Benzamide bioisosteres incorporating dihydroheteroazole substructures:: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179)

被引：29

作者：

Einsiedel, J ^{[1
]}

Hübner, H ^{[1
]}

Gmeiner, P ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Emil Fischer Ctr, Dept Med Chem, D-91052 Erlangen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(01)00484-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Conformationally restricted benzamide bioisosteres were investigated when the chiral phenyldihydroimidazole derivative 4e (FAUC 179) showed strong and highly selective dopamine D4 receptor binding (K-ihigh=0.95nM). Mitogenesis experiments indicated partial agonist properties (42%). EPC syntheses of the target compounds of type 4 were performed starting from alpha -amino acids. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2533 / 2536

页数：4

共 34 条

[1]

AGASHARI V, 1995, J NEUROCHEM, V65, P1157

[2] REACTIONS OF AN N-SULFONYLAMINE INNER SALT [J].

ATKINS, GM ;

BURGESS, EM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1968, 90 (17) :4744-&

[3] GENERATION AND CYCLOADDITIONS OF 4,5-DIHYDROOXAZOLE-4-CARBONITRILE AND OXAZOLIDINE-4-CARBONITRILE N-OXIDES [J].

BLAKE, AJ ;

BOYD, EC ;

GOULD, RO ;

PATON, RM .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1994, (19) :2841-2847

[4] SYNTHESIS OF THE POTENT INFLUENZA NEURAMINIDASE INHIBITOR 4-GUANIDINO NEU5AC2EN - X-RAY MOLECULAR-STRUCTURE OF 5-ACETAMIDO-4-AMINO-2,6-ANHYDRO-3,4,5-TRIDEOXY-D-ERYTHRO-L-GLUCO-NONONIC ACID [J].

CHANDLER, M ;

BAMFORD, MJ ;

CONROY, R ;

LAMONT, B ;

PATEL, B ;

PATEL, VK ;

STEEPLES, IP ;

STORER, R ;

WEIR, NG ;

WRIGHT, M ;

WILLIAMSON, C .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1995, (09) :1173-1180

[5]

CRAWHALL JC, 1956, J CHEM SOC, V338, P588

[6]

DJERASSI C, 1947, J AM CHEM SOC, V49, P1688

[7] Phenyloxazoles and phenylthiazoles as benzamide bioisosteres:: Synthesis and dopamine receptor binding profiles [J].

Einsiedel, J ;

Thomas, C ;

Hübner, H ;

Gmeiner, P .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (17) :2041-2044

[8] THE STEREOCHEMISTRY OF AN OXAZOLINE DERIVATIVE OF THREONINE - IMPROVEMENT OF A RECENT THREONINE SYNTHESIS [J].

ELLIOTT, DF .

JOURNAL OF THE CHEMICAL SOCIETY, 1949, (MAR) :589-594

[9] NGD 94-1 as an agonist at human recombinant dopamine D4.4 receptors expressed in HEK293 cells [J].

Gazi, L ;

Sommer, B ;

Nozulak, J ;

Schoeffter, P .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 372 (03) :R9-R10

[10] Receptor density as a factor governing the efficacy of the dopamine D4 receptor ligands, L-745,870 and U-101958 at human recombinant D4.4 receptors expressed in CHO cells [J].

Gazi, L ;

Bobirnac, I ;

Danzeisen, M ;

Schüpbach, E ;

Langenegger, D ;

Sommer, B ;

Hoyer, D ;

Tricklebank, M ;

Schoeffter, P .

BRITISH JOURNAL OF PHARMACOLOGY, 1999, 128 (03) :613-620

← 1 2 3 4 →