Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics

被引：14

作者：

Lee, J ^{[1
]}

Kang, MS

Kim, KP

Chung, SJ

Blumberg, PM

Yi, JB

Park, YH

机构：

[1] Seoul Natl Univ, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea

[2] Seoul Natl Univ, Coll Pharm, Lab Pharmaceut, Seoul 151742, South Korea

[3] NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA

[4] Pacific R&D Ctr, Yougin Si 449900, Kyounggi Do, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 04期

关键词：

D O I：

10.1016/S0968-0896(01)00387-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In order to improve the analgesic activity and pharmacokinetics of thioureas 2 and 3, which we previously developed as potent vanilloid receptor (VR) agonists, we prepared and characterized phenolic modifications of them and of their amide surrogates (7, 8). The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50 = 0.96 mug/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1171 / 1179

页数：9

共 20 条

[1] Distinct structure-activity relations for stimulation of Ca-45 uptake and for high affinity binding in cultured rat dorsal root ganglion neurons and dorsal root ganglion membranes [J].

Acs, G ;

Lee, J ;

Marquez, VE ;

Blumberg, PM .

MOLECULAR BRAIN RESEARCH, 1996, 35 (1-2) :173-182

[2]

ACS G, 1995, J NEUROCHEM, V65, P301

[3] Synthesis and evaluation of phorboid 20-homovanillates: Discovery of a class of ligands binding to the vanilloid (Capsaicin) receptor with different degrees of cooperativity [J].

Appendino, G ;

Cravotto, G ;

Palmisano, G ;

Annunziata, R ;

Szallasi, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (16) :3123-3131

[4] Euphorbium: Modern research on its active principle, resiniferatoxin, revives an ancient medicine [J].

Appendino, G ;

Szallasi, A .

LIFE SCIENCES, 1997, 60 (10) :681-696

[5] HYPOTENSIVE AND ANTINOCICEPTIVE EFFECTS OF ETHER-LINKED AND RELATIVELY NON-PUNGENT ANALOGS OF N-NONANOYL VANILLYLAMIDE [J].

CHEN, IJ ;

YANG, JM ;

YEH, JL ;

WU, BN ;

LO, YC ;

CHEN, SJ .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1992, 27 (03) :187-192

[6] 1,1'-THIOCARBONYLDI-2,2'-PYRIDONE - A NEW USEFUL REAGENT FOR FUNCTIONAL-GROUP CONVERSIONS UNDER ESSENTIALLY NEUTRAL CONDITIONS [J].

KIM, S ;

YI, KY .

JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (13) :2613-2615

[7] Capsaicin, protons and heat: new excitement about nociceptors [J].

Kress, M ;

Zeilhofer, HU .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1999, 20 (03) :112-118

[8] N-(3-acyloxy-2-benzylpropyl)-N′-dihydroxytetrahydrobenzazepine and tetrahydroisoquinoline thiourea analogues as vanilloid receptor ligands [J].

Lee, J ;

Szabo, T ;

Gonzalez, AF ;

Welter, JD ;

Blumberg, PM .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (07) :1713-1720

[9] 3-acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid as novel vanilloid receptor agonists [J].

Lee, J ;

Park, SU ;

Kim, JY ;

Kim, JK ;

Lee, J ;

Oh, U ;

Marquez, VE ;

Beheshti, M ;

Wang, QJ ;

Modarres, S ;

Blumberg, PM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (20) :2909-2914

[10] N-(3-acyloxy-2-benzylpropyl)-N′-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics [J].

Lee, J ;

Kim, J ;

Kim, SY ;

Chun, MW ;

Cho, HW ;

Hwang, SW ;

Oh, U ;

Park, YH ;

Marquez, VE ;

Beheshti, M ;

Szabo, T ;

Blumberg, PM .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (01) :19-32

← 1 2 →