Design and synthesis of m1-selective muscarinic agonists:: (R)-(-)-(Z)-1-azabicyclo[2.2.1]heptan-3-one, O-(3-(3′-methoxyphenyl)-2-propynyl)oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist

被引：30

作者：

Tecle, H ^{[1
]}

Barrett, SD

Lauffer, DJ

Augelli-Szafran, C

Brann, MR

Callahan, MJ

Caprathe, BW

Davis, RE

Doyle, PD

Eubanks, D

Lipiniski, W

Mirzadegan, T

Moos, WH

Moreland, DW

Nelson, CB

Pavia, MR

Raby, C

Schwarz, RD

Spencer, CJ

Thomas, AJ

Jaen, JC

机构：

[1] Parke Davis Pharmaceut Res, Ann Arbor, MI 48106 USA

[2] Receptor Technol Inc, Winooski, VT 05404 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 14期

关键词：

D O I：

10.1021/jm960683m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and SAR of a series of (Z)-(+/-)-1-azabicyclo[2.2. 1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an mi-selective muscarinic agonist. Efficacy and mi selectivity reside in the R enantiomer, (R)-24Z (CI-1017).

引用

收藏

页码：2524 / 2536

页数：13

相关论文

共 56 条

[31]

NABESHIMA T, 1991, J PHARMACOL EXP THER, V257, P562

[32] COMPARISON OF AZABICYCLIC ESTERS AND OXADIAZOLES AS LIGANDS FOR THE MUSCARINIC RECEPTOR [J].

ORLEK, BS ;

BLANEY, FE ;

BROWN, F ;

CLARK, MSG ;

HADLEY, MS ;

HATCHER, J ;

RILEY, GJ ;

ROSENBERG, HE ;

WADSWORTH, HJ ;

WYMAN, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (09) :2726-2735

[33] CORRELATION OF CHOLINERGIC ABNORMALITIES WITH SENILE PLAQUES AND MENTAL TEST-SCORES IN SENILE DEMENTIA [J].

PERRY, EK ;

TOMLINSON, BE ;

BLESSED, G ;

BERGMANN, K ;

GIBSON, PH ;

PERRY, RH .

BRITISH MEDICAL JOURNAL, 1978, 2 (6150) :1457-1459

[34] STEREOISOMERISM AND MUSCARINIC RECEPTOR AGONISTS - SYNTHESIS AND EFFECTS OF THE STEREOISOMERS OF 3-[5-(3-AMINO-1,2,4-OXADIAZOL)YL]-1-AZABICYCLO[2.2.1]HEPTANE [J].

POMBOVILLAR, E ;

WIEDERHOLD, KH ;

MENGOD, G ;

PALACIOS, JM ;

SUPAVILAI, P ;

BODDEKE, HWGM .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1992, 226 (04) :317-325

[35]

RAFFAELE KC, 1991, PSYCHOPHARMACOL BULL, V27, P315

[36] EFFECTS OF ACUTE INFUSION OF THE MUSCARINIC CHOLINERGIC AGONIST ARECOLINE ON VERBAL MEMORY AND VISUOSPATIAL FUNCTION IN DEMENTIA OF THE ALZHEIMER TYPE [J].

RAFFAELE, KC ;

BERARDI, A ;

MORRIS, PP ;

ASTHANA, S ;

HAXBY, JV ;

SCHAPIRO, MB ;

RAPOPORT, SI ;

SONCRANT, TT .

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 1991, 15 (05) :643-648

[37]

RINGDAHL B, 1989, MUSCARINIC RECEPTORS, P151

[38] ESTER BIO-ISOSTERES - SYNTHESIS OF OXADIAZOLYL-1-AZABICYCLO[2.2.1]HEPTANES AS MUSCARINIC AGONISTS [J].

SAUNDERS, J ;

MACLEOD, AM ;

MERCHANT, K ;

SHOWELL, GA ;

SNOW, RJ ;

STREET, LJ ;

BAKER, R .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1988, (24) :1618-1619

[39] CHARACTERIZATION OF MUSCARINIC AGONISTS IN RECOMBINANT CELL-LINES [J].

SCHWARZ, RD ;

DAVIS, RE ;

JAEN, JC ;

SPENCER, CJ ;

TECLE, H ;

THOMAS, AJ .

LIFE SCIENCES, 1993, 52 (5-6) :465-472

[40]

SCHWARZ RD, 1994, ADV ALZ DIS, P224

← 1 2 3 4 5 6 →