STUDIES ON 1,2,3,6-TETRAHYDROPYRIDINE DERIVATIVES AS POTENTIAL MONOAMINE-OXIDASE INACTIVATORS

被引：32

作者：

HALL, L ^{[1
]}

MURRAY, S ^{[1
]}

CASTAGNOLI, K ^{[1
]}

CASTAGNOLI, N ^{[1
]}

机构：

[1] VIRGINIA POLYTECH INST & STATE UNIV, DEPT CHEM, BLACKSBURG, VA 24061 USA

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 1992年 / 5卷 / 05期

关键词：

D O I：

10.1021/tx00029a006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The Parkinsonian-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and close structural analogs are the only known cyclic tertiary amines with good monoamine oxidase substrate properties. In addition to its excellent substrate properties, MPTP is a mechanism-based inactivator of monoamine oxidase B (MAO-B). In an attempt to exploit the special interactions between this cyclic tertiary allylamine and MAO-B, we have initiated studies to evaluate the enzymatic and biological properties of MPTP analogs bearing functional groups which are known to mediate the metabolism-dependent inactivation of this enzyme. This paper describes the synthesis, enzyme substrate/inhibitor properties, and neurotoxic/neuroprotective properties of 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine, the corresponding acyclic secondary amine (E)-4-cyclopropyl-2-phenyl-2-butene, and 4-cyclopropyl-1-methyl-1,2,3,6-tetrahydropyridine.

引用

页码：625 / 633

页数：9

共 52 条

[1] CDNA CLONING OF HUMAN-LIVER MONOAMINE OXIDASE-A AND OXIDASE-B - MOLECULAR-BASIS OF DIFFERENCES IN ENZYMATIC-PROPERTIES
BACH, AWJ
LAN, NC
JOHNSON, DL
ABELL, CW
BEMBENEK, ME
KWAN, SW
SEEBURG, PH
SHIH, JC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (13) : 4934 - 4938
[2] DEAMINATION OF HORDENINE BY MONOAMINE-OXIDASE AND ITS ACTION ON VASA DEFERENTIA OF THE RAT
BARWELL, CJ
BASMA, AN
LAFI, MAK
LEAKE, LD
[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 1989, 41 (06) : 421 - 423
[3] INCREASED LIFE EXPECTANCY RESULTING FROM ADDITION OF L-DEPRENYL TO MADOPAR TREATMENT IN PARKINSONS-DISEASE - A LONGTERM STUDY
BIRKMAYER, W
KNOLL, J
RIEDERER, P
YOUDIM, MBH
HARS, V
MARTON, J
[J]. JOURNAL OF NEURAL TRANSMISSION, 1985, 64 (02) : 113 - 127
[4] INTERACTION OF MONOAMINE OXIDASE-B WITH ANALOGS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE DERIVED FROM PRODINE-TYPE ANALGESICS
BROSSI, A
GESSNER, WP
FRITZ, RR
BEMBENEK, ME
ABELL, CW
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (04) : 444 - 445
[5] PARGYLINE AND DEPRENYL PREVENT THE NEUROTOXICITY OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) IN MONKEYS
COHEN, G
PASIK, P
COHEN, B
LEIST, A
MYTILINEOU, C
YAHR, MD
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 106 (01) : 209 - 210
[6] BETA-CARBOLINE ANALOGS OF N-METHYL-4-PHENYL-1,2,5,6-TETRA-HYDROPYRIDINE (MPTP) - ENDOGENOUS FACTORS UNDERLYING IDIOPATHIC PARKINSONISM
COLLINS, MA
NEAFSEY, EJ
[J]. NEUROSCIENCE LETTERS, 1985, 55 (02) : 179 - 184
[7] PALLADIUM-CATALYZED COUPLING OF URIDINE TRIFLATE WITH ORGANOSTANNANES
CRISP, GT
FLYNN, BL
[J]. TETRAHEDRON LETTERS, 1990, 31 (09) : 1347 - 1350
[8] INTERACTIONS OF MONOAMINE-OXIDASE WITH SUBSTRATES AND INHIBITORS
DOSTERT, PL
BENEDETTI, MS
TIPTON, KF
[J]. MEDICINAL RESEARCH REVIEWS, 1989, 9 (01) : 45 - 89
[9] SELECTIVE INHIBITORS OF MONOAMINE OXIDASE-A AND OXIDASE-B - BIOCHEMICAL, PHARMACOLOGICAL, AND CLINICAL PROPERTIES
FOWLER, CJ
ROSS, SB
[J]. MEDICINAL RESEARCH REVIEWS, 1984, 4 (03) : 323 - 358
[10] SYNTHESIS AND TOXICITY TOWARD NIGROSTRIATAL DOPAMINE NEURONS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) ANALOGS
FRIES, DS
DEVRIES, J
HAZELHOFF, B
HORN, AS
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (03) : 424 - 427

← 1 2 3 4 5 6 →