2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers

Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability

“…In the synthetic route 2-chloronicotinic acid (7) was employed as the starting material, which was converted to its ester derivative, ethyl 2-chloronicotinate (8) by using sulphuric acid and ethanol in quantitatively yield 31 (Scheme 1). The ester 8 was subjected to Suzuki coupling by condensation with a variety of substituted boronic acids in the presence of tetrakis(triphenylphosphine)palladium and potassium carbonate in toluene and ethanol-water to afford the intermediates 9a-e, which on subsequent hydrolysis with 2N NaOH solution in ethanol provided 2-phenyl substituted nicotinic acids 10a-e. 34 These key intermediates were utilized in the synthesis of the benzimidazole and benzothiazole mimics of CA4. These intermediates 10a-e were condensed with various substituted o-diaminobenzenes (11) in the presence of polyphosphoric acid under refluxing condition to afford the desired cisrestricted benzimidazole mimics of CA4 (5a-l).…”

Retracted: Synthesis and Cytotoxic Activity of 2‐Anilinopyridine‐3‐Acrylamides as Tubulin Polymerization Inhibitors

“…The preparation of key intermediates (acryl acids 14 a-d) is described in Scheme 1. 2-Chloronicotinic acid (7) was converted into ethyl 2-chloronicotinate (8) by holding at reflux with ethanol and sulfuric acid at 80 8C for 2 h. Treatment of ester 8 with various substituted anilines in ethylene glycol at 160 8C for 8 h yielded substituted ethyl 2-anilinonicotinates 10 a-d. [7] Further, conversion of these esters 10 a-d into Weinreb amides using trimethylaluminum and N,Odimethylhydroxylamine hydrochloride in dichloromethane for 6 h afforded compounds 11 a-d, [20] which were converted into substituted 2-anilinonicotinaldehydes 12 a-d by using diisobutylaluminum hydride (DIBAL-H) in dichloromethane at À78 8C for 30 min. [21] Compounds 12 a-d were treated with ethyl 2-(triphenylphosphoranylidene)acetate in water at 100 8C for 30 min to give 13 a-d, [22] which were hydrolyzed under alkaline conditions to provide the corresponding acids 14 a-d. [7] Preparation of 5 a-h was carried out by coupling the respective 2-anilinonicotinic acids 14 a-e with substituted anilines 15 a-e in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) and hydroxybenzotriazole (HOBt) (Scheme 2, Table 1).…”

“…[6] Based on the E7010 scaffold, we previously designed and synthesized a series of 2-anilinonicotinyl-linked aminobenzothiazoles 3, which showed potent cytotoxicity, cellcycle arrest, and DNA fragmentation. [7] Similarly, 2-anilinonicotinyl sulfonylhydrazide conjugates also showed promising cytotoxic activity; [8] however, 2-anilinonicotinyl-linked oxadiazole derivatives proved to be very good inhibitors of tubulin polymerization. [9] Benzothiazoles are well known to exhibit various biological properties including antimicrobial, anticancer, anti-amyloid, antirheumatic, and antiglutamate activities.…”

“…As part of our ongoing effort to discover novel anticancer agents, we previously reported 2-anilino-linked sulfonylhydrazides, [8] 2-aminobenzothiazole, triazolobenzothiadiazine, [7] and 1,3,4-oxadiazole [9] conjugates as potent anticancer agents. On the basis of these findings, an attempt was made in the present study to incorporate a 2-anilinopyridyl ring in phenyl acrylamides 5 a-h and benzothiazolyl acrylamides 6 a-t.…”

Synthesis and Antimicrobial Evaluation of Some Tricyclic Substituted benzo[h]quinazolines, benzo[h]quinolines and naphthaleno[d]thiazoles

“…Moreover, benzothiazole fused heterocyclic scaffold has been reported to have a relatively variable pharmacological effects such as antimicrobial 34 , anticancer 35,36 , anti-inflammatory 37 , β-2 adrenoceptor agonist and antidepressant activities 38 . Figure 3 depicts some of benzothiazole-containing drugs like; the sulfonamide diuretic ethoxozolmide, the antiviral and immuno-suppressive frentizole, the glutamate receptor antagonist riluzole used in treatment of amyotrophic lateral sclerosis, the anti-diabetic zopolrestat and the amyloid imaging agent thioflavin T 38 .…”