Synthesis of novel tetrahydroisoquinoline bronchodilators

被引：11

作者：

Dalence-Guzman, Maria F. ^{[1
]}

Toftered, Jorgen ^{[1
]}

Oltner, Viveca Thornqvist ^{[1
]}

Wensbo, David ^{[1
]}

Johansson, Martin H. ^{[1
]}

机构：

[1] Respiratorius AB, SE-22643 Lund, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期

关键词：

Asthma; COPD; Bronchodilator; Tetrahydroisoquinoline; Palladium catalyzed cross-coupling; CAPSAZEPINOID BRONCHODILATORS; SMALL AIRWAYS; ASTHMA; RING; SAR; HALIDES; MOIETY; TARGET; POTENT; COPD;

D O I：

10.1016/j.bmcl.2010.07.057

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The synthesis and bronchorelaxing effects of a series of novel tetrahydroisoquinoline amides are described. The compounds were evaluated for their ability to relax LTD4 contracted isolated human small airways ex-vivo. Several compounds demonstrated highly efficacious bronchorelaxing properties. Cinnamide 71 was selected for further studies and constitutes a promising candidate as a novel bronchorelaxing agent for the treatment of pulmonary disorders. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4999 / 5003

页数：5

相关论文

共 29 条

[1]

SYNTHESES AND ADRENERGIC ACTIVITIES OF RING-FLUORINATED EPINEPHRINES [J].

ADEJARE, A ;

GUSOVSKY, F ;

PADGETT, W ;

CREVELING, CR ;

DALY, JW ;

KIRK, KL .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) :1972-1977

[2]

Baroffio Michele, 2008, Ther Adv Respir Dis, V2, P129, DOI 10.1177/1753465808091154

[3]

SAR studies of capsazepinoid bronchodilators 3:: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region) [J].

Berglund, Magnus ;

Dalence-Guzman, Maria F. ;

Skogvall, Staffan ;

Sterner, Olov .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (05) :2529-2540

[4]

SAR studies of capsazepinoid bronchodilators.: Part 2:: Chlorination and catechol replacement in the A-ring [J].

Berglund, Magnus ;

Dalence-Guzman, Maria F. ;

Skogvall, Staffan ;

Sterner, Olov .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (05) :2513-2528

[5]

Small tripeptide surrogates with low nanomolar affinity as potent inhibitors of the botulinum neurotoxin B metallo-proteolytic activity [J].

Blommaert, A ;

Turcaud, S ;

Anne, C ;

Roques, BP .

BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (11) :3055-3062

[6]

CONTRIBUTION CONCERNING PROBLEM OF INTRAMOLECULAR HYDROGEN BONDS IN ORTHO HALOPHENOLS [J].

BOURASSABATAILL.H ;

SAUVAGEAU, P ;

SANDORFY, C .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1963, 41 (09) :2240-&

[7]

The small airways and distal lung compartment in asthma and COPD: a time for reappraisal [J].

Contoli, M. ;

Bousquet, J. ;

Fabbri, L. M. ;

Magnussen, H. ;

Rabe, K. F. ;

Siafakas, N. M. ;

Hamid, Q. ;

Kraft, M. .

ALLERGY, 2010, 65 (02) :141-151

[8]

SAR studies of capsazepinoid bronchodilators.: Part 1:: The importance of the catechol moiety and aspects of the B-ring structure [J].

Dalence-Guzman, Maria F. ;

Berglund, Magnus ;

Skogvall, Staffan ;

Sterner, Olov .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (05) :2499-2512

[9]

EFFECTS OF BRONCHOCONSTRICTORS AND BRONCHODILATORS ON A NOVEL HUMAN SMALL AIRWAY PREPARATION [J].

FINNEY, MJB ;

KARLSSON, JA ;

PERSSON, CGA .

BRITISH JOURNAL OF PHARMACOLOGY, 1985, 85 (01) :29-36

[10]

Practical methylation of aryl halides by Suzuki-Miyaura coupling [J].

Gray, M ;

Andrews, IP ;

Hook, DF ;

Kitteringham, J ;

Voyle, M .

TETRAHEDRON LETTERS, 2000, 41 (32) :6237-6240