Novel Hypotensive Agents from Verbesina caracasana. 8. Synthesis and Pharmacology of (3,4-Dimethoxycinnamoyl)-N-agmatine and Synthetic Analogues¹

Abstract

The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some light on the structure-activity relationship of these compounds. Derivatives with the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be responsible for higher hypotensive effects, which were associated with a slight and, in some cases, not dose-related increase of cardiac inotropism, with variable and not significant chronotopic responses, and, only at higher doses, with effects of respiratory depression. Either an increase (to six) or a decrease (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not change blood pressure responses, while slightly increasing the positive inotropic ones. At pharmacological doses, all the studied compounds showed hypotensive and slight positive inotropic effects without relevant chronotropic and respiratory actions.

Amine−Guanidine Switch: A Promising Approach to Improve DNA Binding and Antiproliferative Activities

“…Recrystallization from MeOH and Et 2 O gave 10. Brown solid (yield 56%); mp 271-272°C; 1 H NMR (300 MHz CD 3 OD) δ 5.14 (s, 2H), 8.00-8.31 (m, 9H); 13 24 11.51 (br s, 1H); 13 24.87, 40.21, 46.34, 47.47, 120.88, 122.52, 122.98, 123.16, 124.49, 125.56, 125.68, 126.27, 126.84, 127.88, 128.15, 128.41, 129.66, 130.38, 131.34, 156 (22). To a solution of spermine (343 mg, 1.70 mmol) in DMF (15 mL) was added dropwise a solution of N,N′-bis-Boc-thiourea (235 mg, 0.85 mmol) in DMF (10 mL).…”

“…N 2 ,N 3-Bis(tert-butoxycarbonyl)-N 1 -[4-[(pyrene-1-ylmethyl) amino]butyl] Guanidine (24). 24was obtained from 1-amino-4-[N 2 ,N 3 -bis(tert-butoxycarbonyl)-guanidino]butane 2024 following the general procedure for reductive amination. Light yellow solid (yield 75%); mp > 121°C (dec); R f )…”

Functionalized Ruthenium Complexes: Selective “Turn‐on” Detection of Biologically Relevant Anionic Species

“…4‐(Dimethylamino)pyridine (DMAP), 1‐[3‐(dimethylamino)propyl]‐3‐ethylcarbodiimide (EDCI), N ‐Boc‐ethylenediamine, N ‐Fmoc‐1,6‐diaminohexane hydrobromide, 1,3‐bis( tert ‐butoxycarbonyl)‐2‐methyl‐2‐thiopseudourea, 2‐(2‐aminoethyl)‐1,3‐diBoc‐guanidine, 1‐hexanamine, cis ‐bis(2,2′‐bipyridine)dichlororuthenium(II), and ammonium hexafluorophosphate were also purchased from Aldrich. 2‐(6‐Aminohexyl)‐1,3‐diBoc‐guanidine and 2‐(4‐aminobutyl)‐1,3‐diBoc‐guanidine were synthesized from 1,3‐bis( tert ‐butoxycarbonyl)‐2‐methyl‐2‐thiopseudourea and 1,6‐diaminohexane or 1,4‐diaminobutane, respectively …”

New Cyanopeptide‐Derived Low Molecular Weight Inhibitors of trypsin‐like Serine Proteases

“…Bis-Boc-thiourea (9) was subjected to the nucleophilic attack of 1,4-diaminobutane to give the desired bis-Boc-agmatine (11) [15]. In a second route, S-methylisothiouronium sulfate was acylated by di-tert-butyl dicarbonate in a two-phase-mixture under alkaline conditions to the bis-Boc-substituted derivative 10 [16,17], which reacted with 1,4-diaminobutane to 11 [18].…”