Patent
Substituted quinazolinone compounds
| العنوان: | Substituted quinazolinone compounds |
|---|---|
| Patent Number: | 7,625,909 |
| تاريخ النشر: | December 01, 2009 |
| Appl. No: | 10/850967 |
| Application Filed: | May 21, 2004 |
| مستخلص: | A variety of small molecule, guanidine-containing molecules capable of acting as MC4-R agonists are provided. The compounds are useful in treating MC4-R mediated diseases when administered to subjects. The compounds have the structure IA, IB, and IC where the values of the variables are defined herein. [chemical expression included] |
| Inventors: | Boyce, Rustum S. (San Francisco, CA, US); Aurrecoechea, Natalia (Oakland, CA, US); Chu, Daniel (Santa Clara, CA, US); Smith, Aaron (Union City, CA, US); Conlee, Christopher R. (Morrisville, NC, US); Thompson, Brian D. (Chapel Hill, NC, US); de Armas Kuntz, Judith (Raleigh, NC, US); Musso, David L. (Raleigh, NC, US); Barvian, Kevin K. (Morrisville, NC, US); Thomson, Stephen A. (Durham, NC, US); Swain, William R. (Durham, NC, US); Du, Kien S. (Durham, NC, US); Chauder, Brian A. (Raleigh, NC, US); Speake, Jason D. (Cary, NC, US); Bishop, Michael J. (Chapel Hill, NC, US) |
| Assignees: | Novartis Vaccines and Diagnostics, Inc. (Emeryville, CA, US) |
| Claim: | 1. A compound of formula IA, IB, or IC [chemical expression included] wherein Z 1 is selected from CR 4 or N; Z 2 is selected from CR 5 or N; Z 3 is selected from CR 6 or N; R 1 is selected from substituted or unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, or alkylgroups; R 2 is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, alkylcarbonyl, or arylcarbonyl groups; R 3 is selected from H, or substituted or unsubstituted arylalkyl, heteroarylalkyl, alkoxy, alkylamino, dialkylamino, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, or alkyl groups; R 4 , R 5 , and R 6 are independently selected from H, Cl, I, F, Br, OH, NH 2 , CN, NO 2 , or substituted or unsubstituted alkoxy, alkyl, alkenyl, alkynyl, alkylamino, dialkylamino, cycloalkyl, heterocyclylamino, heteroarylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, or heteroarylaminocarbonyl groups; W is a group of formula IIA; [chemical expression included] R 1′ is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl groups, or heterocyclylalkyl groups; R 2′ is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl groups, or heterocyclylalkyl groups; wherein at least one of R 1′ and R 2′ is a substituted or unsubstituted nonaromatic heterocyclylalkyl group; R 3′ is selected from H, or substituted or unsubstituted aryl, alkyl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, or cycloalkylalkyl groups; R 4′ is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, or heteroarylalkyl groups; or pharmaceutically acceptable salts thereof, stereoisomers thereof, or tautomers thereof. |
| Claim: | 2. The compound of claim 1 , wherein one of R 1′ or R 2′ is a substituted or unsubstituted pyrrolidinylalkyl group. |
| Claim: | 3. The compound of claim 2 , wherein one of R 1′ or R 2′ is a substituted or unsubstituted pyrrolidinylmethyl group or is a substituted or unsubstituted pyrrolidinylethyl group. |
| Claim: | 4. The compound of claim 1 , wherein R 3 is H. |
| Claim: | 5. The compound of claim 1 , wherein Z 1 is a CR 4 group, Z 2 is a CR 5 group, and Z 3 is a CR 6 group. |
| Claim: | 6. The compound of claim 1 , wherein R 3′ is selected from substituted or unsubstituted cycloalkyl, polycyclic cycloalkyl, alkenyl, alkyl, or aryl groups. |
| Claim: | 7. The compound of claim 1 , wherein R 1 is a 2,4-disubstituted phenylethyl group. |
| Claim: | 8. The compound of claim 1 , wherein R 1 is selected from a phenylethyl, 2,4-dichlorophenylethyl, 4-methoxyphenylethyl, 4-phenoxyphenylethyl, 4-bromophenylethyl, 4-methylphenylethyl, 4-chlorophenylethyl, 4-ethylphenylethyl, 2-methoxyphenylethyl, 2-chlorophenylethyl, 2-fluorophenylethyl, 3-methoxyphenylethyl, 3-fluorophenylethyl, thienylethyl, indolylethyl, 4-hydroxyphenylethyl, 3,4-dimethoxyphenylethyl, 2-chloro-4-iodophenylethyl, 2-fluoro-4-methylphenylethyl, 2-fluoro-4-chlorophenylethyl, 2-fluoro-4-bromophenylethyl, 2-fluoro-4-methoxyphenylethyl, 2-trifluoromethyl-4-fluorophenylethyl, 2,4-difluorophenylethyl, 2,4-dimethylphenylethyl, 2,4-dimethoxyphenylethyl, (2-pyridyl)ethyl, (3-pyridyl)ethyl, (4-pyridyl)ethyl, (pyridyl)(hydroxymethyl) ethyl, or (phenyl)(hydroxymethyl)ethyl group. |
| Claim: | 9. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. |
| Claim: | 10. A compound of formula IA, IB, or IC [chemical expression included] wherein Z 1 is CR 4; Z 2 is selected from CR 5 or N; Z 3 is selected from of CR 6 or N; R 1 is selected from substituted or unsubstituted arylalkyl, heteroarylalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, or alkyl groups; R 2 is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, alkylcarbonyl, or arylcarbonyl groups; R 3 is selected from H, or substituted or unsubstituted arylalkyl, heteroarylalkyl, alkoxy, alkylamino, dialkylamino, aryl, heteroaryl, heterocyclyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, alkenyl, alkynyl, or alkyl groups; R 4 , R 5 , and R 6 are independently selected from H, Cl, I, F, Br, OH, NH 2 , CN, NO 2 , or substituted or unsubstituted alkoxy, alkyl, alkenyl, alkynyl, alkylamino, dialkylamino, cycloalkyl, heterocyclylamino, heteroarylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, or heteroarylaminocarbonyl groups; W is a group of formula IIA or IIB; [chemical expression included] wherein R 1′ and R 2′ , together with the nitrogen to which they are bound, join together to form a heterocyclic ring substituted with at least one group selected from substituted or unsubstituted arylalkyl, —C(═O)-alkyl, -alkyl-C(═O)—O-alkyl, —C(═O)—O-alkyl, —C(═O)—NH 2 , —C(═O)—NH(alkyl), —C(═O)—N(alkyl) 2 , dialkylaminoalkyl, alkylaminoalkyl, aminoalkyl, aryl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, or alkylthioalkyl groups; R 3′ is selected from substituted or unsubstituted cycloalkyl, polycyclic cycloalkyl, alkenyl, alkyl, or aryl groups; R 4′ is selected from H, or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclylalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, arylalkyl, or heteroarylalkyl groups; or pharmaceutically acceptable salts thereof, stereoisomers thereof, or tautomers thereof. |
| Claim: | 11. The compound of claim 10 , wherein the heterocyclic ring formed by R 1′ and R 2′ and the nitrogen to which they are bound is a substituted piperazine. |
| Claim: | 12. The compound of claim 11 , wherein the piperazine is substituted with a group selected from a phenylalkyl group, a substituted or unsubstituted phenyl group, an -alkyl-SCH 3 group, an indolylalkyl group, a morpholinylalkyl group, a pyridyl group, a piperidinyl group, or a tetrahydrofuranylalkyl group. |
| Claim: | 13. The compound of claim 10 , wherein the heterocyclic ring formed by R 1′ and R 2′ and the nitrogen to which they are bound is a substituted piperidine. |
| Claim: | 14. The compound of claim 13 , wherein the piperidine is substituted with a group selected from a phenylalkyl group, a substituted or unsubstituted phenyl group, an -alkyl-SCH 3 group, an indolylalkyl group, a morpholinylalkyl group, a pyridyl group, a piperidinyl group, or a tetrahydrofuranylalkyl group. |
| Claim: | 15. The compound of claim 10 , wherein R 3 is H. |
| Claim: | 16. The compound of claim 10 , wherein Z 1 is a CR 4 group, Z 2 is a CR 5 group, and Z 3 is a CR 6 group. |
| Claim: | 17. The compound of claim 10 , wherein R 1 is a 2,4-disubstituted phenylethyl group. |
| Claim: | 18. The compound of claim 10 , wherein R 1 is selected from a phenylethyl, 2,4-dichlorophenylethyl, 4-methoxyphenylethyl, 4-phenoxyphenylethyl, 4-bromophenylethyl, 4-methylphenylethyl, 4-chlorophenylethyl, 4-ethylphenylethyl, 2-methoxyphenylethyl, 2-chlorophenylethyl, 2-fluorophenylethyl, 3-methoxyphenylethyl, 3-fluorophenylethyl, thienylethyl, indolylethyl, 4-hydroxyphenylethyl, 3,4-dimethoxyphenylethyl, 2-chloro-4-iodophenylethyl, 2-fluoro-4-methylphenylethyl, 2-fluoro-4-chlorophenylethyl, 2-fluoro-4-bromophenylethyl, 2-fluoro-4-methoxyphenylethyl, 2-trifluoromethyl-4-fluorophenylethyl, 2,4-difluorophenylethyl, 2,4-dimethylphenylethyl, 2,4-dimethoxyphenylethyl, (2-pyridyl)ethyl, (3-pyridyl)ethyl, (4-pyridyl)ethyl, (pyridyl)(hydroxymethyl) ethyl, or (phenyl)(hydroxymethyl)ethyl group. |
| Claim: | 19. A composition comprising the compound of claim 10 and a pharmaceutically acceptable carrier. |
| Claim: | 20. A method of treating an MC4-R mediated disease, comprising administering to a subject in need thereof, the compound according to claim 1 , wherein the disease is obesity or type II diabetes. |
| Claim: | 21. A method of treating an MC4-R mediated disease, comprising administering to a subject in need thereof, the compound according to claim 10 , wherein the disease is obesity or type II diabetes. |
| Current U.S. Class: | 5142/662 |
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| Assistant Examiner: | Truong, Tamthom N |
| Primary Examiner: | Wilson, James O |
| Attorney, Agent or Firm: | Kathardekar, Vinit Meara, Joseph |
| رقم الانضمام: | edspgr.07625909 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |