3-((nitrooxy)methyl)benzoyl chloride | 167370-62-9

• 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: 3-((nitrooxy)methyl)benzoyl chloride
• 英文别名: (3-Carbonochloridoylphenyl)methyl nitrate
• CAS: 167370-62-9
• 化学式: C₈H₆ClNO₄
• 分子量: 215.593
• InChiKey: YNDQKHJKBBDXNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-半胱氨酸乙酯盐酸盐 、 3-((nitrooxy)methyl)benzoyl chloride 在 sodium acetate 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 ethyl (2R)-2-[[3-(nitrooxymethyl)benzoyl]amino]-3-sulfanylpropanoate
  参考文献：
  名称：

  NO-Donors (VII [1]): Synthesis and Cyclooxygenase Inhibitory Properties of N-and S-Nitrooxypivaloyl-cysteine Derivatives of Naproxen — A Novel Type of NO-NSAID

  摘要：

  Nitric oxide (NO) has been reported to subserve many of the same mucosal protection mechanisms as prostaglandins and is sufficient for acute gastroprotection and ulcer healing. In fact, NO-donating NSAID hybrid compounds such as the nitrooxybutyl ester of naproxen show reduced ulcerogenic activity while maintaining anti-inflammatory activity. We introduce two prototypes of novel triple-hybrid compounds consisting of cysteine which is known to enhance the activity of organic nitrates and to reduce nitrate tolerance, an NSAID (naproxen), and an organic nitrate (nitrooxypivaloic acid). L-Cysteine ethyl ester first was N-acylated in a CH2Cl2/H2O two-phase system using the acid chlorides of naproxen or nitrooxypivaloic acid, respectively, and sodium acetate, or alternatively using the DCC-activated nitrooxy acid in absolute CH2Cl2. The N-acylated intermediates were subsequently S-acylated using the acid chlorides or alternatively the carbonyldiimidazole (CDI)-activated acids again. The two naproxon-cysteine-nitrate hybrid prodrugs were screened in vitro for their cyclooxygenase inhibitory properties relative to naproxen. In this screening the N-nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0.1-10 mumol/L against both COX-1 and COX-2, while the S-nitrooxyacylcysteine derivative had only weak activity against COX-1.

  DOI：

  10.1002/1521-4184(200211)335:8<363::aid-ardp363>3.0.co;2-s
• 作为产物：
  描述：

  3-[(nitrooxy)methyl]benzoic acid 在 N,N-二甲基甲酰胺 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 3-((nitrooxy)methyl)benzoyl chloride
  参考文献：
  名称：

  Nitric oxide enhancing diuretic compounds, compositions and methods of use

  摘要：

  该发明描述了包含至少一种增强一氧化氮利尿化合物或其药用盐的新型组合物和试剂盒，以及可选地，至少一种增强一氧化氮化合物和/或至少一种治疗剂的试剂盒。该发明还提供了以下方法：(a)治疗由过多水分和/或电解贮留引起的症状；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)高脂血症。增强一氧化氮利尿化合物包括至少一种增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点与利尿化合物连接，连接通过不能水解的键或基团。

  公开号：

  US20060189603A1

文献信息

• Nitric oxide enhancing diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20060189603A1

  公开（公告）日：2006-08-24

  The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  该发明描述了包含至少一种增强一氧化氮利尿化合物或其药用盐的新型组合物和试剂盒，以及可选地，至少一种增强一氧化氮化合物和/或至少一种治疗剂的试剂盒。该发明还提供了以下方法：(a)治疗由过多水分和/或电解贮留引起的症状；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)高脂血症。增强一氧化氮利尿化合物包括至少一种增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点与利尿化合物连接，连接通过不能水解的键或基团。
• Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20070032533A1

  公开（公告）日：2007-02-08

  The invention describes compositions and kits comprising at least one nitric oxide enhancing angiotensin II antagonist compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing angiotensin II antagonist compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension (o) treating central nervous system disorders; (p) treating metabolic syndrome; and (q) treating hyperlipidemia. The nitric oxide enhancing angiotensin II antagonist compounds comprise at least one nitric oxide enhancing group linked to the angiotensin II antagonist compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  该发明描述了包含至少一种一氧化氮增强的血管紧张素II拮抗剂化合物或其药用盐的组合物和试剂盒，以及包含至少一种一氧化氮增强的血管紧张素II拮抗剂化合物的新型组合物，还可以包含至少一种一氧化氮增强化合物和/或至少一种治疗剂。该发明还提供了用于(a)治疗心血管疾病；(b)治疗肾血管疾病；(c)治疗糖尿病；(d)治疗由氧化应激导致的疾病；(e)治疗内皮功能障碍；(f)治疗由内皮功能障碍引起的疾病；(g)治疗肝硬化；(h)治疗子痫前症；(j)治疗骨质疏松症；(k)治疗肾病；(l)治疗外周血管疾病；(m)治疗门静脉高压症；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；和(q)治疗高脂血症的方法。一氧化氮增强的血管紧张素II拮抗剂化合物包括至少一种一氧化氮增强基团，通过碳、氧和/或氮等一个或多个位点与血管紧张素II拮抗剂化合物连接，连接方式是通过一种不能水解的键或基团。
• NITRIC OXIDE DONATING DIURETIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：GARVEY David S.

  公开号：US20080255101A1

  公开（公告）日：2008-10-16

  The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  这项发明描述了新颖的组合物和试剂盒，包括至少一种增强一氧化氮利尿化合物或其药学上可接受的盐，并且可选地，还包括至少一种增强一氧化氮化合物和/或至少一种治疗剂。该发明还提供了以下方法：(a)治疗由过度水和/或电解质潴留引起的疾病；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗先兆子痫；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)治疗高脂血症。增强一氧化氮利尿化合物包括至少一个增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点连接到利尿化合物上，通过无法水解的键或基团连接。
• NITROOXYDERIVATIVE OF ROCK KINASE INHIBITOR
  申请人：Vivavision (Shanghai) Ltd

  公开号：EP3901156A1

  公开（公告）日：2021-10-27

  The invention provides a small molecule compound of a NO donor, characterized in that the small molecule compound of the NO donor is a compound shown in the following structural formula I or a stereoisomer, a geometric isomer, a tautomer, a racemate, a deuterated isotopic derivative, a hydrate, a solvate, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof; formula I; wherein a ring A is a substituted or unsubstituted heteroaromatic ring; X is selected from (CH2)n, wherein n is selected from 0, 1, 2, or 3; R is a substituent of terminal -O-NO2; R1 is selected from hydrogen, a hydroxyl group, a halogen, an amino group, a cyano group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, or a substituted or unsubstituted heteroalkyl group; R2 and R3 are each independently selected from hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, or an amino protecting group; alternatively, R2 and R3 are connected to each other to form a substituted or unsubstituted cycloheteroalkyl group. The compound has a highly active inhibitory effect on ROCK kinase.

  本发明提供了一种 NO 供体的小分子化合物，其特征在于 NO 供体的小分子化合物是如下结构式 I 所示的化合物或其立体异构体、几何异构体、同分异构体、外消旋体、氘代同位素衍生物、水合物、溶解物、代谢物或药学上可接受的盐或原药； 式 I；其中环 A 是取代或未取代的杂芳香环；X 选自 (CH2)n，其中 n 选自 0、1、2 或 3；R 是末端 -O-NO2 的取代基；R1 选自氢、羟基、卤素、氨基、氰基、取代或未取代的烷基、取代或未取代的烷氧基、取代或未取代的烯基、取代或未取代的炔基、取代或未取代的杂烷基；R2 和 R3 各自独立地选自氢、取代或未取代的烷基、取代或未取代的环烷基或氨基保护基团；或者，R2 和 R3 相互连接形成取代或未取代的环杂烷基。该化合物对 ROCK 激酶具有高活性抑制作用。
• US7396829B2
  申请人：——

  公开号：US7396829B2

  公开（公告）日：2008-07-08