Synthesis and antiallergic activity of some acidic derivatives of 4H-pyrimido[2,1-b]benzazol-4-ones

Abstract

Reactions of 2-aminobenzothiazole, 2-aminobenzoxazole, and 2-amino-1-methylbenzimidazole with dimethyl aminofumarate (DMAF) or diethyl ethoxymethylenemalonate (DEEM) led to 2- or 3-carboxy-4H-pyrimido[2,1-b]-benzazol-4-ones, respectively. Subsequent derivatization of these carboxylic acids gave the corresponding tetrazolylcarboxamides and tetrazoles. These acidic compounds were tested in the rat passive cutaneous anaphylaxis (PCA) assay as potential antiallergic agents. Many of the compounds displayed activity comparable to that shown by disodium cromoglycate (DSCG) when tested by the intraperitoneal route, and some, unlike DSCG, also showed activity when tested orally.

Synthesis of substituted methylidenepyrimidobenzothiazolones as potential cytotoxic agents

“…The gauche The unexpected formation of pyrimidobenzothiazol-2-ones 9 can be rationalized assuming that the addition of 2-aminobenzothiazoles 3 to chloroacrylate 7 proceeds via the imine nitrogen atom and, after the elimination of chloride, substitution products 8 are formed, which undergo spontaneous intramolecular cyclization to yield 9. It is worth mentioning, that previously reported additions of 2-aminobenzothiazoles to 2-alkoxyalkylidenemalonates [5][6][7][8] or ethyl 2-cyano-3,3-bis(methylthio)acrylate 9,10 proceeded always via the amine nitrogen, yielding 3-alkoxycarbonyl or 3-cyanopyrimidobenzothiazol-4-ones, respectively. In turn, addition of 2-aminobenzothiazole 3a to alkyl 2-arylidenemalonates proceeds via the imine nitrogen atom.…”

“…One of such characteristic structural motifs are pyrimidobenzothiazolones, in which a pyrimidine ring is fused with another pharmacophorically active nucleus, benzothiazole, through a nitrogen atom. Synthesis and biological activity of both possible structural arrangements, 4H-pyrimido [ Pyrimidobenzothiazol-4-ones 1 substituted at positions 2, 3 or in benzothiazole moiety were synthesized by condensation of 2-aminobenzothiazoles with diethyl malonates 2 or ethyl acetoacetate 3,4 or in the reaction of 2-aminobenzothiazoles with various Michael acceptors, such as diethyl alkoxymethylidenemalonates, [5][6][7][8] ethyl 2-cyano-3,3-bismethylthioacrylate, 9,10 2-cyano-3-dimethylaminoacrylohydrazides 11 or dimethyl aminofumarate. 6 Pyrimidobenzothiazol-4-ones 1 display interesting biological properties, for example anticancer, [9][10][11] antimicrobial, 2,4,9 antiallergic 6 or antifungal.…”

“…Synthesis and biological activity of both possible structural arrangements, 4H-pyrimido [ Pyrimidobenzothiazol-4-ones 1 substituted at positions 2, 3 or in benzothiazole moiety were synthesized by condensation of 2-aminobenzothiazoles with diethyl malonates 2 or ethyl acetoacetate 3,4 or in the reaction of 2-aminobenzothiazoles with various Michael acceptors, such as diethyl alkoxymethylidenemalonates, [5][6][7][8] ethyl 2-cyano-3,3-bismethylthioacrylate, 9,10 2-cyano-3-dimethylaminoacrylohydrazides 11 or dimethyl aminofumarate. 6 Pyrimidobenzothiazol-4-ones 1 display interesting biological properties, for example anticancer, [9][10][11] antimicrobial, 2,4,9 antiallergic 6 or antifungal. 3,4 Syntheses of 2H-pyrimido [2,1-b] [1,3]benzothiazol-2-ones 2 are usually less effective and were accomplished in a three-component reaction of a substituted benzaldehyde, malonate and 2-aminobenzothiazole 12 or by heating 2-aminobenzothiazoles with propargylic acids, 13 but-2-yn-1,4-diates 14,15 or ethyl cyanoacetate.…”

Simple and Efficient Synthesis of Novel Fused Bicyclic Heterocycles Pyrimido-Thiazine and Their Derivatives

“…This type of compounds shows various biological properties such as antibacterial, antiallergic, anti-inflammatory, antitumor, phsphodiesterase inhibition and antiparkinsonism [1][2][3][4][5][6], many workers have synthesized different 1, 3-thiazines [7,8]. Thiazines are very useful units in the fields of medicinal and pharmaceutical chemistry and have been reported to exhibit a variety of biological activities [9,10].…”

A convenient synthesis of 3-cyano-4-imino-2-methylthio-4H-pyrimido [2,1-b] [1,3] benzothiazole and its reactions with selected nucleophiles

“…A survey of the literature reveals that few references are available on the synthesis and biological activity of heterocycles containing a benzothiazole fused with the pyrimidine ring [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . In our recent publications [16][17][18][19] , we have outlined convenient synthesis of new fused heterocyclic systems like pyrimidobenzothiazoles [16][17] , pyrazolopyrimido benzothiazoles 18 and bezothiazolotriazepines and studies on their biological activities 19 .…”