Cyclic hydrocarbon compounds for the treatment of diseases

Patent metadata

Field	Value
Publication number	US-9487494-B2
Application number	US-74413708-A
Country	US
Kind code	B2
Filing date	Nov 20, 2008
Priority date	Nov 23, 2007
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The invention relates to novel cyclic hydrocarbon compounds and derivatives thereof, processes for the preparation thereof, to said compounds for use as a medicament, to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases with said compounds, and to the use of said compounds in the manufacture of medicaments.

First claim

The invention claimed is:

1. A compound of formula I

wherein

represents cycloalkyl comprising 4-7 carbon atoms optionally being substituted with one or more, same or different substituents selected from R 2 , R 3 , R 4 or R 5 ;
A represents 1-naphthyl;
R 1 is methyl, ethyl or n-propyl,

each of which are optionally substituted with one or more, same or different substituents selected from halogen or hydroxyl;
R 2 and R 3 represent hydrogen;
R 4 represents hydrogen, halogen, hydroxy, or C 1-6 alkyl;
each of R 5 represents independently one or more same or different substituents represented by hydrogen or C 1-6 alkyl;
G represents —C(O)H, —C(O)NH 2 , C 3-8 cycloalkyl, C 1-6 heterocycloalkyl, C 1-6 heterocycloalkenyl, C 3-8 cycloalkenyl, C 6-14 aryl, C 1-10 heteroaryl, C 6-10 arylamino, hydroxyaminocarbonyl, C 6-10 arylaminocarbonyl, C 1-4 aminocarbonyl, C 1-6 heterocycloalkylcarbonyl, C 1-10 heteroarylaminocarbonyl, C 6-10 arylsulfonylaminocarbonyl, C 6-14 aryloxy, C 1-4 alkoxycarbonyl,
wherein said —C(O)H, —C(O)NH 2 , C 3-8 cycloalkyl, C 1-6 heterocycloalkyl, C 1-6 heterocycloalkenyl, C 3-8 cycloalkenyl, C 6-14 aryl, C 1-10 heteroaryl, C 6-10 arylamino, hydroxyaminocarbonyl, C 6-10 arylaminocarbonyl, C 1-4 aminocarbonyl, C 1-6 heterocycloalkylcarbonyl, C 1-10 heteroarylaminocarbonyl, C 6-10 arylsulfonylaminocarbonyl, C 6-14 aryloxy, C 1-4 alkoxycarbonyl, are optionally further substituted with one or more, same or different substituents represented by halogen, cyano, carboxy, —NH 2 , C 1-6 amino, iminomethyl, hydroxyiminomethyl, amidino, hydroxy, mercapto, —C(O)H, —C(O)NH 2 , nitro, oxo, trifluoromethyl, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, aminoC 1-3 alkyl, C 1-6 haloalkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyl, C 1-4 aminocarbonyl, hydroxyaminocarbonyl, C 3-6 cycloalkylaminocarbonyl, C 1-6 heterocycloalkylaminocarbonyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 1-6 cycloalkylamino, C 1-6 heterocycloalkyl, C 1-6 heterocycloalkenyl, C 1-6 heterocycloalkylcarbonyl, C 6-14 aryl, carboxyC 6-10 aryl, C 1-6 heteroaryl, C 1-6 heteroarylaminocarbonyl, —S(O) 2 NH 2 , C 1-6 ureido, C 1-6 thioureido, C 1-4 alkylcarbonyloxy, C 1-4 alkoxycarbonyloxy, C 1-4 alkoxysulfonyloxy, C 1-6 heterocycloalkyloxy, C 1-4 alkylthio, C 1-4 aminosulfonyl, C 1-4 aminocarbonyloxy, C 1-4 alkylsulfonylamino, C 6-10 arylamino, C 6-10 arylaminocarbonyl, C 6-10 aryloxycarbonyl, C 1-4 alkoxycarbamoyl, C 6-10 arylcarbonylamino, C 6-10 arylsulfonylamino, C 1-4 alkylcarbonylamino, C 1-4 alkenylcarbonylamino, C 3-6 cycloalkenylcarbonylamino, C 3-6 cycloalkylcarbonylamino, C 1-4 alkoxycarbonylamino, C 1-6 heterocycloalkylcarbonylamino, C 1-4 alkylsulfonyl, C 1-6 heterocycloalkylsulfonyl or C 1-3 alkylsulfonylaminocarbonyl,
wherein said carboxy, C 1-6 amino, iminomethyl, hydroxyiminomethyl, C(O)NH 2 , C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, aminoC 1-3 alkyl, C 1-6 haloalkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyl, C 1-4 aminocarbonyl, hydroxyaminocarbonyl, C 3-6 cycloalkylaminocarbonyl, C 1-6 heterocycloalkylaminocarbonyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 1-6 cycloalkylamino, C 1-6 heterocycloalkyl, C 1-6 heterocycloalkenyl, C 1-6 heterocycloalkylcarbonyl, C 6-14 aryl, carboxyC 6-10 aryl, C 1-6 heteroaryl, C 1-6 heteroarylaminocarbonyl, —S(O) 2 NH 2 , C 1-6 ureido, C 1-6 thioureido, C 1-4 alkylcarbonyloxy, C 1-4 alkoxycarbonyloxy, C 1-4 alkoxysulfonyloxy, C 1-6 heterocycloalkyloxy, C 1-4 alkylthio, C 1-4 aminosulfonyl, C 1-4 aminocarbonyloxy, C 1-4 alkylsulfonylamino, C 6-10 arylamino, C 6-10 arylaminocarbonyl, C 6-10 aryloxycarbonyl, C 1-4 alkoxycarbamoyl, C 6-10 arylcarbonylamino, C 6-10 arylsulfonylamino, C 1-4 alkylcarbonylamino, C 1-4 alkenylcarbonylamino, C 3-6 cycloalkenylcarbonylamino, C 3-6 cycloalkylcarbonylamino, C 1-4 alkoxycarbonylamino, C 1-6 heterocycloalkylcarbonylamino, C 1-4 alkylsulfonyl, C 1-6 heterocycloalkylsulfonyl or C 1-3 alkylsulfonylaminocarbonyl, are optionally further substituted with one or more, same or different substituents selected from hydroxy, —NH 2 , C 1-6 amino, iminomethyl, hydroxyiminomethyl, carboxy, trifluoromethyl, halogen, oxo, mercapto, cyano, —C(O)NH 2 , nitro, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, C 1-6 haloalkyl, C 1-3 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, C 1-6 heterocycloalkyl, C 6-12 aryl, C 1-10 heteroaryl, C 1-3 alkoxyC 6-10 aryl, C 1-10 heterocycloalkylaryl, C 1-6 heterocycloalkenyl, —S(O) 2 NH 2 , —S(O) 2 OH, —S(O) 2 CH 3 , C 1-6 ureido, C 1-6 thioureido, C 1-4 alkylcarbonyloxy, C 1-4 alkoxycarbonyloxy, C 1-4 alkoxysulfonyloxy, C 1-4 alkoxycarbamoyl, C 1-4 aminocarbonyl, C 1-6 heterocycloalkylcarbonyl, C 1-4 alkylthio, C 1-4 aminosulfonyl, C 1-4 aminocarbonyloxy, C 1-4 alkylsulfonylamino, C 6-14 arylsulfonyl, C 6-10 arylsulfonylamino, hydroxyiminomethyl, C 1-4 alkylcarbonylamino or C 1-4 alkylsulfonyl,
wherein said —C(O)NH 2 , C 1-6 amino, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, C 1-6 haloalkyl, C 1-3 alkoxy, C 1-4 alkoxycarbonyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, C 1-6 heterocycloalkyl, C 6-12 aryl, C 1-10 heteroaryl, C 1-3 alkoxyC 6-10 aryl, C 1-10 heterocycloalkylaryl, C 1-6 heterocycloalkenyl, —S(O) 2 NH 2 , —S(O) 2 OH, C 1-6 ureido, C 1-6 thioureido, C 1-4 alkylcarbonyloxy, C 1-4 alkoxycarbonyloxy, C 1-4 alkoxysulfonyloxy, C 1-4 alkoxycarbamoyl, C 1-4 aminocarbonyl, C 1-6 heterocycloalkylcarbonyl, C 1-4 alkylthio, C 1-4 aminosulfonyl, C 1-4 aminocarbonyloxy, C 1-4 alkylsulfonylamino, C 6-14 arylsulfonyl, C 6-10 arylsulfonylamino, hydroxyiminomethyl, C 1-4 alkylcarbonylamino or C 1-4 alkylsulfonyl, are optionally further substituted with one or more, same or different substituents selected from hydroxy, oxo, cyano, halogen, C 1-3 alkoxy, C 1-3 alkoxyC 1-3 alkoxy, C 1-6 amino, mercapto, carboxy, —C(O)NH 2 , nitro, C 1-6 alkyl, C 1-3 hydroxyalkyl, C 1-4 alkoxycarbonyl, C 1-3 alkylcarbonylamino, C 1-6 heterocycloalkyl, C 6-12 aryl, C 1-6 heteroaryl, —S(O) 2 NH 2 or —S(O) 2 OH;
or G, together with R 4 , forms an oxo group;

or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof.

2. The compound according to claim 1 wherein compound I represents

3. The compound according to claim 1 or 2 , wherein

represents:

4. The compound according to claim 1 , wherein G represents —C(O)—R 6 ,
wherein R 6 represents —NH 2 , C 1-6 amino, hydroxy, mercapto, —C(O)NH 2 , trifluoromethyl, carboxy, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, C 1-6 haloalkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 aminocarbonyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 1-6 heterocycloalkenyl, C 3-6 cycloalkylamino, C 1-6 heterocycloalkyl, C 1-6 heterocycloalkylcarbonyl, C 6-14 aryl, C 1-6 heteroaryl, C 6-10 arylamino, carboxyC 6-10 aryl, C 1-4 alkylcarbonyloxy, C 1-4 alkoxycarbonyloxy, C 1-4 alkoxysulfonyloxy, C 1-4 alkylthio, C 1-4 aminocarbonyloxy, C 1-4 alkylsulfonylamino, C 1-4 alkylcarbonylamino, C 1-4 alkenylcarbonylamino, C 3-6 cycloalkenylcarbonylamino, C 3-6 cycloalkylcarbonylamino, C 1-4 alkoxycarbonylamino, C 6-10 arylcarbonylamino or C 6-10 arylsulfonylamino, wherein said C 1-6 amino, C 1-6 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 hydroxyalkyl, C 1-6 haloalkyl, C 1-4 a

Assignees

• Fensholdt Jef
• Havez Sophie Elisabeth
• Nørremark Bjarne
• Leo Pharma As

Inventors

• Fensholdt Jef
• Havez Sophie Elisabeth
• Nørremark Bjarne

Classifications

• A61P5/22

  for decreasing, blocking or antagonising the activity of calcitonin · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title