Recent advances in pharmaceutical applications of solid phase synthesis

Merrifield in 1963 introduced his solid phase technique for synthesis of peptides. The advantage of this approach is that the growing peptide chain is firmly attached to a completely insoluble solid particle and can be washed free of reagents and by-products. It was for reason that the term solid phase peptide synthesis was introduced to describe the new method. This method lends itself to automation and provides a route to the synthesis of many of the higher molecular weight polypeptides and oligonucleotides which have not been accessible by conventional procedures

Synthesis of some novel derivatives of-1,4-benzoxazepine-3,5-diones as Anticonvulsant agents

The present investigation involves the synthesis of 1,4-benzoxazepine-3,5-dione I as a key intermediate for some biological derivatives comprising II and III where the compounds IIa-f were prepared by applying Mannich conditions to I. On the other hand, the compounds III a-g were synthesized by condensation of I with different aromatic aldehydes. The result of preliminary anticonvulsant testing of selected compounds is included

Synthesis of hydroxy ureas as inhibitors of 5-lipoxygenase

A novel series of N-aryl-N-hydroxyurea derivatives [III] was synthesized for possible biological activity as inhibitors of 5-lipoxygenase

Novel piperazinyl-substituted pyrimidines as possible antihypertensive and vasodilators

Three series of piperazinyl-substituted pyrimidine derivatives having the general formulae [II], [V] and [VII] were synthesized. Reaction of 2- amino-4- chloro-6- methylpyrimidine [IA] with a number of 1- aryl- piperazines afforded the corresponding 4- aryl -1- piperazinyl- substituted pyrimidines [II]. The second series was prepared by treating 2- amino -4- [p-carboxy- anilino] -6- methylpyrimidine [III], prepared via reaction of the same substrate [IA] and p-aminobenzioc acid, with thionyl chloride to give the corresponding key intermediate [IV]. The latter was reacted with appropriate 1-aryl-piperazines to furnish the desired products [V]. Additionally, the third series of the target compounds [VII] was prepared by reacting [IA] with 4- aminophenol to give the pyrimidine derivative [VI]. Application of the acid-catalyzed Mannich reaction to the intermediate [VI], using formaldehyde and different 1-aryl- piperazines yielded the corresponding Mannich bases [VII]

Synthesis of novel 1,4-disubstituted piperazines as potential antihypertensive agents

Two series of 1-arylpiperazines linked to nicotinic acid moiety were prepared as potential antihypertensive agents. The first series [compounds II] was prepared via the Mannich reaction of N-nicotinoyl with 4-amino-benzoic acid to give N-nicotinoyl-4-aminobenzoic acid. The latter was treated with thionyl chloride to give the corresponding acid chloride which was reacted with 1-arylpiperazines to give IV. Preliminary screening of the synthesized compounds was performed for their antihypertensive activity

Synthesis of certain 2,6-diamino-4-substituted pyrimidines of pharmaceutical interest

The ongoing interest in the synthesis of certain substituted pyrimidines inducted the author to prepare some substituted amino [II], Mannich bases' [III and IV], semicarbazides [VI] and thiosemicarbazides [VII] having in common the pyrimidine ring system which seems interesting from the pharmaceutical point of view as antileukemic agents. The synthesis of the designed compounds was achieved using 2, 6-diamino-4-chloropyrimidine [I] as the starting compound

Novel 2-mercaptobenzothiazole derivatives, synthesis and antimicrobial activity

A novel series of compounds comprising 2-mercaptobenzothiazole and thiadiazoles, 1, 2, 4-triazoles and 1, 3, 4-oxadiazolines was synthesized. Cyclization of semi-carbazides and thiosemicarbazides [III] by either conc. sulphuric acid or 2N sodium hydroxide yielded the thiadiazoles [IV] and the triazoles [V] respectively. On the other hand, acylated 1, 3, 4-oxadiazolines [VII] were formed by treating N2-arylidenehydrazides [VI] with acetic anhydride. Six compounds were subjected to in vitro testing for antimicrobial activity