New Pyrroles with Potential Antimycobacterial, Antifungal and Selective COX-2 Inhibiting Activities. Synthetic Methodologies

Abstract

Tuberculosis (TB) and fungal diseases are opportunistic infections that very often complicate the immunological response in HIV-infected individuals [1][2][3]. During our studies on novel antimycobacterial and antifungal agents we synthesized a number of new pyrrole derivatives and among them some proved very active against both fungi and mycobacteria. Some others instead were very selective against mycobacteria only. So we pursued a program aimed at individuating the chemical groups or their association, responsible for the particular activity. Moreover, many other pyrroles we synthesized showed to be very active as COX-2 selective inhibitors. In this review we describe our approaches to the synthesis of the pyrrolic structures studied. N CH 3 N N C H 3 Cl Cl N Cl H NO 2 Cl

Transition Metal‐Catalyzed Synthesis of Monocyclic Five‐Membered Aromatic Heterocycles

“…Like furans, pyrroles represent a very important class of five-membered heterocyclic compounds, broadly found in naturally occurring and biologically active compounds [235][236][237][238][239][240][241][242][243][244][245][246], as well as in artificial materials [242,247,248]. In addition, the pyrrole framework represents some interest as a synthon, allowing access to various essential structures [66,68,[249][250][251][252][253][254].…”

“…In addition, the pyrrole framework represents some interest as a synthon, allowing access to various essential structures [66,68,[249][250][251][252][253][254]. Quite expectedly, a great interest caused by the importance and valuable properties of pyrroles is reflected in a number of excellent reviews on the synthesis of the pyrrole framework appearing recently in the literature [83,237,242,246,248,[255][256][257][258][259][260][261][262][263][264][265]. Apparently, a rational design of general and chemo-and regioselective transition metal-catalyzed methodologies for the pyrrole syntheses [79] still remains a challenging task for many research groups.…”

2‐Aryl‐3‐(1H‐Azol‐1‐yl)‐1H‐Indole Derivatives: A New Class of Antimycobacterial Compounds – Conventional Heating in Comparison with MW‐Assisted Synthesis

“…Using genomic DNA from a strain of Mycobacterium tuberculosis (MT), it was established that a CYP51-like gene encodes a bacterial sterol 14a-demethylase [9] (MT P450 14DM CYP51-like) which acts on 14a-methylsterols and binds azole antifungal drugs [1,10,11]. On the basis of these considerations and because many imidazole and triazole derivatives showed potent antifungal activity associated with good antimycobacterial activity [6,7,12,13], we synthesized a series of 2-aryl-3-(1H-imidazol-1-yl-and 1H-1,2,4-triazol-1-yl)-1H-indole derivatives 3a -j in which the azole moiety is linked at the 3-position of the indole nucleus. The indole moiety is present in only few derivatives already described for their antifungal activity [14 -16] but none of these compounds has been studied to evaluate their potential antimycobacterial activity.…”

Synthetic approaches to bridgehead nitrogen methanesulfonamide derivatives of 3‐amino‐2‐thioxo‐2,3‐dihydrothieno[2,3‐d]pyrimidin‐4(1H)‐ones, potential cox‐2 selective inhibitors

“…These derivatives with functional groups and substituents, present in prototypical leads of above selective inhibitors of COX-2 [3,4], have been obtained through the methods of cyclization reported by Wamhoff [5,6], starting from heteroaromatic -enamino esters. Their COX-2 inhibition activity have been assessed in intact cultured cells [7,8].…”

“…Specifically, 1 H nmr spectra in the region of 11.0-11.6 ppm showed a typical singlet attributable to NH of methanesulfonamide group; the nmr spectra of thio-aryl derivatives exhibited Derivatives 12-15 a,b were assessed as COX-2 inhibitors at 10 μM in a test on culture cells [7,8] that allows the evaluation of the effects of a drug on COX-2 activity after its induction by lipopolysaccharide (LPS) by measuring the production of prostaglandin E 2 (PGE 2 ). Our preliminary results, showing that compounds 12-15a and 13b have an interesting inhibitory activity (Table 1), prompt us to synthesize other derivatives of above heterocyclic system as potential COX-2 inhibitors.…”