Inhibitors of phenylethanolamine N-methyltransferase devoid of α2-adrenoceptor affinity

被引：36

作者：

Grunewald, GL ^{[1
]}

Lu, J ^{[1
]}

Criscione, KR ^{[1
]}

Moro, CO ^{[1
]}

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 23期

关键词：

phenylethanolamine-N-methyltransferase; inhibitor; alpha(2)-adrenoceptor; selectivity; blood-brain barrier;

D O I：

10.1016/j.bmcl.2005.08.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines was synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although their PNMT inhibitory potency decreased compared with corresponding 3-methyl-, 3-hydroxymethyl- or 3-unsubstituted-THIQs, some of them showed good selectivity due to their extremely low a2-adrenoceptor affinity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：5319 / 5323

页数：5

共 30 条

[1] AXELROD J, 1962, J BIOL CHEM, V237, P1657
[2] VAN DER WAALS VOLUMES + RADII
BONDI, A
[J]. JOURNAL OF PHYSICAL CHEMISTRY, 1964, 68 (03) : 441 - +
[3] INHIBITORS OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE AND EPINEPHRINE BIOSYNTHESIS .1. CHLORO-SUBSTITUTED 1,2,3,4-TETRAHYDROISOQUINOLINES
BONDINELL, WE
CHAPIN, FW
GIRARD, GR
KAISER, C
KROG, AJ
PAVLOFF, AM
SCHWARTZ, MS
SILVESTRI, JS
VAIDYA, PD
LAM, BL
WELLMAN, GR
PENDLETON, RG
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1980, 23 (05) : 506 - 511
[4] STERIC EFFECTS - A STUDY OF A RATIONALLY DESIGNED SYSTEM
BOTT, G
FIELD, LD
STERNHELL, S
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (17) : 5618 - 5626
[5] PHARMACOLOGY OF BRAIN EPINEPHRINE NEURONS
FULLER, RW
[J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1982, 22 : 31 - 55
[6] Nanomolar inhibitors of CNS epinephrine biosynthesis:: (R)-(+)-3-fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines as potent and highly selective inhibitors of phenylethanolamine N-methyltransferase
Grunewald, GL
Romero, FA
Criscione, KR
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (06) : 1806 - 1812
[7] 3-Hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display remarkable potency and selectivity
Grunewald, GL
Romero, FA
Criscione, KR
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) : 134 - 140
[8] Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines
Grunewald, GL
Romero, FA
Seim, MR
Criscione, KR
Deupree, JD
Spackman, CC
Bylund, DB
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (04) : 1143 - 1147
[9] Exploring the active site of phenylethanolamine N-methyltransferase:: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors
Grunewald, GL
Romero, FA
Chieu, AD
Fincham, KJ
Bhat, SR
Criscione, KR
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (04) : 1261 - 1273
[10] SYNTHESIS AND EVALUATION OF 3-SUBSTITUTED ANALOGS OF 1,2,3,4-TETRAHYDROISOQUINOLINE AS INHIBITORS OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE
GRUNEWALD, GL
SALL, DJ
MONN, JA
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (04) : 824 - 830

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