Method for preparing microsomal prostaglandin e2 synthase-1 inhibitor

Abstract

The invention discloses a method for preparing microsomal prostaglandin E2 synthase-1 inhibitor. Contains three steps: 1) 5‑iodoisatoic anhydride and 4‑(3‑chlorophenyl) benzylamine hydrochloride to prepare N‑substituted amide; 2) N‑substituted amide and crotyl alcohol to generate 3‑[( 3'-chloro[1,1'-diphenyl]-4-yl)methyl]-2-propyl-6-iodoquinazolone; 3) The product of the previous step reacts Goldberg with o-chlorobenzamide The amination reaction yields the target product. The preparation method has relatively simple steps, avoids the use of alkali and toxic chemical reagents, such as triphenyl phosphite, uses cheap and easy-to-obtain crotyl alcohol as a raw material, automatically transfers hydrogen, does not add alkali in the reaction process, and "one-pot" reaction Complete, the by-product is only water, the reaction atom economy is high, meets the requirements of green chemistry, and has broad development prospects.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a method for preparing microsomal prostaglandin E2 synthase-1 inhibitor. Background technique [0002] Traditional antipyretic and analgesic anti-inflammatory drugs mainly target cyclooxygenase-2 (COX-2), and have a huge market worldwide. Although they have been improved several times, there are still many side effects, and there has been no good effect. substitute. Since the discovery of microsomal prostaglandin synthase-1 (mPGES-1) in 1999, researchers have realized that it may be a new target for antipyretic, analgesic and anti-inflammatory drugs. In the past 10 years since then, a lot of research has been done on its biochemical and pathophysiological properties. However, its pharmaceutical research is still in its infancy, [0003] [0004] Prostaglandin E2 synthase-1, as a class of inhibitors of human microsomal prostaglandin synthase 1, has sh...

AI Technical Summary

Problems solved by technology

The original synthesis method requires 4-step reaction, and the atom economy of the reaction is low, resulting in a very low yield of the reaction

And in the first step reaction, the reaction needs to add an excessive amount of highly toxic triphenyl phosphite, and the reaction will inevitably generate a large amount of by-products (J.Med.Chem.2012,55,3792-3803)

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