New Diosmetin compounds, a process for their prep aration and pharmaceutical compositions containingthem

摘要

#CMT# #/CMT# Diosmetin derivatives (I), are new. #CMT# : #/CMT# Diosmetin derivatives of formula (I), are new. R1-R3 : H or (2S,3S,4R,5S)-3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid moiety. An independent claim is included for the preparation of (I). #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Anticoagulant; Antiinflammatory; Vasotropic; Antidiabetic; Hypotensive; Antiarteriosclerotic; Analgesic; Antianginal; Anorectic; Cerebroprotective. #CMT#MECHANISM OF ACTION : #/CMT# None given. #CMT#USE : #/CMT# (I) are useful for preparing the composition and as drugs for: prevention or treatment of venous disease; treating post-thrombotic syndrome, vascular complications related to diabetes, hypertension, atherosclerosis or inflammation, metabolic syndrome linked to obesity, and vascular complications related to obesity, angina pectoris, arteritis of lower limbs or stroke; and prevention or treatment of chronic venous disease (all claimed). Tests details are described but no results given. #CMT#ADVANTAGE : #/CMT# (I) are non-toxic. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (Claimed): The preparation of (I) comprises: reacting 5,7-dihydroxy-2-(3-hydroxy-4-methoxy-phenyl)-chromen-4-one with methallyl bromide, to give 2-[4-methoxy-3-(2-methyl-allyloxy)-phenyl]-5,7-bis-(2-methyl-allyloxy)-chromen-4-one, which is heated to give (I) (in which R1, R2 and R3 are hydrogen); or reacting other compounds of (I) with 3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester to give (I) (in which R1, R2 and R3 are other than hydrogen), after deprotection of the acid function and alcohol functions of the group (A). #CMT#ADMINISTRATION : #/CMT# Administration of (I) is 0.5-1000 mg/day, orally, parenterally (intravenous, intramuscular or subcutaneous), per- or trans-cutaneously, nasally, rectally, perlingually, ocularly or by respiration. #CMT#SPECIFIC COMPOUNDS : #/CMT# 3 Compounds (I) are specifically claimed i.e. 6,8,2'-tris-(isobut-2-en-1-yl) diosmetin of formula (Ia), (5-hydroxy-2-[3-hydroxy-4-methoxy-2-(isobut-2-en-1-yl)phenyl]-6,8-bis(isobut-2-en-1-yl)-4-oxo-4H-chromen-7-yl) beta-D-glucuronic acid, and 3-[5,7-dihydroxy-6,8-bis(isobut-2-en-1-yl)-4-oxo-4H-chromen-2-yl]6-methoxy-2-(isobut-2-en-1-yl)phenyl beta-D-glucuronic acid. #CMT#[Image]#/CMT# #CMT#EXAMPLE : #/CMT# Diosmetin (30 g) was added to potassium carbonate (69.3 g) and acetone (450 ml). The obtained mixture was heated, then brought to room temperature, and then methallyl bromide (54 g) was added. The reaction mixture was heated to reflux overnight, then brought to room temperature and filtered. The filter cake was rinsed with acetone and the filtrate was evaporated to yield a residue, which was recrystallized from toluene to give 6,8,2'-tris-(isobut-2-en-1-yl) diosmetin.