Screening method using the RZR receptor family
AssigneeNovartis AG
InventorsIrmgard Wiesenberg, Martin Missbach
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Abstract
The current invention concerns the use of a receptor from the RZR/ROR receptor family or a functional fragment thereof in a test of a compound for anti-autoimmune, anti-arthritic, anti-tumor, melatonin-like and or melatonin-antagonistic activity and the production of a receptor ligand complex comprising the receptor or a functional fragment thereof and a ligand of the receptor. Also described is a method for testing compounds for said activity (screening for ligands) and the active compounds identified therewith.
Claims23
A method for identifying compounds having anti-autoimmune, anti-arthritic, anti-tumor or melatonin-antagonistic activity comprising the steps of:
- contacting the compound to be tested with a receptor of the RZR/ROR receptor family said receptor being combined with a response element;
- and
- measuring a signal produced by the response element in response to the binding of the compound to the receptor, wherein the compounds are identified.
A method for the modification of the activity of the RZR/ROR receptor family comprising the steps of contacting a melatonin-antagonist or agonist to said receptor family wherein the receptor family activity is modified.
A method for identifying compounds which modify the RZR/ROR receptor family comprising the steps of:
- contacting a compound of formula (1), (2) or (3) ##STR18## wherein R.sub.1 and R.sub.5 are C.sub.3 -C.sub.5 alkyl, C.sub.3 -C.sub.5 alk-2-en-1-yl or C.sub.3 -C.sub.5 alk-2-yn-1-yl;
- and especially allyl, methallyl and propinyl;
- R.sub.2 and R.sub.6 are hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.5 alk-2-en-1-yl, C.sub.3 -C.sub.5 alk-2-yn-1-yl, aryl, aryl lower alkyl, saturated or unsaturated heterocyclyl lower alkyl or lower alkoxy carbonyl lower alkyl;
- R.sub.3 and R.sub.4 are each independently of the other hydrogen, lower alkyl or together form lower alkylidene;
- X is oxo or sulfo;
- R.sub.34 and R.sub.35 are independent of the other hydrogen, methoxy, or fluoro;
- R.sub.35 is hydrogen or methoxycarbonyl,
- R.sub.37 is oxo or sulfo;
- R.sub.38 is hydrogen, C.sub.1 -C.sub.6 alkyl, cyclopropyl, cycloputyl, cyclopentyl, cyclohexyl, C.sub.1 -C.sub.6 alkyl substituted by Br, Cl, F or I, phenyl, C.sub.1 -C.sub.3 alkyl-benzene, substituted or unsubstituted by halogen, indolyl, morpholino, methylmorpholino, amino, amino substituted with C.sub.1 -C.sub.4 alkyl or 1-(2', 3', 4'-trimethoxybenzyl)piperazine-methyl, 2-pyrrolidinone;
- R.sub.39 is hydrogen, methyl or fluoro;
- R.sub.40 is a carbon or nitrogen atom;
- R.sub.41 is a carbon or nitrogen atom or a carbonyl group;
- R.sub.42 is a carbon, nitrogen or sulfur atom or a vinylene group;
- the bond between R.sub.40 and R.sub.41 may be a single or double bond, with the proviso that it is a single bond if R.sub.41 is a carbonyl group or R.sub.40 is a nitrogen atom, with a receptor of the RZR/ROR receptor family, said receptor being combined with a response element;
- and
- measuring a signal produced by the response element in response to the binding of the compound to the receptor, wherein the compounds are identified.
Dependencies are inferred from the claim text.