230617-67-1Relevant articles and documents
(HETERO)ARYL COMPOUNDS WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
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Page/Page column 75, (2010/11/27)
The present invention relates to (hetero)aryl compounds of general formula (I) wherein the groups and radicals A, B, Q, W, X, Y, Z, R1, R2, R4a, R4b, R5a, R5b, have the meanings given in cl
PYRIDYLOXYMETHYL AND BENZISOXAZOLE AZABICYCLIC DERIVATIVES
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Page 54, (2010/02/08)
An aminomethylpyridyloxymethyl/benzisoxazole substituted azabicyclic compound according to formula (I) a pharmaceutical composition comprising same, and a method of treating one or more CNS or other disorders, including concurrent treatment of disorders such as chizophrenia and depression. Or the (R) or (S) enantiomer thereof, or the cis or trans isomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or of any of the foregoing, wherein m is 0 or 1, Z is wherein R7 is hydrogen or (C1-C3)alkoxy; R8 is hydrogen, hydroxy, or (C1-C3)alkoxy; and R9 is (C1-C3)alkoxy; X is oxygen or NR, wherein R is hydrogen or (C1-C6)alkyl; Y is methylene, wherein n is 0, 1 or 2; or oxygen, nitrogen or sulfur, wherein n is 2, 3 or 4; R1 and R2 are each independently hydrogen, halogen, or a (C1-C6)alkyl, (C1-C6)alkoxy or a (C1-C6)alkoxy(C1-C6)alkyl group, any one of which groups may be unsbustituted or substituted with one or more halogens.
Substituted pyridines as modulators of the mammalian neuronal nicotinic acetylcholine receptor
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, (2008/06/13)
Novel compounds are provided that modulate the neuronal nicotinic acetylcholine receptor (nAChR), particularly the mammalian nAChR (m-nAChR). The compounds are substituted pyridine derivatives such as analogs of 1-[(6-chloro-3-pyridinyl)methyl]-2-imidazolidine and 1-[(6-chloro-3-pyridinyl)methyl]-2-iminothiazole. Methods of using the novel m-nAChR modulators are also provided, including methods of using the compounds as m-nAChR probes and as therapeutic agents to treat mammalian individuals suffering from conditions, disorders or diseases that are responsive to administration of an m-nAChR modulator. The compounds are useful in treating (1) CNS disorders such as Alzheimer's disease, AIDS-associated dementia, Tourette's Syndrome, attention deficit disorder, and attention deficit disorder, (2) inflammation and inflammatory diseases, (3) conditions caused by or associated with smooth muscle contractions, and (4) withdrawal symptoms associated with cessation of chemical substance abuse. The compounds are also useful as non-opiate analgesics, to treat mild, moderate or severe pain. Pharmaceutical formulations containing an m-nAChR modulator of the invention are provided as well.
Novel and potent 6-chloro-3-pyridinyl ligands for the α4β2 neuronal nicotinic acetylcholine receptor
Latli, Bachir,D'Amour, Kevin,Casida, John E.
, p. 2227 - 2234 (2007/10/03)
1-[(6-Chloro-3-pyridinyl)methyl]-2-imidazolidine (1), the N-desnitro metabolite of the major insecticide imidacloprid, is known to have similar potency to that of (-)-nicotine as an inhibitor of [3H](-)-nicotine binding at the rat recombinant α4β2 neuronal nicotinic acetylcholine receptor (nAChR); IC50 values in the present study are 3.8 nM for (-)-nicotine, 6.0 nM for 1, and 155 nM for imidacloprid. Synthesis of new analogues of 1, modified only in the heterocyclic moiety (five-, six-, or seven-membered rings with NH, S, O, and CH2 substituents), gave compounds varying from 4- fold higher potency (2-iminothiazole analogue 10) to > 6000-fold less active than (-)-nicotine. Other potent N-[(6-chloro-3-pyridinyl)methyl] compounds are those in which the heterocyclic imine is replaced with pyrrolidine (19) (IC50 9 nM) or trimethylammonium (22) (IC50 18 nM). A novel conversion of (-)-nicotine to its 6-chloro analogue increased the potency 2-fold. These 6- chloro-3-pyridinyl compounds are of interest as novel nAChR probes and potential metabolites of candidate insecticides.
