and/or neovascular AMD.
• [EN] NICOTINAMIDE RIBOSIDE DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS DE NICOTINAMIDE RIBOSIDE ET LEURS UTILISATIONS
  申请人：GANAPATI GANGADHARA

  公开号：WO2018236814A2

  公开（公告）日：2018-12-27

  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.
• [EN] NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES<br/>[FR] COMPOSÉS NICOTINYL RIBOSIDE ET LEURS UTILISATIONS
  申请人：MITOPOWER LLC

  公开号：WO2020131578A2

  公开（公告）日：2020-06-25

  The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase intracellular NAD+ levels, and can enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, and other disorders and conditions.