Modulation of anxiety through blockade of anandamide hydrolysis

Details Modulation of anxiety through blockade of anandamide hydrolysis Modulation of anxiety through blockade of anandamide hydrolysis

2007-02-13

2007-02-13

Dentz, Bernard (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S329000, C514S447000, C514S471000, C514S472000, C514S484000, C514S490000, C558S417000, C560S115000, C560S133000

Reexamination Certificate

active

10681858

ABSTRACT:
Fatty acid amide hydrolase inhibitors of the Formula:are provided wherein X is NH, CH2, O, or S; Q is O or S; Z is O or N; R is an aromatic moiety selected from the group consisting of substituted or unsubstituted aryl; substituted or unsubstituted biphenylyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted phenyl; substituted or unsubstituted terphenylyl; substituted or unsubstituted cycloalkyl, heteroaryl, or alkyl; and R1and R2are independently selected from the group consisting of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, and substituted or unsubstituted phenyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; with the proviso that if Z is O, one of R1and R2is absent, and that if Z is N, optionally R1and R2may optionally be taken together to form a substituted or unsubstituted N-heterocycle or substituted or unsubstituted heteroaryl with the N atom to which they are each attached. Pharmaceutical compositions comprising the compounds of Formula I and methods of using them to inhibit FAAH and/or treat appetite disorders, glaucoma, pain, insomnia, and neurological and psychological disorders including anxiety disorders, epilepsy, and depression are provided.

REFERENCES:
patent: 3275512 (1966-09-01), Lemin et al.
patent: 3632631 (1972-01-01), Wright et al.
patent: 3880908 (1975-04-01), Fields et al.
patent: 5112859 (1992-05-01), Commons et al.
patent: 5476944 (1995-12-01), Partis et al.
patent: 6096784 (2000-08-01), Lerner et al.
patent: 6251931 (2001-06-01), Boger et al.
patent: 6271015 (2001-08-01), Gilula et al.
patent: 6326156 (2001-12-01), Civelli et al.
patent: 6359010 (2002-03-01), Geracioti, Jr. et al.
patent: 6562846 (2003-05-01), Sit et al.
patent: 6908939 (2005-06-01), Bernardon et al.
patent: 6919358 (2005-07-01), Cheng et al.
patent: 6927228 (2005-08-01), Bernardon et al.
patent: 2002/0187542 (2002-12-01), Gilula et al.
patent: 2002/0188009 (2002-12-01), Sit et al.
patent: 2003/0149082 (2003-08-01), Makriyannis et al.
patent: 2003/0195226 (2003-10-01), Sit et al.
patent: 2005/0137238 (2005-06-01), Bernardon et al.
patent: 4430 600 (1996-02-01), None
patent: 0 193 926 (1986-03-01), None
patent: 0 428 385 (1990-11-01), None
patent: 1 231 212 (2002-08-01), None
patent: 197831 (1987-07-01), None
patent: 8-92167 (1996-04-01), None
patent: WO 96/02524 (1996-02-01), None
patent: WO 98/22458 (1998-05-01), None
patent: WO 98/24396 (1998-06-01), None
patent: WO 02/08185 (2002-01-01), None
patent: WO 02/12210 (2002-02-01), None
patent: WO 02/14267 (2002-02-01), None
patent: WO 03/051841 (2003-06-01), None
patent: WO 03/051842 (2003-06-01), None
patent: WO 03/065989 (2003-08-01), None
U.S. Appl. No. 60/336,289, filed Oct. 31, 2001, Piomelli et al.
Barnett-Norris, J. et al., “Conformational memories and the endocannabinoid binding site at the cannabinoid CB1 receptor” J. Med. Chem. 451:3649-3659 (2002).
Beltramo, M. et al., “Inhibition of anandamide hydrolysis in rat brain tissue by (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one” FEBS Lett. 403:263-267 (1997).
Bisogno, T. et al., “Fatty acid amide hydrolase, an enzyme with many bioactive substrates. possible therapeutic implications” Curr. Pharm. Des. 8:533-547 (2002).
Boger, D. et al., “Exceptionally potent inhibitors of fatty acid amide hydrolase: The enzyme responsible for degradation of endogenous oleamide and anadamide” Proc. Natl. Acad. Sci. USA 97:5044-5049 (2000).
Bracey, M. et al., “Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling” Science 298:1793-1796 (2002).
Cravatt, B. et al., “Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase” Proc. Natl. Acad. Sci. USA 98:9371-9376 (2001).
De Petrocellis, L. et al., “Novel inhibitors of brain, neuronal, and basophilic anandamide amidohydrolase” Biochem. Biophys. Res. Commun. 231:82-88 (1997).
Deutsch, D. et al., “Fatty acid sulfonyl fluorides inhibit anandamide metabolism and bind to the cannabinoid receptor” Biochem. Biophys. Res. Commun. 231:217-221 (1997).
Dinh, T. et al., “Brain monoglyceride lipase participating in endocannabinoid inactivation” Proc. Natl. Acad. Sci. USA 99:10819-10824 (2002).
Kathuria, S. et al., “Modulation of anxiety through blockade of anandamide hydrolysis” Nature Medicine 9(1):76-81 (2003).
Koutek, B. et al., “Inhibitors of arachidonoyl ethanolamide hydrolysis” J. Biol. Chem. 269:22937-22940 (1994).
Lopez-Rodriguez, M., et al., “Design, synthesis, and biological evaluation of new inhibitors of the endocannabinoid uptake: Comparison with effects on fatty acid amidohydrolase” J. Med. Chem. 46:1512-1522 (2003).
Piomelli, D. et al., “The endocannabinoid system as a target for therapeutic drugs” Trends Pharmacol. Sci. 21:218-224 (2000).
Quistad, G. et al., “Fatty acid hydrolase inhibition by neurotoxic organophosphorus pesticides” Toxicology and Applied Pharmacology 173:48-55 (2001).
Reggio, P. et al., “Conformational requirements for endocannabinoid interaction with the cannabinoid receotirs, the anandamide transporter and fatty acid amidohydrolase” Chem. Phys. Lipids 108:15-35 (2000).
Smith, A., “Endocannabinoid System: FAAH better anxiolytics?” Nat. Rev. Drug Discov. 2:92 (2003).
Tarzia, G. et al., “Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors” J. Med. Chem. 46:2352-2360 (2003).
Wendeler, M. et al., “Inhibitors of endocannabinoid degradation: potential therapeutics for neurological disorders” Angew. Chem. Int. Ed. 42:2938-2941 (2003).
Barnes, J.H. et al., “The preparation and pharmacology of some phenolic carbamates and allophanates.” J. Pharmacy Pharmacol., vol. 13, pp. 39-48, (1961).
Bisogno, T. et al., “Fatty acid amide hydrolase, an enzyme with many bioactive substrates. Possible therapeutic implications.” Curr. Pharmaceut. Des., vol. 8, 533-47 (2002).
Brown, L.W. and A.A. Forist, “in vitro and in vivo hydrolysis of salicylanilide N-methylcarbamate and 4-biphenylyl N-methylcarbamate.” J. Pharm. Sci., vol. 61, No., 6, pp. 858-860 (1972).
Kohn, G.K., et al., “Some structural relations of a group of simple alkylphenyl N-methylcarbamates to anticholinestrase activity.” J. Agric. Food Chem., vol. 13, No. 3, pp. 232-235 (1965).
Lopez-Rodriguez, M.L. et al., “Design, synthesis, and biological evaluation of new inhibitors of the endocannabinoid uptake: Comparison with effects of fatty acid amidohydrolase.” J. Med. Chem., vol. 46, No. 8, pp. 1512-1522 (2003).
Quesnelle, C.A. et al., “Directed ortho metalation—cross coupling connections. Nickel (0)-catalyzed cross coupling of aryl triflates with organozinc reagents.” Synlett, vol. 5, No. 5, pp. 349-350 (May 1994).
Smith, A., “FAAH better anxiolytics?” Nature Reviews Drug Discovery vol. 2, p. 92 (2003).
Woods, G.F. et al., “M-diarylbenzenes.” J. Am. Chem. Soc., vol. 73, pp. 3854-3854 (1951).
Woods, G.F., “Preparation and properties of some polyphenyls.” WADC Technical Report, 59-496, pp. 1-170 (1959).
Foster, R.H.K. et al., “Studies in Analgesia: Piperidine Derivatives with Morphine-Like Activity,”J. of Pharmacology., vol. 91, No. 3, pp. 195-209 (1947).
Koutek, B. et al., “Inhibitors of Arachidonoyl Ethanolamide Hydrolysis,”J. of Bio. Chem., Vo. 269, No. 37, pp. 22937-22940 (1994).
Noguchi, J. et al., “Synthetic method of protein analogs. IX. Preparation of polycapramide and poly-3-aminocaproyl-L-phenylalanine,”Nippon Kagaku Zasshi, 76:646-648 (1955).
Wood, E., et al., “A prodrug approach to the design of cRaf1 kinase inhibitors

Affiliated with

Also associated with

Rating

Modulation of anxiety through blockade of anandamide hydrolysis does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Modulation of anxiety through blockade of anandamide hydrolysis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Modulation of anxiety through blockade of anandamide hydrolysis will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3858472