%0 Journal Article
%T Synthesis Characterization and Antibacterial, Antifungal Activity of N-(Benzyl Carbamoyl or Carbamothioyl)-2-hydroxy Substituted Benzamide and 2-Benzyl Amino-Substituted Benzoxazines
%A Tyson Belz
%A Saleh Ihmaid
%A Jasim Al-Rawi
%A Steve Petrovski
%J International Journal of Medicinal Chemistry
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/436397
%X New N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13, 20, and 21 were synthesized using sodium bicarbonate and benzyl amine with 2-thioxo-substituted-1,3-benzoxazines 6, 10a, b, 11c, and 12a每n. The 2-thioxo-substituted-1,3-oxazines 6, 10a-b, 11d 12a每n, and 26 were converted to the corresponding 2-methylthio-substituted-1,3-oxazines 14a每l and 24 which were then converted to 2-benzyl amino-substituted-benzoxazines 15a每i by refluxing with benzylamine. Products 15a, b, e, f, and g were also synthesized by boiling the corresponding N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13a, b, f, l, and m in acetic acid. 2-Oxo-substituted-1,3-benzoxazines 22 and 25 were prepared by treating the corresponding 2-methylthio-substituted-1,3-oxazines 14 and 24 with dilute HCl. The N-(benzyl carbamoyl)-2-hydroxy substituted benzamide 23 was synthesized from the reaction of 2-oxo-substituted-1,3-benzoxazine 22 with benzylamine. The new products were characterized using IR, 1H, and 13C NMR in addition to microanalysis. Selected compounds were tested in vitro for antibacterial and antifungi activity and the most active compounds were found to be the 4-(substituted-benzylamino)-2-hydroxy benzoic acids 9a and d (M. chlorophenolicum, MIC 50 and 25ˋ米gmˋLˋ1, resp.), N1, N3-bis (benzyl carbamothioyl)-4,6-dihydroxy-substituted phthalamides 20a and 20c (B. subtilis MIC 12.5, 50ˋ米gmˋLˋ1, resp.) and 21 (M. chlorophenolicum, MIC 50ˋ米gmˋLˋ1). 1. Introduction The search for new antibacterial compounds is a challenging task as bacteria are continuously developing resistance to antimicrobial compounds; however, infections due to such bacterial strains are infrequent although potentially fatal [1每3]. This ongoing problem has resulted in the search for newer, more effective antibacterial compounds [1每3]. Urea, thiourea 3 (X=O or S), and benzo-1,3-oxazine compounds 5 and 6 (Scheme 1) have been shown to possess antibacterial and antifungal properties [4每11]. The benzyl thiourea analogue 3 has been reported to show activity against Gram-positive bacteria [12]. Scheme 1: Previous synthesis of urea or thiourea 3 (X=O or S) and 2-amino benzo1,3-oxazine 5. The N-benzoyl-2-hydroxybenzamides [13] are important pharmacophores for antibacterial activity in which the 2-hydroxy group (hydrogen bonding donor) contributes to the activity, the imide linker (preferred) or urea linker retains activity and free NH is required for high activity. The Topliss method [14] was used in the optimization of salicylic acid derivatives for potential use as antibacterial agents. The employment and
%U http://www.hindawi.com/journals/ijmc/2013/436397/