Structure-activity studies of 4,6-disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives with analgesic and antiinflammatory activities

Abstract

4,6-Disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives showed analgesic and antiinflammatory activities when assayed by the acetic acid writhing test in mice and the carrageenin edema test in rats. To understand how the substituents affect the biological activities, the quantitative structure-activity relationships (QSAR) of 38 compounds were analyzed using the adaptive least-squares method (ALS method). The resulting QSAR suggested that some chemical modifications of 4,6-disubstituted furo[3,2-b]indole derivatives would improve their biological activities. Thus, 15 additional compounds were synthesized to reinforce and confirm the correlation. Among these compounds, particularly 4-(2-ethylhexanoyl)-2-(morpholinocarbonyl)-6-(trifluoromethy l) furo[3,2-b]indole showed pronounced biological activities. This compound gave a pharmacological activity spectrum similar to that of tiaramide but exhibited much higher potency.

Substituted Xanthones as Antimycobacterial Agents

“…For the quantitative description of the biological activity of a classified set of compounds/measurements without exact numerical values like MIC values or binding constants, the Adaptive Least Squares technique of Moriguchi et al is a suitable statistical method [21][22][23] based on an iterative application of the Multiple Linear Regression (MLR) technique with stepwise adaptation of the dependent activity variable. After each ALS iteration [21] the calculated (fitted), scaled activity score of each object is obtained by eq.…”

Synthesis and antibacterial activity of furo[3,2-b]pyrrole derivatives

“…Monge and coworkers 18 have reported the reaction of methyl 2-(2-methoxy-2-oxoethyl)-1H-indole-3-carboxylate with 40% hydrazine hydrate without any solvent for 36h to obtain 2,3,5,6-tetrahydro [1,2]diazepino [5,4-b]indole-1,4-dione, while higher concentration of hydrazine led to the bis-hydrazide. On the other hand Voieduvskyi and coworkers 19 have synthesized a 2-amino-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivative by reaction of an appropriate 1-(2-methoxy-2-oxoethyl)pyrrole-2-carboxylate with 95% hydrazine hydrate in ethanol at 60 o C for 1h.…”

“…Interest in pyrrolo-fused heteroaromatic compounds such as furo-, thieno-and seleno-pyrroles stems mainly from the array of interesting biological activities [1][2][3] or their use as fluorescent dyes. 4 More complex furo-and thieno-pyrroles, such as 6,7-dihydrofuro-and 6,7-dihydrothieno [2',3':4,5] 7 or thieno [3,2-b]pyrrolo [3,2-d]pyridazinones were synthesized and evaluated for their anticancer activity.…”

“…8 Moreover 2,3,5,7-tetrabromobenzofuro [3,2-b]pyrrole has been isolated from Pseudoalteromonas species and showed antimicrobial activity against methicillin-resistant Staphylococcus aureus. 9 Among fused furo [3,2-b]pyrrole derived heterocycles, the synthesis of furo[2,3:4,5]pyrrolo [1,2-d] [1,2,4]triazin-8(7H)-ones has been studied extensively. 7,10,11 However the preparation of appropriate 8-substituted derivatives (in the triazine ring) is limited to 8-hydrazino 7,10 or 8-methylsulfanyl 12 compounds.…”

Synthesis of furo[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine derivatives and their antibacterial activity

“…Furo [3,2-b]pyrroles are isosteres of the indole ring system in which the benzene ring is replaced by the furan ring. Efficient synthetic routes to these heterocycles are of great interest [1][2][3][4] as the furo [3,2-b]pyrrole core has been found in compounds with diverse biological activities [5][6][7] or they are used as the fluorescent dyes 8 . Heterocyclic compounds containing five-and six-membered nitrogen heterocyclic rings have also attracted the attention due to the fact that they exhibit many biological interactions 9,10 .…”