Journal of the Chemical Society. Perkin transactions I p. 3085 - 3096 (1988)
Update date:2022-09-26
Topics:
Leeson, Paul D.
Emmett, John C.
3'-Heteroarylmethyl analogues (1)-(8) of the natural thyroid hormone 3,3',5-tri-iodo-L-thyronine (T3) were synthesized as potential selective (cardiac-sparing) thyromimetics.The diphenyl ether moiety was constructed by condensation of 3-substituted 4-methoxyphenols with a 3,5-dinitro-L-tyrosine derivative.Synthesis of the key phenols (28)-(32) required the in situ preparation, at low temperatures, of the novel metallated species 2-lithio-5-methoxypyridine (14), 5-lithio-2-methoxypyrimidine (15), 5-lithio-2-methylpyridine (16), 5-bromo-4-lithio-2-methoxypyridine (18) , and 2,6-difluoro-3-lithiopyridine (19), followed by reaction with the benzaldehyde (20).Alternative routes to the pyridazone (36) and thiazolone (37) phenols were developed from the benzyl bromide (33).Structure-activity relationships indicate that selective thyromimetic activity is associated with 2-oxyheteroaren-5-ylmethyl 3'-substitution, as found in the pyridone (1), pyridazinone (2), hydroxypyridine (4) and thiazolone (8).The location of the oxy substituent in the heterocycle is critical for both hormonal activity and for binding to the T3 receptor.
View Morewebsite:http://www.antimex.com
Contact:0086-21-50563169
Address:Room1027,No.Jinyu Road,Pudong
Jiangyin Tenghua Import&Export Co.,Ltd.
Contact:+86-510-86263875
Address:Room 402-B,9 Yanling Road, Jiangyin,Jiangsu, China
Contact:+49-9398-993127
Address:Untertorstr. 27
Jinan Baozhao Pharmaceutical Co., Ltd
Contact:0086-531-86397156 82371858 82371868
Address:Huaneng Road, Jinan, Shandong ,China
Shenzhen ZheYi Chemicals Co.,LTD(Shanghai Branch)
Contact:+86-21-54159691
Address:Room1002,Building No.2, Lane 98 Bixiu Road,Minhang District, Shanghai,China 201100
Doi:10.1021/jo000447q
(2000)Doi:10.1055/s-2004-834825
(2004)Doi:10.1016/S0040-4020(01)96715-8
(1985)Doi:10.1016/j.bmcl.2012.01.028
(2012)Doi:10.1002/chem.200800619
(2008)Doi:10.1021/jo9708699
(1997)
