US 2004/0073037 A1Published application

Acyl sulfamides for treatment of obesity, diabetes and lipid disorders

AssigneeMerck & Co., Inc.

InventorsA. Brian Jones, John J. Acton III

Life of this patent

Estimating the term…

Abstract

A class of acyl sulfamides comprises compounds that are potent ligands for PPAR gamma and generally have antagonist or partial agonist activity. The compounds may be useful in the treatment, control or prevention of obesity, non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, inflammation, and other PPAR gamma mediated diseases, disorders and conditions.

Claims30

Dependent claims

A compound having the formula I:

65
including pharmaceutically acceptable salts and prodrugs thereof, wherein
X is selected from CH and N;
R1 is —(CH2)a(Y1)b(Z)c(Y2)dR4;
a, b, c, and d are each independently 0 or 1, with the proviso that if c is 0, then b and d are not both 1;
Y1 and Y2 are each independently O or NH;
Z is selected from C(O) and S(O)2;
R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 Cycloalkyl, C6-10 Aryl, Heteroaryl, and Heterocycle, and R2 is optionally substituted with 1-5 groups R3;
Each R3 is independently selected from H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 Aryl, —OC1-6 alkyl, —OC2-6 alkenyl, —OC2-6 alkynyl, —OC6-10 Aryl, C3-6 Cycloalkyl, Heteroaryl, Heterocycle, CN, NO2, S(O)mR4, SO2NHR4, SO2NR4R4, CO2H, and CONHR4, wherein each alkyl, alkenyl, alkynyl, Aryl, -Oalkyl, -Oalkenyl, -Oalkynyl, -Oaryl, Cycloalkyl, Heteroaryl, and Heterocycle is optionally substituted with 1-5 substituents independently selected from halogen, —OCF3, —OCH3, CF3 and CH3;
Each R4 is independently selected from the group consisting of H, C1-10 alkyl, C3-10 Cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C6-10 Aryl, Heterocycle, and Heteroaryl, wherein R4 is optionally substituted with 1-3 groups R5;
Each R5 is independently selected from halogen, C1-6 alkyl, C6-10 Aryl, —OC16 alkyl, —OC2-6 alkenyl, —OC2-6 alkynyl, —OC6-10 Aryl, C3-6 Cycloalkyl, CN, NO2, CO2H, CO2C1-C6alkyl and CONH2, wherein each alkyl, Aryl, -Oalkyl, -Oalkenyl, -Oalkynyl, -Oaryl, Cycloalkyl and CO2alkyl is optionally substituted with 1-5 substituents independently selected from halogen, —OCF3, —OCH3, CF3 and CH3;
m is 0, 1 or 2;
Each alkyl, alkenyl and alkynyl group may be linear or branched;
Cycloalkyl is a saturated or partly saturated monocyclic or bicyclic carbocyclic ring system;
Aryl is a monocyclic or bicyclic carbocyclic aromatic ring system;
Heterocycle is a fully saturated or partially saturated monocyclic or bicyclic ring system comprising at least one heteroatom selected from N, S and O in the ring and comprising 4 to 11 atoms in the ring;
and
Heteroaryl is a monocyclic or bicyclic aromatic ring system comprising at least one ring heteroatom selected from N, O and S and comprising 4-11 atoms in the ring or rings.

15 more elements

A compound represented by any of the compounds of Examples 1-20, and pharmaceutically acceptable salts and prodrugs thereof, named below:

1. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl benzoate;
2. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl pentanoate;
3. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl phenylcarbamate;
4. (4-{[({[3,5-bis(trifluoromethyl)benzoyl]amino}-sulfonyl)amino]methyl}cyclohexyl)methyl phenylcarcarbamate;
5. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl benzylcarbamate;
6. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl 2-phenylethylcarbamate;
7. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl 3-methoxyphenylcarbamate;
8. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl butylcarbamate;
9. (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl 1-methylbutylcarbamate;
10. N-benzyl-N′-[3,5-bis(trifluoromethyl)benzoyl]-N-({4-[(pentyloxy)methyl]cyclohexyl}methyl)sulfamide;
11. N-benzyl-4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexane carboxamide;
12. N-[(4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl]phenylurea;
13. N-[(4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl ]pentanamide;
14. N-[(4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl]benzamide;
15. N-[(4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl]-N′-butylurea;
16. Butyl (4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl carbamate;
17. N-[(4-{[benzyl({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)amino]methyl}-cyclohexyl)methyl]benzenesulfonamide;
18. (4-{[({[3,5-bis(trifluoromethyl)benzoyl]amino}sulfonyl)(ethyl)amino]methyl}-cyclohexyl)methyl phenylcarbamate;
19. {4-[(benzyl{[(3,5-dimethylbenzoyl)amino]sulfonyl}amino)methyl]cyclohexyl}methyl-phenylcarbamate;
and
20. 4-(benzyl-{[(4-t-butylbenzoyl)amino]sulfonyl}aminomethyl)-1-piperidinecarboxylic acid phenylmethyl ester.

18 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/470,483Filed 29 Jul 2003
Published: 15 Apr 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification35 codes

C07C 307/06
Diamides of sulfuric acids: having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
F16M 11/22
Undercarriages with or without wheels: with approximately constant height, e.g. with constant length of column or of legs
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes

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US 6,852,738 B2Related patent
US 2004/0073037 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound having the formula I:

65
including pharmaceutically acceptable salts and prodrugs thereof, wherein
X is selected from CH and N;
R1 is —(CH2)a(Y1)b(Z)c(Y2)dR4;
a, b, c, and d are each independently 0 or 1, with the proviso that if c is 0, then b and d are not both 1;
Y1 and Y2 are each independently O or NH;
Z is selected from C(O) and S(O)2;
R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 Cycloalkyl, C6-10 Aryl, Heteroaryl, and Heterocycle, and R2 is optionally substituted with 1-5 groups R3;
Each R3 is independently selected from H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 Aryl, —OC1-6 alkyl, —OC2-6 alkenyl, —OC2-6 alkynyl, —OC6-10 Aryl, C3-6 Cycloalkyl, Heteroaryl, Heterocycle, CN, NO2, S(O)mR4, SO2NHR4, SO2NR4R4, CO2H, and CONHR4, wherein each alkyl, alkenyl, alkynyl, Aryl, -Oalkyl, -Oalkenyl, -Oalkynyl, -Oaryl, Cycloalkyl, Heteroaryl, and Heterocycle is optionally substituted with 1-5 substituents independently selected from halogen, —OCF3, —OCH3, CF3 and CH3;
Each R4 is independently selected from the group consisting of H, C1-10 alkyl, C3-10 Cycloalkyl, C2-10 alkenyl, C2-10 alkynyl, C6-10 Aryl, Heterocycle, and Heteroaryl, wherein R4 is optionally substituted with 1-3 groups R5;
Each R5 is independently selected from halogen, C1-6 alkyl, C6-10 Aryl, —OC16 alkyl, —OC2-6 alkenyl, —OC2-6 alkynyl, —OC6-10 Aryl, C3-6 Cycloalkyl, CN, NO2, CO2H, CO2C1-C6alkyl and CONH2, wherein each alkyl, Aryl, -Oalkyl, -Oalkenyl, -Oalkynyl, -Oaryl, Cycloalkyl and CO2alkyl is optionally substituted with 1-5 substituents independently selected from halogen, —OCF3, —OCH3, CF3 and CH3;
m is 0, 1 or 2;
Each alkyl, alkenyl and alkynyl group may be linear or branched;
Cycloalkyl is a saturated or partly saturated monocyclic or bicyclic carbocyclic ring system;
Aryl is a monocyclic or bicyclic carbocyclic aromatic ring system;
Heterocycle is a fully saturated or partially saturated monocyclic or bicyclic ring system comprising at least one heteroatom selected from N, S and O in the ring and comprising 4 to 11 atoms in the ring;
and
Heteroaryl is a monocyclic or bicyclic aromatic ring system comprising at least one ring heteroatom selected from N, O and S and comprising 4-11 atoms in the ring or rings.

15 more elements

Facts

Application

10/470,483Filed 29 Jul 2003

Published

15 Apr 2004

Term ends

Not estimatedThe source records don’t support an estimate.

Classification35 codes

C07C 307/06
Diamides of sulfuric acids: having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
F16M 11/22
Undercarriages with or without wheels: with approximately constant height, e.g. with constant length of column or of legs
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes