The role of fluorine substitution in the structure-activity relationships (SAR) of classical cannabinoids

被引：6

作者：

Crocker, Peter J.

Mahadevan, Anu

Wiley, Jenny L.

Martin, Billy R.

Razdan, Raj K.

机构：

[1] Organix Inc, Woburn, MA 01801 USA

[2] Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期

关键词：

fluorine substitution; tetrahydrocannabinols; CB1 binding affinity;

D O I：

10.1016/j.bmcl.2007.01.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A facile synthesis of 1-fluoro-1-deoxy-Delta(8)-THC analogs with side chains seven carbons in length, in the alkane/ene/yneseries (6, 5, and 4), was achieved from 1-fluoro-3,5-dimethoxybenzene (1). In vitro studies show that substitution by a fluorine has a significant detrimental effect on CB1 binding which is supported by in vivo testing. The implications of these results on the SAR of classical cannabinoids are discussed. (c) 2007 Published by Elsevier Ltd.

引用

收藏

页码：1504 / 1507

页数：4

相关论文

共 24 条

[1]

ADAMS IB, 1995, J PHARMACOL EXP THER, V273, P1172

[2] AN EFFICIENT PALLADIUM-CATALYZED REACTION OF VINYL AND ARYL HALIDES OR TRIFLATES WITH TERMINAL ALKYNES [J].

ALAMI, M ;

FERRI, F ;

LINSTRUMELLE, G .

TETRAHEDRON LETTERS, 1993, 34 (40) :6403-6406

[3] Unsaturated side chain beta-11-hydroxyhexahydrocannabinol analogs [J].

Busch-Petersen, J ;

Hill, WA ;

Fan, PS ;

Khanolkar, A ;

Xie, XQ ;

Tius, MA ;

Makriyannis, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (19) :3790-3796

[4] PHARMACOLOGICAL EVALUATION OF HALOGENATED DELTA-8-THC ANALOGS [J].

CHARALAMBOUS, A ;

LIN, S ;

MARCINIAK, G ;

BANIJAMALI, A ;

FRIEND, FL ;

COMPTON, DR ;

MARTIN, BR ;

MAKRIYANNIS, A .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1991, 40 (03) :509-512

[5] PET STUDIES IN THE PRIMATE BRAIN AND BIODISTRIBUTION IN MICE USING (-)-5'-18F-DELTA-8-THC [J].

CHARALAMBOUS, A ;

MARCINIAK, G ;

SHIUE, CY ;

DEWEY, SL ;

SCHLYER, DJ ;

WOLF, AP ;

MAKRIYANNIS, A .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1991, 40 (03) :503-507

[6]

COMPTON DR, 1993, J PHARMACOL EXP THER, V265, P218

[7] Development of agonists, partial agonists and antagonists in the Δ8-tetrahydrocannabinol series [J].

Crocker, PJ ;

Saha, B ;

Ryan, WJ ;

Wiley, JL ;

Martin, BR ;

Ross, RA ;

Pertwee, RG ;

Razdan, RK .

TETRAHEDRON, 1999, 55 (49) :13907-13926

[8] Structure activity relationships of tetrahydrocannabinol analogues on human cannabinoid receptors. [J].

Gareau, Y ;

Dufresne, C ;

Gallant, M ;

Rochette, C ;

Sawyer, N ;

Slipetz, DM ;

Tremblay, N ;

Weech, PK ;

Metters, KM ;

Labelle, M .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (02) :189-194

[9] Synthesis and pharmacology of a very potent cannabinoid lacking a phenolic hydroxyl with high affinity for the CB2 receptor [J].

Huffman, JW ;

Yu, S ;

Showalter, V ;

Abood, ME ;

Wiley, JL ;

Compton, DR ;

Martin, BR ;

Bramblett, RD ;

Reggio, PH .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (20) :3875-3877

[10] Selective fluorination in drug design and development: An overview of biochemical rationales [J].

Kirk, Kenneth L. .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2006, 6 (14) :1447-1456