HIGHLY POTENT SUBSTANCE-P ANTAGONISTS SUBSTITUTED WITH BETA-PHENYL-PROLINE OR BETA-BENZYL-PROLINE AT POSITION-10

被引：13

作者：

LAVIELLE, S ^{[1
]}

BRUNISSEN, A ^{[1
]}

CARRUETTE, A ^{[1
]}

GARRET, C ^{[1
]}

CHASSAING, G ^{[1
]}

机构：

[1] RHONE POULENC RORER SA,CTR RECH VITRY ALFORTVILLE,F-94403 VITRY,FRANCE

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1994年 / 258卷 / 03期

关键词：

ANTAGONIST; SUBSTANCE P; SEPTIDE; TACHYKININ NK1 RECEPTOR; PROLINE; BETA-SUBSTITUTED;

D O I：

10.1016/0014-2999(94)90491-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In the guinea-pig ileum tissue, [Pro(9)]substance P, a tachykinin NK1 receptor selective agonist and septide, [pGlu(6),Pro(9)]substance P-(6-11), do not interact with the same receptor as shown by the different inhibitory profiles of GR 72251 and [D-Pro(9),Pro(10),Trp(11)]substance P. Substitution at position 10 of the D-Pro(9)-Pro(10) moiety with bulky N-methylated amino acids increased the antagonist potency for the tachykinin NK1 receptor without affecting that for the 'septide-sensitive receptor'. The incorporation of a trans-beta-L-substituted proline in position 10, for example a benzyl group (beta-benzyl-L-proline), afforded a potent antagonist active in the nanomolar range. For GR 82334, this increase in potency was obtained at the expense of selectivity for tachykinin NK1 and 'septide-sensitive' receptors.

引用

页码：273 / 276

页数：4

共 12 条

[1] SOME QUANTITATIVE USES OF DRUG ANTAGONISTS
ARUNLAKSHANA, O
SCHILD, HO
[J]. BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1959, 14 (01): : 48 - 58
[2] COMPARISON IN DIFFERENT TISSUE PREPARATIONS OF THE INVITRO PHARMACOLOGICAL PROFILE OF RP 67580, A NEW NONPEPTIDE SUBSTANCE-P ANTAGONIST
CARRUETTE, A
MOUSSAOUI, SM
CHAMPION, A
COTTEZ, D
GONIOT, P
GARRET, C
[J]. NEUROPEPTIDES, 1992, 23 (04) : 245 - 250
[3] [PRO(9)]SP AND [PGLU(6), PRO(9)]SP(6-11) INTERACT WITH 2 DIFFERENT RECEPTORS IN THE GUINEA-PIG ILEUM AS DEMONSTRATED WITH NEW SP ANTAGONISTS
CHASSAING, G
LAVIELLE, S
BRUNISSEN, A
CARRUETTE, A
GARRET, C
PETITET, F
SAFFROY, M
BEAUJOUAN, JC
TORRENS, Y
GLOWINSKI, J
[J]. NEUROPEPTIDES, 1992, 23 (02) : 73 - 79
[4] CONFORMATIONALLY CONSTRAINED AMINO-ACIDS - SYNTHESIS AND OPTICAL RESOLUTION OF 3-SUBSTITUTED PROLINE DERIVATIVES
CHUNG, JYL
WASICAK, JT
ARNOLD, WA
MAY, CS
NADZAN, AM
HOLLADAY, MW
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (01) : 270 - 275
[5] HAGAN RM, 1991, BRIT J PHARMACOL, V102, pP168
[6] TRANS-3-NORMAL-PROPYL-L-PROLINE IS A HIGHLY FAVORABLE, CONFORMATIONALLY RESTRICTED REPLACEMENT FOR METHIONINE IN THE C-TERMINAL TETRAPEPTIDE OF CHOLECYSTOKININ - STEREOSELECTIVE SYNTHESIS OF 3-ALLYL-L-PROLINE AND 3-NORMAL-PROPYL-L-PROLINE DERIVATIVES FROM 4-HYDROXY-L-PROLINE
HOLLADAY, MW
LIN, CW
MAY, CS
GARVEY, DS
WITTE, DG
MILLER, TR
WOLFRAM, CAW
NADZAN, AM
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) : 455 - 457
[7] STUDIES IN THE INDOLE SERIES .10. YOHIMBINE .2. THE SYNTHESIS OF YOBYRINE, YOBYRONE AND TETRAHYDROYOBYRINE
JULIAN, PL
KARPEL, WJ
MAGNANI, A
MEYER, EW
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1948, 70 (01) : 180 - 183
[8] LAVIELLE S, 1993, INT J PEPT PROT RES, V42, P270
[9] EVIDENCE FOR THE PRESENCE OF A SEPTIDE-SENSITIVE TACHYKININ RECEPTOR IN THE CIRCULAR MUSCLE OF THE GUINEA-PIG ILEUM
MAGGI, CA
PATACCHINI, R
MEINI, S
GIULIANI, S
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1993, 235 (2-3) : 309 - 311
[10] POSSIBLE EXISTENCE OF A NEW TACHYKININ RECEPTOR SUBTYPE IN THE GUINEA-PIG ILEUM
PETITET, F
SAFFROY, M
TORRENS, Y
LAVIELLE, S
CHASSAING, G
LOEUILLET, D
GLOWINSKI, J
BEAUJOUAN, JC
[J]. PEPTIDES, 1992, 13 (02) : 383 - 388

← 1 2 →