Glucokinase activators

• US 8,034,822 B2
• Filed: 03/08/2007
• Issued: 10/11/2011
• Est. Priority Date: 03/08/2006
• Status: Expired due to Fees

• Current Assignee: Takeda San Diego, Inc. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda San Diego, Inc. (Takeda Pharmaceutical Company Limited)
• Inventors: Kaldor, Stephen W., Cheruvallath, Zacharia, Miura, Joanne, Wolgast, Beverly, Sabat, Mark, Gwaltney, Stephen L., Feng, Jun, Tang, Mingnam, Guntupalli, Prasuna
• Primary Examiner(s): Ward; Paul V.
• Application Number:
  US11/683,955
• Publication Number:
  US 20070213349A1
• Time in Patent Office: 1,678 Days
• Field of Search: 544/283, 514/266.1
• US Class Current: 514/266.1
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds are provided for use with glucokinase that comprise the formula:

wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

Claims

1. A compound comprising:

2. The compound of claim 1 comprising:

3. The compound of claim 1 comprising:

4. The compound of claim 1 comprising:

5. The compound of claim 1 comprising:

6. The compound of claim 1 comprising:

8. The compound of claim 1, wherein R₁ is a substituted or unsubstituted heteroaryl.

9. The compound of claim 1, wherein R₁ is selected from the group consisting of thiazolyl and pyridyl;

each substituted or unsubstituted.

10. The compound of claim 1, wherein R₁ is selected from the group consisting of thiazol-2-yl;

2-pyridyl;

5-methyl-thiazol-2-yl;

6-methyl-pyrid-2-yl;

4-methyl-pyrid-2-yl;

5-bromo-6-methyl-pyrid-2-yl;

5-phenyl-pyrid-2-yl;

benzothiazol-2-yl;

a nictoinic acid methyl ester; and

5-bromo-pyrid-2-yl.

11. The compound of claim 1, wherein R₁ comprises:

12. The compound of claim 1, wherein R₁ is selected from the group consisting of thiazolyl and pyridinyl, each substituted or unsubstituted.

13. The compound of claim 1, wherein R₃ is selected from the group consisting of hexylmethyl;

benzyl;

imidazol-4-ylmethyl and (tetrahydro-2H-pyran-4-yl)methyl.

14. The compound of claim 1, wherein R₆ is selected from the group consisting of hydrogen and a substituted or unsubstituted (C_1-10)alkyl.

15. The compound of claim 1, wherein R₆ is methyl.

16. The compound of claim 1, wherein R₇ is selected from the group consisting of hydrogen and a substituted or unsubstituted (C_1-10)alkyl.

17. The compound of claim 1, wherein R₇ is methyl.

18. The compound of claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt.

19. A pharmaceutical composition comprising as an active ingredient a compound according to claim 1.

7. A compound selected from the group consisting of:

(S)-2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-4-methylpentanoic acid;

(S)-2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-4-methyl-N-(thiazol-2-yl)pentanamide;

(S)-4-methyl-2-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)pentanoic acid;

(S)-4-methyl-2-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(thiazol-2-yl)pentanamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-phenyl-N-(thiazol-2-yl)acetamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-phenyl-N-(pyridin-2-yl)propanamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)-3-phenylpropanamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-phenyl-N-(thiazol-2-yl)propanamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(1H-imidazol-4-yl)-N-(5-methylthiazol-2-yl)propanamide;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(1H-imidazol-4-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl-N-(pyridin-2-yl)propanamide;

3-cyclohexyl-2-(2,4-dioxo-1,2-dihydroquinazolin-3 (4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(7-(methylsulfonyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H) yl)-N-(5-methylthiazol-2-yl)propanamide;

(S)-methyl 3-cyclohexyl-2-(4-oxoquinazolin-3(4H)-yl)propanoate;

(S)-3-cyclohexyl-2-(4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propan-amide;

(S)-3-cyclohexyl-N-(5-methylthiazol-2-yl)-2-(4-oxoquinazolin-3(4H)-yl)propanamide;

(S)-cyclohexyl-2-(4-oxoquinazolin-3(4H)-yl)-N-(pyridin-2-yl)propanamide;

(R)-3-cyclohexyl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

(R)-3-cyclohexyl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)-N-(pyridin-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(5-(hydroxymethyl)thiazol-2-yl)propanamide;

methyl 2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(1-methyl-1H-imidazol-2-yl)propanoate;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(1-methyl-1H-imidazol-2-yl)propanoic acid;

2-(2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(1-methyl-1H-imidazol-2-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)propanamide;

N-(benzo[d]thiazol-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(pyridin-2-yl)propanamide;

2-(6-chloro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-cyclohexyl-N-(thiazol-2-yl)propanamide;

N-(5-chlorothiazol-2-yl)-3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propanamide;

2-(6-chloro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-cyclohexyl-N-(thiazol-2-yl)propanamide;

6-(3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propanamido)picolinic acid;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(1-methyl-1H-pyrazol-3-yl)propanamide;

2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(tetrahydro-2H-pyran-4-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)propanamide;

2-(6-Chloro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-3-(tetrahydro-pyran-4-yl)-N-thiazol-2-yl-propionamide;

2-(6-Methanesulfonyl-1,3-dioxo-3,4-dihydro-1H-isoquinolin-2-yl)-3-(tetrahydro-pyran-4-yl)-N-thiazol-2-yl-propionamide;

2-(6-Fluoro-4-oxo-4H-quinazolin-3-yl)-3-(tetrahydro-pyran-4-yl)-N-thiazol-2-yl-propionamide;

2-(6-Chloro-4-oxo-4H-quinazolin-3-yl)-N-(5-chloro-thiazol-2-yl)-3-cyclohexyl-propionamide;

2-(6-Chloro-4-oxo-4H-quinazolin-3-yl)-3-cyclohexyl-N-(5-methyl-[1,3,4]oxadiazol-2-yl)-propionamide;

2-(6-Chloro-4-oxo-4H-quinazolin-3-yl)-3-cyclohexyl-N-(5-methyl-[1,3,4]thiadiazol-2-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxo-4H-quinazolin-3-yl)-propionamide;

N-(5-chlorothiazol-2-yl)-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

N-(5-Chloro-thiazol-2-yl)-2-(6-fluoro-4-oxo-4H-quinazolin-3-yl)-3-(tetrahydro-pyran-4-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclopentyl-2-(6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclopentyl-2-(6-fluoro-4-oxo-4H-quinazolin-3-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(7-methanesulfonyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-Cyclohexyl-2-(6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-N-(5-fluoro-thiazol-2-yl)-propionamide;

3-Cyclopentyl-2-(6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-N-(5-fluoro-thiazol-2-yl)-propionamide;

N-(5-Chloro-thiazol-2-yl)-3-cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-pyridin-2-yl-propionamide;

3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-(5-methyl-thiazol-2-yl)-propionamide;

3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-2-thioxo-1,4-dihydro-2H-quinazolin-3-yl)-N-thiazol-2-yl-propionamide;

3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-2-thioxo-1,4-dihydro-2H-quinazolin-3-yl)-N-pyridin-2-yl-propionamide;

6-[3-Cyclohexyl-2-(7-methanesulfonyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-propionylamino]-nicotinic acid;

6-[3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinic acid;

3-Cyclohexyl-2-(6-fluoro-4-oxo-4H-quinazolin-3-yl)-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide;

3-cyclohexyl-N-(5-(hydroxymethyl)pyridin-2-yl)-2-(7-(methylsulfonyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propanamide;

3-Cyclohexyl-2-(6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide;

3-Cyclohexyl-N-(5-hydroxymethyl-pyridin-2-yl)-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-Cyclohexyl-N-(5-fluoro-pyridin-2-yl)-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-Cyclohexyl-2-(7-ethanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-(5-fluoro-pyridin-2-yl)-propionamide;

N-(5-Chloro-pyridin-2-yl)-3-cyclohexyl-2-(7-ethanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-Cyclohexyl-2-(7-ethanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-(5-hydroxymethyl-thiazol-2-yl)-propionamide;

3-Cyclohexyl-2-(7-cyclopropanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-(5-fluoro-pyridin-2-yl)-propionamide;

N-(5-Chloro-pyridin-2-yl)-3-cyclohexyl-2-(7-cyclopropanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

3-{6-[3-Cyclohexyl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-pyridin-3-yl}-propionic acid ethyl ester;

N-(5-Chloro-pyridin-2-yl)-3-(2,6-difluoro-phenyl)-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

methyl 6-(3-cyclohexyl-2-(7-(cyclopropylsulfonyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propanamido)nicotinate;

N-(5-Chloro-pyridin-2-yl)-3-cyclohexyl-2-(6-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

6-[3-Cyclohexyl-2-(7-cyclopentanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinamide;

6-[3-Cyclohexyl-2-(7-ethanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinamide;

N-(5-Chloro-pyridin-2-yl)-3-cyclohexyl-2-(6-methanesulfonyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-propionamide;

6-[3-Cyclohexyl-2-(7-cyclopentanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinic acid methyl ester;

N-(5-Chloro-pyridin-2-yl)-3-cyclohexyl-2-[4-oxo-6-(propane-2-sulfonyl)-4H-quinazolin-3-yl]-propionamide;

6-[2-(7-Methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-3-(tetrahydro-furan-2-yl)-propionylamino]-nicotinic acid methyl ester;

6-[2-(7-Cyclopentanesulfonyl-4-oxo-4H-quinazolin-3-yl)-3-(tetrahydro-furan-2-yl)-propionylamino]-nicotinic acid methyl ester;

N-(5-Fluoro-pyridin-2-yl)-3-furan-2-yl-2-(7-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionamide;

N-(5-fluoropyridin-2-yl)-2-(7-(methylsulfonyl)-4-oxoquinazolin-3(4H)-yl)-3-(tetrahydrofuran-2-yl)propanamide;

2-(7-Cyclopentanesulfonyl-4-oxo-4H-quinazolin-3-yl)-N-(5-fluoro-pyridin-2-yl)-3-(tetrahydro-pyran-4-yl)-propionamide;

6-[3-Cyclohexyl-2-(7-cyclopropylmethanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinic acid methyl ester;

6-[3-Cyclohexyl-2-(7-cyclopropanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinamide;

6-[2-(8-Chloro-6-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-3-cyclohexyl-propionylamino]-nicotinamide;

6-[3-Cyclohexyl-2-(6-methanesulfonyl-4-oxo-4H-quinazolin-3-yl)-propionylamino]-nicotinamide;

N-(5-fluoropyridin-2-yl)-2-(7-(methylsulfonyl)-4-oxoquinazolin-3(4H)-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide;

3-(4,4-Difluorocyclohexyl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

N-cyclopropyl-3-(1-(5-fluoropyridin-2-ylamino)-1-oxo-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(3-Cyclohexyl-1-(5-fluoropyridin-2-ylamino)-1-oxopropan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(3-cyclohexyl-1-(5-fluoropyridin-2-ylamino)-1-oxopropan-2-yl)-N-cyclopropyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

N-cyclopropyl-3-(3-(3,5-difluorophenyl)-1-oxo-1-(thiazol-2-ylamino)propan-2-yl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

N-cyclopropyl-3-(3-(3,5-difluorophenyl)-1-oxo-1-(thiazol-2-ylamino) propan-2-yl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

3-(1-(5-Carbamoylpyridin-2-ylamino)-3-(3,5-difluorophenyl)-1-oxopropan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

N-cyclopropyl-3-(3-(4-fluorophenyl)-1-oxo-1-(thiazol-2-ylamino)propan-2-yl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

N-cyclopropyl-3-(3-(3-fluorophenyl)-1-oxo-1-(thiazol-2-ylamino)propan-2-yl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-cyclohexyl-2-(7-fluoro-6-(1-methyl-1H-imidazol-2-ylthio)-4-oxoquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)propan amide;

3-Cyclohexyl-2-(7-fluoro-6-(1-methyl-1H-imidazol-2-ylthio)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(5-methylthiazol-2-yl)propanamide;

3-cyclohexyl-2-(8-methoxy-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-(piperidin-1-yl)-N-(thiazol-2-yl)propanamide;

Benzyl 4-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-4-(thiazol-2-ylcarbamoyl)piperidine-1-carboxylate;

3-cyclohexyl-2-(8-methoxy-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-methoxy-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-methoxy-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-methoxy-2-methyl-4-oxoquinazolin-3(4-H)-yl)-N-(thiazol-2-yl)propanamide;

1-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)cyclopentanecarboxamide;

3-cyclohexyl-2-(8-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-methyl-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

2-(6-acetamido-4-oxoquinazolin-3(4H)-yl)-3-cyclohexyl-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(4-oxo-8-(trifluoromethyl)quinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

2-(8-chloro-4-oxoquinazolin-3(4H)-yl)-3-cyclohexyl-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6,8-dimethyl-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

2-(6-chloro-8-methyl-4-oxoquinazolin-3(4H)-yl)-3-cyclohexyl-N-(thiazol-2-yl)propanamide;

N-(5-chlorothiazol-2-yl)-3-cyclohexyl-2-(4-oxo-8-(trifluoromethyl)-quinazolin-3(4H)-yl)propanamide;

2-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)-thiazole-5-carboxylic acid;

6-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)-nicotinamide;

2-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)-N,N-diethylthiazole-5-carboxamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(morpholine-4-carbonyl)thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(4-methylpiperazine-1-carbonyl)thiazol-2-yl)propanamide;

N-(5-(4-acetylpiperazine-1-carbonyl)thiazol-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(4-(2-(isopropylamino)-2-oxoethyl)piperazine-1-carbonyl)thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-formylthiazol-2-yl)propanamide;

3-cyclohexyl-N-(5-((diethylamino)methyl)thiazol-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(morpholinomethyl)thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4)-yl)-N-(5-((4-methylpiperazin-1-yl)methyl)thiazol-2-yl)propanamide;

N-(5-((4-acetylpiperazin-1-yl)methyl)thiazol-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-((4-(2-(isopropylamino)-2-oxoethyl)piperazin-1-yl)methyl)thiazol-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(hydroxymethyl)thiazol-2-yl)propanamide;

2-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3 (4H)-yl)propanamido)isonicotinamide;

6-(3-cyclohexyl-2-(7-(methylsulfonyl)-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-fluoropyridin-2-yl)propanamide;

N-(5-chloropyridin-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

3-cyclohexyl-N-(4,6-dimethoxypyrimidin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

ethyl 4-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)-1-methyl-1H-imidazole-2-carboxy late;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-(morpholine-4-carbonyl)pyridin-2-yl)propanamide;

3-cyclohexyl-2-(7-(ethylsulfonyl)-4-oxoquinazolin-3(4H)-yl)-N-(5-(morpholine-4-carbonyl)pyridin-2-yl)propanamide;

N-(5-cyanopyridin-2-yl)-3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

N-(5-cyanopyridin-2-yl)-3-cyclohexyl-2-(7-(methylsulfonyl)-4-oxoquinazolin-3(4H)-yl)propanamide;

6-(3-cyclohexyl-2-(6-methoxy-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinamide;

N-(5-chloropyridin-2-yl)-3-cyclohexyl-2-(6-methoxy-4-oxoquinazolin-3(4H)-yl)propanamide;

3-(1-(5-carbamoylpyridin-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chloropyridin-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-cyclopropyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-cyclopentyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-cyclohexyl-2-(7-(cyclopropanesulfonamido)-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-methyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-(2-(dimethylamino)ethyl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-(2-(dimethylamino)ethyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-((1-methylpiperidin-4-yl)methyl)-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-3-cyclohexyl-1-oxopropan-2-yl)-N-((1-methylpiperidin-4-yl)methyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-1-oxo-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)-N-cyclopropyl-4-oxo-3,4-dihydroquinazoline-7-carboxamide;

3-(1-(5-chlorothiazol-2-ylamino)-1-oxo-3-(tetrahydro-2H-pyran-4-yl)propan-2-yl)-N-cyclopropyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(pyrimidin-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(pyrazin-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(pyrazin-2-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(1H-pyrazol-5-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(1H-pyrazol-5-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(5-methylpyridin-2-yl)propanamide;

methyl 6-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(isoxazol-3-yl)propanamide;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(quinolin-2-yl)propanamide;

methyl 6-(3-cyclohexyl-2-(4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)propanamido)nicotinate;

3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(oxazol-2-yl)propanamide;

3-cyclohexyl-2-(4-oxo-7-(trifluoromethyl)quinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

3-cyclohexyl-2-(7-fluoro-4-oxoquinazolin-3(4H)-yl)-N-(thiazol-2-yl)propanamide;

methyl 6-(3-cyclohexyl-2-(6,7-difluoro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

(S)-methyl 6-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

(R)-methyl 6-(3-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

methyl 6-(3-cyclohexyl-2-(7-fluoro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

methyl 6-(3-cyclohexyl-2-(6,8-dichloro-4-oxoquinazolin-3(4H)-yl)propanamido)nicotinate;

methyl 6-(2-(6-chloro-8-methyl-4-oxoquinazolin-3(4H)-yl)-3-cyclohexylpropanamido)nicotinate;

methyl 6-(3-cyclohexyl-2-(4-oxo-5-(trifluoromethyl)quinazolin-3(4H)-yl)propanamido)nicotinate;

methyl 6-(3-cyclohexyl-2-(4-oxo-8-(trifluoromethyl)quinazolin-3(4H)-yl)propanamido)nicotinate;

(S)-methyl 6-(3-cyclohexyl-2-(4-oxo-8-(trifluoromethyl)quinazolin-3(4H)-yl)propanamido)nicotinate;

(R)-methyl 6-(3-cyclohexyl-2-(4-oxo-8-(trifluoromethyl)quinazolin-3(4)-yl)propanamido)nicotinate;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-3-[4-(1,1-dioxo-(tetrahydro-2H-thiopyran-4-yl)]propanamide;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4)-yl)-3-[4-(1,1-dioxo-(tetrahydro-2H-thiopyran-4-yl)]propanamide;

N-(5-chloropyridin-2-yl)-4,4,4-trifluoro-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)butanamide;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-3-(1-(methylsulfonyl)piperidin-4-yl)propanamide;

N-(5-chloropyridin-2-yl)-3-cyclobutyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

N-(5-chloropyridin-2-yl)-3-(4,4-difluorocyclohexyl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-3-(3-fluoropyridin-2-yl)propanamide;

(S)—

N-(5-chloropyridin-2-yl)-4-cyclohexyl-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)butanamide;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-3-(4-(trifluoromethyl)cyclohexyl)propanamide;

N-(5-chloropyridin-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-3-(1-methyl-1H-pyrazol-4-yl)propanamide;

N-(5-chloropyridin-2-yl)-3-(3,5-dimethylisoxazol-4-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide;

N-(5-chlorothiazol-2-yl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)-3-(1-methyl-1H-pyrazol-4-yl)propanamide; and

N-(5-chloropyridin-2-yl)-3-(3,3-difluorocyclobutyl)-2-(6-fluoro-4-oxoquinazolin-3(4H)-yl)propanamide.

20. A process comprising:

reacting a compound comprising the formula

21. The process according to claim 20, comprising:

reacting the second reaction product with a compound comprising the formula

NHR₁R₂

under conditions that form a third reaction product comprising the formula

22. The process according to claim 20, comprising:

reacting the second reaction product with a compound comprising the formula

R₆-X

under conditions that form a fourth reaction product comprising the formula

23. A process comprising:

reacting a compound comprising the formula