Compound, nitric oxide donor prodrug compound as well as preparation method and application of compound and nitric oxide donor prodrug compound

A technology of nitric oxide and compounds, applied in the field of nitric oxide donor prodrug compounds and their preparation, can solve the problems of non-specific hydrolysis of endogenous glycosides, unpredictable physiological consequences, blood pressure drop, etc., to improve the target tropism, avoid non-specific degradation, and improve stability

Active Publication Date: 2021-03-09
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the presence of endogenous galactosidase in normal human tissues and blood, this leads to the non-specific degradation of some prodrugs to release NO, which limits its therapeutic effect and causes side effects such as decreased blood pressure and increased heart rate.
On the other hand, wild-type β-galactosidase is also prone to non-specific hydrolysis of endogenous glycosides, with unpredictable physiological consequences

Method used

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  • Compound, nitric oxide donor prodrug compound as well as preparation method and application of compound and nitric oxide donor prodrug compound
  • Compound, nitric oxide donor prodrug compound as well as preparation method and application of compound and nitric oxide donor prodrug compound
  • Compound, nitric oxide donor prodrug compound as well as preparation method and application of compound and nitric oxide donor prodrug compound

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Experimental program
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Embodiment

[0056] 1. Synthesis of azoenol donor compound (Cel2-NONOate) with cellobioside modification

[0057] (1) Weigh cellobiose (5.00g, 14.6mmol) in a 100mL three-necked flask, under nitrogen protection, add anhydrous pyridine (30mL), use a constant pressure dropping funnel, add dropwise acetic anhydride ( 18 mL), after the addition was complete, the ice bath was removed and stirred at room temperature for 12 h. The reactant disappears. Spin the solvent with an oil pump, add 100mL DCM dichloromethane to dilute, then wash with saturated CuSO 4 (100mL×2), washed with saturated brine (100mL). Anhydrous Na for organic phase 2 SO 4 Dry, filter and spin the filtrate. 7.0 g of white solid powder of fully acetylated cellobiose was obtained, with a yield of 70%.

[0058] (2) Weigh fully acetylated cellobiose (7.0 g, 10.3 mmol) and dissolve it in acetic anhydride (7 mL). 33% HBr / AcOH solution (17.5 mL) was slowly added dropwise with stirring in an ice bath, shielded from light, the ice...

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Abstract

The invention relates to the technical field of biological medicines, in particular to a compound, a nitric oxide donor prodrug compound as well as a preparation method and application of the compoundand the nitric oxide donor prodrug compound. The compound has a structure as shown in a formula I-1, is used for preparing the nitric oxide donor prodrug compound with a structure shown in a formulaI. The preparation method of the compound comprises the following steps: step c), condensing a compound as shown in a formula I-2 with pyrrolidinyl diazonium glycol sodium salt to prepare the compoundas shown in a formula I-1. The preparation method of the nitric oxide donor prodrug compound comprises the following steps: step d), deacetylating the compound of formula I-1 to prepare the compoundof formula I. The nitric oxide donor prodrug compound can controllably release nitric oxide under catalysis of endocellulase, and can controllably release nitric oxide under orthogonal catalysis of endocellulase Cel5A-h38 natural organisms. Therefore, a characteristic that nitric oxide can be controllably released as required is utilized for preparing a medicine capable of controllably releasing nitric oxide.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a compound, a nitric oxide donor prodrug compound and a preparation method and application thereof. Background technique [0002] Nitric oxide (NO) is an important gas signaling molecule in the cardiovascular, immune and central nervous systems, and plays an important role in the treatment of cancer, inflammation and cardiovascular diseases. However, the physiological activity and efficacy of NO are tissue-specific and dose-dependent. Therefore, the development of NO delivery system with targeted and controlled release is currently a hot spot in the field of NO research. [0003] In recent years, due to the rapid development of medicinal chemistry, a variety of NO donor compounds with different structures have been successfully synthesized, including dacarbenols, organic nitrates, nitrous acid thiols, etc. Among them, azoenol compounds (Diazeniumdiolate) are currently the m...

Claims

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Application Information

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IPC IPC(8): C07H13/04C07H1/06C07H1/00A61K33/00A61P17/00A61P9/10
CPCC07H13/04C07H1/00C07H1/06A61K33/00A61P9/10A61P17/00Y02P20/55
Inventor 杨广宇何波汤天辰徐静思史君涵
Owner SHANGHAI JIAO TONG UNIV
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