24744-59-0Relevant articles and documents
Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists showed enhanced antagonism to capsaicin
Kang, Dong Wook,Kim, Yong Soo,Lim, Kwang Su,Kim, Myeong Seop,Pearce, Larry V.,Pavlyukovets, Vladimir A.,Tao, Andy K.,Lang-Kuhs, Krystle A.,Blumberg, Peter M.,Lee, Jeewoo
experimental part, p. 8092 - 8105 (2011/01/13)
As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3- methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with Ki (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6′-iodononivamide.
4-(3-cyclohexyl-4-hydroxy or-methoxy phenylsulfonyl) 3,5 dibromo phenyl acetic thyromimetic cholesterol-lowering agents
-
, (2008/06/13)
Compounds of general formula (I) STR1 wherein R 1 is (CH 2) n ((CHNR 7 R 8) m C(O)R 9 ; n=1-3; and m=0 or 1;R 3 and R 5 are independently Cl, Br, I, or CH 3 ;R 7 and R 8 are independently H or (C 1 -C 4)alkyl;R 9 is OH, (C 1 -C 4)alkoxy, or NR 7 R 8 ;R 31 is H, Cl, Br, I, (C 1 -C 4)alkyl, (C 4 -C 6)cycloalkyl, (C 1 -C 4)haloalkyl, (C 4 -C 6)halocycloalkyl, or --CH(R 10)Ar where Ar is selected from 5-hydroxypyrid-2-yl, 6-hydroxypyrid-3-yl, 6-hydroxypyridazin-3-yl, 6-methoxypyridazin-3-yl, 6-hydroxypyridazin-3-yl N-oxide, and 6-methoxypyridazin-3-yl N-oxide and R 10 is H or (C 1 -C 4)alkyl;R 41 is OH or a bioprecursor thereof; and the pharmaceutically acceptable salts thereof; are structural analogs of the thyroid hormones T 3 and T 4 and exhibit selective thyromimetic activity. Pharmaceutical compositions of the novel compounds and their use for the treatment of mammalian cholesteremia are provided.