Npyy5 antagonists

• US 6,699,891 B1
• Filed: 05/01/2002
• Issued: 03/02/2004
• Est. Priority Date: 11/26/1999
• Status: Expired due to Fees

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Takenaka, Hideyuki, Okada, Tetsuo, Kawanishi, Yasuyuki, Hanasaki, Kohji
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US10/111,981
• Time in Patent Office: 671 Days
• Field of Search: 514/352, 546/309
• US Class Current: 514/352
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/37 Coumarins, e.g. psoralen
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/402 1-aryl substituted, e.g. piretanide
• CPC Class Codes: A61K 31/4035 Isoindoles, e.g. phthalimide
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/4453 : only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/451 : having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 31/495 : having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/4965 : Non-condensed pyrazines
• CPC Class Codes: A61K 31/505 : Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/5375 : 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/63 : Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
• CPC Class Codes: A61K 31/635 : having a heterocyclic ring, e.g. sulfadiazine
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/04 : with a four-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2602/08 : the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 : the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 2602/44 : the bicyclo ring system containing eight carbon atoms
• CPC Class Codes: C07C 2603/18 : Fluorenes; Hydrogenated fluorenes
• CPC Class Codes: C07C 311/06 : to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 311/07 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/08 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/14 : Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07C 311/20 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/21 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/46 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 323/40 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07D 207/09 : Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 207/12 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 207/16 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/48 : with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 209/88 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
• CPC Class Codes: C07D 211/58 : attached in position 4
• CPC Class Codes: C07D 211/62 : attached in position 4
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 215/36 : Sulfur atoms C07D215/24 takes precedence
• CPC Class Codes: C07D 215/38 : Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 217/04 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 219/10 : attached in position 9
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/16 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/56 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 233/68 : Halogen atoms
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 249/08 : 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 277/70 : Sulfur atoms
• CPC Class Codes: C07D 285/06 : 1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
• CPC Class Codes: C07D 295/135 : with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/91 : Dibenzofurans; Hydrogenated dibenzofurans
• CPC Class Codes: C07D 311/16 : substituted in position 7
• CPC Class Codes: C07D 317/66 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/72 : Benzo[c]thiophenes; Hydrogenated benzo[c]thiophenes

Abstract

The present invention provides a pharmaceutical composition for use as an NPY Y5 receptor antagonist comprising a compound of the formula (I):

wherein R¹ is lower alkyl, cycloalkyl or the like,

R² is hydrogen, lower alkyl or the like,

n is 1 or 2,

X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like,

Y is CONR⁷, CSNR⁷, NR⁷CO, NR⁷CS or the like,

Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like and R⁷ is hydrogen or lower alkyl,

prodrug, pharmaceutically acceptable salt or solvate thereof.

Claims

1. A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula (I):

wherein R¹ is optionally substituted lower alkyl, optionally substituted cycloalkyl or optionally substituted aryl,

R² is hydrogen or lower alkyl, and R¹ and R² taken together may form lower alkylene,

n is 1 or 2, R³, R⁴, R⁵ and R⁶ are each independently hydrogen or lower alkyl,

 

is optionally substituted cycloalkylene or optionally substituted bicycloalkylene, and

p and q are each independently 0 or 1,

R⁷ is hydrogen or lower alkyl, and

Z is optionally substituted pyridyl,

prodrug, pharmaceutically acceptable salt or hydrate thereof together with a pharmaceutically acceptable carrier.

2. The pharmaceutical composition claimed in claim 1 wherein R² is hydrogen or lower alkyl.

3. The pharmaceutical composition claimed in claim 1 wherein R¹ is optionally substituted lower alkyl or optionally substituted cycloalkyl, and p and q are 0.

4. The pharmaceutical composition claimed in any one of claims 1 to 3 wherein R¹ is optionally substituted C3 to C10 alkyl.

5. The pharmaceutical composition claimed in any one of claims 1 to 3 which is an anti-obestic agent.

6. The pharmaceutical composition claimed in any one of claims 1 to 3 which is an anorectic agent.

7. A method for treating obesity comprising administering to a subject that is obese an effective dose of the pharmaceutical composition claimed in any one of claims 1 to 3.

8. A method for suppressing food intake comprising administering to a subject that is obese an effective dose of the pharmaceutical composition claimed in any one of claims 1 to 3.

9. A compound of the formula (I);

wherein R¹ is optionally substituted C3 to C10 alkyl or optionally substituted C5 to C6 cycloalkyl and the other symbols are the same as defined in claim 1,

prodrug, pharmaceutically acceptable salt or hydrate thereof.

10. The compound described in claim 9 wherein

is optionally substituted cyclohexylene and p and q are simultaneously 0, prodrug, pharmaceutically acceptable salt or hydrate thereof.