Chemical compounds and use thereof for improving muscular quality
Chemical compounds and the therapeutic use thereof, in particular for improving muscular quality in mammals. More particularly, a method of improving muscular quality in sarcopenic mammals and treating and/or preventing sarcopenia using the chemical compounds and, in particular, sarcopenic obesity and the associated complications and/or pathologies thereof, such as loss of strength, muscle mass, performance and of physical and movement capacity. Also, a method of improving muscle quality in obese mammals and treating and/or preventing of obesity and associated complications and/or pathologies, advantageously type 2 diabetes and metabolic syndrome, using the chemical compounds.
1. A compound of formula (I) below:
wherein:
V—U is a carbon-carbon single bond and Y is a hydroxyl group or a hydrogen, or V—U is a C═C ethylenic bond;
X is chosen from: an oxygen; an N—OR 5 group,
R 5 then being chosen from: a hydrogen; a C 1 -C 6 alkyl group optionally having unsaturations on the chain; a (C 1 -C 6 )CO 2 R 6 group with R 6 possibly being a hydrogen or a C 1 -C 6 group; a (C 1 -C 6 )OR 7 group, R 7 being an aromatic or heteroaromatic ring optionally monosubstituted or polysubstituted with an alkyl or alkoxyl group, CF 3 , Cl; a (C 1 -C 6 )NR 8 R 9 group, R 8 and R 9 being C 1 -C 6 groups, or (C 1 -C 6 )N(C 1 -C 6 ) groups or (C 1 -C 6 )N(C 1 -C 6 )OR 6 groups with R 6 as defined above, NR 8 R 9 can also be a heterocycle; and
wherein:
Q is a carbonyl group;
with R 1 being chosen from: a (C 1 -C 6 )W(C 1 -C 6 ) group; a (C 1 -C 6 )W(C 1 -C 6 )W(C 1 -C 6 ) group; a (C 1 -C 6 )W(C 1 -C 6 )CO 2 (C 1 -C 6 ) group; a (C 1 -C 6 )A group, A representing a heterocycle optionally substituted with a group of the type OH, OMe, (C 1 -C 6 ), N(C 1 -C 6 ) or CO 2 (C 1 -C 6 ); a CH 2 Br group;
W being a heteroatom chosen from N, O and S; and
the compound being in the form of an enantiomer, a diastereoisomer, a hydrate, a tautomer, a racemic mixture or a pharmaceutically acceptable salt.
2. The compound as claimed in claim 1 , wherein, in formula (I), Q represents a carbonyl group.
3. The compound as claimed in claim 2 , wherein, in formula (I):
X is an oxygen;
V—U is a carbon-carbon single bond;
Y is a hydroxyl group;
R 1 is chosen from: a (C 1 -C 6 )W(C 1 -C 6 ) group; a (C 1 -C 6 )W(C 1 -C 6 )W(C 1 -C 6 ) group; a (C 1 -C 6 )W(C 1 -C 6 )CO 2 (C 1 -C 6 ) group; a (C 1 -C 6 )A group, A representing a heterocycle optionally substituted with a group of the type OH, OMe, (C 1 -C 6 ), N(C 1 -C 6 ) or CO 2 (C 1 -C 6 ); and
W being a heteroatom chosen from N, O and S.
4. The compound as claimed in claim 1 , wherein, in formula (I), V—U is a C═C ethylenic bond.
5. The compound as claimed in claim 1 , wherein, in formula (I), X is an N—OR 5 group.
6. The compound as claimed in claim 1 , chosen from the following compounds:
No. 81: (2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-10,13-dimethyl-17-(2-morpholinoacetyl)-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one;
No. 86: (2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-17-[2-(3-hydroxypyrrolidin-1-yl)acetyl]-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one;
No. 88: (2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-17-[2-(4-hydroxy-1-piperidyl)acetyl]-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one;
No. 89: (2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-17-[2-[4-(2-hydroxyethyl)-1-piperidyl]acetyl]-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one;
No. 91: (2S,3R,5R,10R,13R,14S,17S)-17-[2-(3-dimethylaminopropyl(methyl)amino)acetyl]-2,3,14-trihydroxy-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one;
No. 92: 2-[2-oxo-2-[(2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-10,13-dimethyl-6-oxo-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]ethyl]sulfanylacetate ethyl;
No. 93: (2S,3R,5R,10R,13R,14S,17S)-17-(2-ethylsulfanylacetyl)-2,3,14-trihydroxy-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one; and
No. 94: (2S,3R,5R,10R,13R,14S,17S)-2,3,14-trihydroxy-17-[2-(2-hydroxyethylsulfanyl)acetyl]-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one.
7. A pharmaceutical composition comprising the compound as claimed in claim 1 and a pharmaceutically acceptable carrier.
8. A method of treating sarcopenia and associated complications or pathological conditions thereof using the chemical compound as claimed in claim 1 .
9. The method as claimed in claim 8 for treating loss of strength, loss of muscle mass, loss of physical performance and capacity, and loss of mobility in mammals.
10. A method of treating obesity and associated complications or pathological conditions thereof using the chemical compound as claimed in claim 1 .
11. A method of treating a sarcopenic obesity and associated complications or pathological conditions thereof using the chemical compound as claimed in claim 1 .
12. The method as claimed in claim 11 for treating loss of strength, loss of muscle mass, loss of physical performance and capacity, and loss of mobility in mammals.
13. The method as claimed in claim 10 for treating type 2 diabetes or metabolic syndrome in mammals.