Antioxidant compound having anti atherosclerotic effect and preparation thereof

Patent metadata

Field	Value
Publication number	US-9963476-B2
Application number	US-201715443538-A
Country	US
Kind code	B2
Filing date	Feb 27, 2017
Priority date	Feb 19, 2015
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

The present invention relates to an antioxidant compound having anti atherosclerotic effect and preparation thereof. The present invention more particularly relates to the synthesis of TPP+ coupled esculetin (mitochondria-targeted esculetin [Mito-Esc]) followed by the biological evaluation of Mito-Esc for its ability to attenuate Angiotensin-II-induced atherosclerosis in apolipoproteinE knockout (ApoE −/− mice along with the endothelial cell age-delaying effects of Mito-Esc.

First claim

What is claimed is:

1. A process for the preparation of antioxidant compound F,

said process comprising the steps of:
a) providing bromomethyl 9-bromononanoate as compound A and making a solution in dry THF at −75 to −80° C.;
b) providing a solution of t-butyl lithiate as compound B and mixing with THF under nitrogen atmosphere at −75 to −80° C. and adding a solution of LDA to the resulting mixture slowly for 1-2 hr;
c) adding the mixture obtained in step b) to compound A as obtained in step a) at −75 to −80° C. for 1-2 hr to obtain reaction mixture;
d) working up of the reaction mixture as obtained in step c) by quenching and extracting with ethylacetate to obtain organic extracts;
e) washing the organic extracts as obtained in step d) with water and drying over anhydrous Na 2 SO 4 and filtering by known methods to give crude product, compound C as tert-butyl 11-bromo-3-oxoundecanoate;
f) adding benzene-1-2,4-triyl triacetate as compound D to compound C as obtained in step e) in H 2 SO 4 at room temperature for 18-20 hr to obtain the reaction mixture;
g) working up of the reaction mixture as obtained in step f) by diluting with water and extracting with ethyl acetate to obtain organic extracts;
h) washing the organic extracts as obtained in step g with water and drying over anhydrous Na 2 SO 4 and filtering and purifying by known methods to give crude compound E as 4-(8-bromooctyl)-6,7-dihydroxy-2H-chromen-2-one; and
i) mixing of compound E as obtained in step h) in DMF and triphenylphosphine to obtain a reaction mixture and heating the reaction mixture at 150-170° C. for 5-8 hr and further purifying by known methods to obtain the final product compound F as an esculetin analogue.

Assignees

• Council Scient Ind Res

Inventors

• Srigiridhar Kotamraju
• Santosh Karnewar
• Babu Vasamsetti Sathish
• Kumar Togapur Pavan
• Reddy Basi Venkata Subba
• Kumar Jerald Mahesh

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K31/66

  Phosphorus compounds · CPC title

• A61K31/37

  Coumarins, e.g. psoralen · CPC title

• C09B57/02

  Coumarine dyes · CPC title

• C09B69/001

  Dyes containing an onium group attached to the dye skeleton via a bridge · CPC title