1. A compound of formula I
all pharmaceutically acceptable salts and stereoisomers thereof,
wherein:
n is a single bond or a double bond;
R1 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9; provided that R1 is not C1-C6 alkyl when R2 and R3 are C1-C6 alkyl and R6 is a substituted phenyl;
R2 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 is absent when n is a double bond;
R7 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, \u2014COR8, \u2014CO2R8, \u2014CONR8R9 and \u2014S(O)mR8 when n is a single bond;
R8 and R9 independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 4, 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
m is an integer of 1 or 2.
2. The compound according to claim 1, wherein:
R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 is absent;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
n is a double bond.
3. The compound according to claim 2, wherein:
R6 is selected from the group consisting of H , optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units.
4. The compound according to claim 3, wherein:
R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9.
5. The compound according to claim 4, wherein:
R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9.
6. The compound according to claim 5, wherein:
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl.
7. The compound according to claim 1, wherein:
R1 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R2 is selected from the group consisting of optionally substituted heteroaryl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl and optionally substituted heterocyclyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
n is a double bond.
8. The compound according to claim 7, wherein:
R6 is selected from the group consisting of H, methyl, ethyl and isopropyl.
9. The compound according to claim 8, wherein:
R2 is selected from the group consisting of aryl and heteroaryl wherein the aryl or heteroaryl group is optionally substituted with the group consisting of H, alkyl, haloalkyl, halogen, heterocyclyl, aryl, heteroaryl, \u2014OR8, \u2014CO2R8, \u2014CONR8R9, \u2014SO2R8, and \u2014SO2NR8R9.
10. The compound according to claim 9, wherein:
R1 is selected from the group consisting of heterocyclyl, aryl, heteroaryl, aryloxy, heteroaryloxy, \u2014OR8 and \u2014NR8R9 wherein the heterocyclyl, aryl, heteroaryl, aryloxy or heteroaryloxy group is optionally substituted with the group consisting of H, cyano, haloalkyl, alkyl, halogen, heterocyclyl, aryl, heteroaryl, \u2014OR8, \u2014CO2R8, CONR8R9, \u2014SO2R8, and \u2014SO2NR8R9.
11. The compound according to claim 10, wherein:
R3 is selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl, wherein the arylalkyl, heteroarylalkyl or heterocycloalkyl group is optionally substituted with the group consisting of hydrogen, cyano, haloalkyl, alkyl, cycloalkyl, halogen, hydroxyl, amino, \u2014OR8, \u2014NR8NR9, \u2014SO2R8, \u2014SO2NR8R9, heteroaryl, heterocyclyl, and aryl.
12. The compound according to claim 1, wherein:
R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 is selected from the group consisting of H , optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, \u2014CONR8R9, \u2014CO2R8, \u2014COR8 and \u2014SO2R8;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
n is a single bond.
13. The compound according to claim 12, wherein;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units.
14. The compound according to claim 13, wherein;
R7 is selected from the group consisting of H, optionally substituted alkyl, \u2014COR8, \u2014CO2R8, \u2014CONR8R9 and \u2014SO2R8.
15. The compound according to claim 14, wherein:
R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9.
16. The compound according to claim 15, wherein:
R1 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9.
17. The compound according to claim 16, wherein:
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl.
18. The compound according to claim 1, wherein:
R1 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R2 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014OR8 and \u2014NR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 selected from the group consisting of H, \u2014COR8, \u2014CO2R8, \u2014CONR8R9 and \u2014SO2R8;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
n is a single bond.
19. The compound of claim 1 selected from:
20. The compound of claim 1 selected from:
21. The compound of claim 1 selected from;
22. A pharmaceutical composition, comprising: one or more compound of Formula I
all pharmaceutically acceptable salts and stereoisomers thereof,
wherein:
n is a single bond or a double bond;
R1 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9;
R2 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 is absent when n is a double bond;
R7 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, \u2014COR8, \u2014CO2R8, \u2014CONR8R9 and \u2014S(O)mR8 when n is a single bond;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 4, 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
m is an integer of 1 or 2; and
at least one pharmaceutically acceptable diluent or carrier.
23. The pharmaceutical composition according to claim 22, further comprising: at least one other therapeutic agent.
24. A pharmaceutical combination comprising a pharmaceutical composition of claim 22 and a therapeutic agent selected from anti-obesity agents; appetite suppressants; and agents used to treat substance abuse and addictive disorders.
25. A pharmaceutical combination of claim 24 wherein the other therapeutic agent may be administered prior to, simultaneously with, or following the administration of the pharmaceutical composition of claim 22.
26. A pharmaceutical combination of claim 24 wherein the anti-obesity agent is selected from melanocortin receptor (MC4R) agonists; melanin-concentrating hormone receptor (MCHR) antagonists; growth hormone secretagogue receptor (GHSR) antagonists; galanin receptor modulators; orexin antagonists; CCK agonists; GLP-1 agonists and other pPre-proglucagon-derived peptides; NPY1 or NPY5 antagonists; NPY2 and NPY4 modulators; corticotropin releasing factor agonists; histamine receptor-3 (H3) modulators; aP2 inhibitors; PPAR gamma modulators; PPAR delta modulators; acetyl-CoA carboxylase (ACC) inhibitors; 11-\u03b2-HSD-1 inhibitors; adiponectin receptor modulators; beta 3 adrenergic agonists, including AJ9677, L750355 and CP331648 or other known beta 3 agonists; thyroid receptor beta modulator; lipase inhibitors, including orlistat and ATL-962; serotonin receptor agonists, including BVT-933; monoamine reuptake inhibitors or releasing agents, including fenfluramine, dexfenfluramine, fluvoxamine, fluoxetine, paroxetine, sertraline, chlorphentermine, cloforex, clortermine, picilorex, sibutramine, dexamphetamine, phentermine, phenylpropanolamine and mazindol; anorectic agents, including topiramate; ciliary neurotrophic factor, including Axokine; brain-derived neurotrophic factor; leptin and leptin receptor modulators and other cannabinoid-1 receptor antagonists, including SR-141716 and SLV-319.
27. A pharmaceutical combination of claim 24 wherein the agent used to treat substance abuse and addictive disorders is selected from selective serotonin reuptake inhibitors; methadone; buprenorphine; nicotine; and bupropion.
28. A method for treating substance abuse, a dependence disorder, bulimia, obesity or any disease resulting in the patient becoming overweight, comprising: administering to a patient in need of treatment a therapeutically effective amount of a compound according to formula I:
all pharmaceutically acceptable salts and stereoisomers thereof,
wherein:
n is a single bond or a double bond;
R1 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9;
R2 is selected from the group consisting of halogen, cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, \u2014NR8R9, \u2014CO2R8, \u2014CONR8R9, \u2014OR8, \u2014NR8COR9, \u2014NR8CONR8R9, \u2014NR8CO2R9, \u2014OCONR8R9, \u2014NR8S(O)mR9, \u2014NR8S(O)mNR8R9, \u2014NR8S(O)mOR9 and \u2014OS(O)mNR8R9;
R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl;
R6 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl and optionally substituted heteroarylalkyl,
wherein the R6 group has a molecular weight of less than 200 atomic mass units;
R7 is absent when n is a double bond;
R7 is selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, \u2014COR8, \u2014CO2R8, \u2014CONR8R9 and \u2014S(O)mR8 when n is a single bond;
R8 and R9 are independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl;
R8 and R9 taken together can optionally form a 4, 5, 6, or 7 membered optionally substituted heterocyclyl ring or a 5 or 6 membered optionally substituted heteroaryl ring; and
m is an integer of 1 or 2.
29. The method according to claim 28, wherein the obesity is due to genetic or environmental causes, including overeating and bulemia, polycycstic ovary disease, craniopharyngeoma, Prader-Willi Syndrome, Frohlich’s Syndrome, Type II diabetes, growth hormone deficiency, Turner’s Syndrome and other pathological states characterized by reduced metabolic activity or reduced energy expenditure.
30. The method according to claim 28 in which substances of abuse or dependence include alcohol, amphetamines, amphetamine-like substances, caffeine, cannabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, phencyclidine-like compounds, sedative-hypnotics, benzodiazepines, other known or unknown substances, or combinations of the substances of abuse.
31. The method according to claim 30 wherein the substance abuse or dependence may occur without physiological dependence.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-7. (canceled)
8. A method of detecting surface plasmon resonance of a sample containing one or more analytes, comprising:
(1) providing an array comprising:
(a) a substrate comprising a transparent material;
(b) a grating layer adhered to the substrate, the grating layer having a plurality of grating structures fixed to the upper surface of the grating layer; and
(c) a plurality of nanostructures formed on the grating layer such that a local resonance field based on the nanostructures is generated when light is incident to the surface of the grating layer;
(2) contacting the sample with one or more biomolecules attached to the grating layer; and
(3) detecting a shift in the surface plasmon resonance associated with the sample.
9. The method of claim 8, wherein the detecting is performed with a photodetector array.
10. The method of claim 8, wherein the detecting is performed with a charged coupled device (CCD).
11-17. (canceled)
18. A method of detecting surface plasmon resonance of a sample containing one or more analytes, comprising:
(1) providing an array comprising
(a) a substrate comprising a transparent material;
(b) a grating layer adhered to the substrate; and
(c) a plurality of nanostructures formed on a surface of the grating layer such that a local resonance field based on the nanostructures is generated when light is incident to the surface of the grating layer, wherein the nanostructures are spaced
(i) with a first periodic pattern having a size which is greater than the wavelength of the light incident to the surface of the grating layer; and
(ii) with a second periodic pattern having a size which is less than the wavelength of the light incident to the surface of the grating layer;
(2) contacting the sample with one or more biomolecules attached to the grating layer;
(3) positioning the array such that the light is incident to the surface of the grating layer;
(4) capturing the light via a sensor; and
(5) identifying substances in the sample based on a spectrum of the captured light.
19. The method of claim 18, wherein the sensor is a photodetector array.
20. The method of claim 18, wherein the sensor is a charged coupled device (CCD).
21. The method of claim 18, further comprising detecting a shift in the surface plasmon resonance associated with the sample.
22. The method of claim 8, further comprising identifying at least one substance in the sample based on the detecting.