Organic compounds
The present invention relates to compounds selected from the group consisting of 14-0-[((Mono- or dialkylamino)-cycloalkylsulfanyl- or -cycloalkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, 14-O-[((Cycloalkyl- or heterocyclylamino)-cycloalkylsulfanyl- or -cycloalkyl-oxy)-acetyl, -thioaceyl or -imino-oxy]-mutilins, 14-O-[((Heterocyc-N-yl-cycloalkyl)-sulfanyl- or -oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, 14-O-[(((Mono- or dialkylamino)-cycloalkyl)-alkylsulfanyl- or -alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, 14-O-[(((Cycloalkyl- or heterocyclylamino)-cycloalkyl)-alkylsulfanyl- or -alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, and 14-O-[((Heterocyc-N-yl-cycloalkyl)-alkylsulfanyl- or -alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, and their use as pharmaceuticals.
1. A compound having formula Ip:
wherein,
R is hydrogen or (C 1-8 )alkyl,
R 1 is
(C 3-12 )cycloalkyl,
unsubstituted (C 1-8 )alkyl, or
(C 1-8 )alkyl substituted by
hydroxy,
halogen,
(C 1-6 )alkyloxycarbonyl;
(C 1-4 )alkylaminocarbonyl;
(C 3-8 )cycloalkyl or cyclohexyl,
(C 6-18 )aryl, or
a heterocyclic group comprising 3 to 7 ring members, 1 to 4 heteroatoms selected from the group consisting of N, O and S, optionally anellated with another ring system,
R 2 is hydrogen or (C 1-4 )alkyl,
q is a number selected from 0, 1 and 2; and
the group (NRR 1 ) is in position 3 or in position 4 of the cycloalkyl ring.
2. The compound according to claim 1 having formula Ipp:
wherein R, R 1 and q are as defined in claim 1 .
3. A compound as claimed in claim 1 in the form of a salt.
4. A pharmaceutical composition comprising a compound according to claim 1 , optionally in the form of a salt, in association with at least one pharmaceutical excipient, optionally further comprising another pharmaceutically active agent.
5. The compound as claimed in claim 2 in the form of a salt.
6. A pharmaceutical composition comprising a compound according to claim 2 , optionally in the form of a salt, in association with at least one pharmaceutical excipient, optionally further comprising another pharmaceutically active agent.
7. A compound according to claim 1 , which is selected from the group consisting of:
14-O—[(3-Diethylamino-cyclohexan-1-yl)-sulfanylacetyl]-mutilin,
14-O-{[(3-Methylamino-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Ethylamino-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Ethylamino-1-methyl-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Ethylamino-2-methyl-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[3-Ethylamino-cyclohexanylsulfanyl]-acetyl}-mutilin,
14-O-{[3-(sec-Butylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-[((3-(sec-Butylamino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[((1-(sec-Butylamino)-cycloheptan-3-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[3-(2,2,2-Trifluoro-ethylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[3-(2,2,2-Trifluoro-ethylamino)-cyclohexan-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[3-(2,2-Difluoro-ethylamino)-cyclohexan-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[(3-(2-Hydroxy-ethylamino)-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[3-(2-Hydroxy-propylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-[((3-(1-Isopropyl-2-hydroxy-ethylamino)-cyclopent-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-[((3-(1-Isopropyl-2-hydroxy-ethylamino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[3-(2-Hydroxy-1-hydroxymethyl-1-methyl-ethylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[3-(2-Hydroxy-1,1-bis-hydroxymethyl-ethylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-[((3-(Methoxycarbonyl-methylamino)-cyclopent-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[((3-(Ethoxycarbonyl-methylamino)-cyclopent-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[(((3-(Isopropoxycarbonyl-methylamino)-cyclopent-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[3-(Methoxypropionyl-2-amino)-cyclopent-1-yl-sulfanyl]-acetyl}-mutilin,
14-O-{[3-(Isopropoxypropionyl-2-amino)-cyclopent-1-yl-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Methylcarbamoylmethylamino-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O—[(((3-(1-Cyclohexylethyl)-amino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[(((3-(Phenylethyl)-amino)-cyclopentan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[(((3-(Phenylethyl)-amino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[3-(1H-Benzoimidazol-2-ylmethylamino)-cyclopent-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[(3-Dimethylamino-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Diethylamino-cyclopent-1)-yl)-sulfanyl]-acetyl}-mutilin,
14-O-[((3-Diethylamino-cycloheptan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[(3-Cyclopropylamino-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-{[(3-Cyclopropylamino-cyclohexan-1-yl)-sulfanyl]-acetyl}-mutilin,
14-O-[((3-(Morpholin-4-yl)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[(3-(1H-Imidazol-2-ylamino)-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin, and
14-O-{[(3-(1H-Benzoimidazol-2-ylamino)-cyclopent-1-yl)-sulfanyl]-acetyl}-mutilin.
8. A compound as claimed in claim 7 in the form of a salt.
9. A pharmaceutical composition comprising a compound according to claim 7 , optionally in the form of a salt, in association with at least one pharmaceutical excipient, optionally further comprising another pharmaceutically active agent.
10. A compound having formula Ip:
wherein
R is hydrogen or (C 1-8 )alkyl,
R 1 is unsubstituted (C 1-8 )alkyl,
R 2 is hydrogen or (C 1-4 )alkyl,
q is 1; and
the group (NRR 1 ) is in position 3 or in position 4 of the cycloalkyl ring.
11. The compound according to claim 10 having formula Ipp:
wherein R, R 1 and q are as defined in claim 1 .
12. A compound according claim 10 , which is selected from the group consisting of
14-O-[(3-Diethylamino-cyclohexan-1-yl)-sulfanylacetyl]-mutilin,
14-O-{[3-Ethylamino-cyclohexanylsulfanyl]-acetyl}-mutilin,
14-O-[((3-(sec-Butylamino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[3-(2,2,2-Trifluoro-ethylamino)-cyclohexan-1-ylsulfanyl]-acetyl}-mutilin,
14-O-{[3-(2,2-Difluoro-ethylamino)-cyclohexan-1-ylsulfanyl]-acetyl}-mutilin,
14-O-[((3-(1-Isopropyl-2-hydroxy-ethylamino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[(((3-(1-Cyclohexylethyl)-amino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O—[(((3-(Phenylethyl)-amino)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin,
14-O-{[(3-Cyclopropylamino-cyclohexan-1-yl)-sulfanyl]-acetyl}-mutilin, and
14-O-[((3-(Morpholin-4-yl)-cyclohexan-1-yl)-sulfanyl)-acetyl]-mutilin.
13. A compound of claim 10 in the form of a salt.
14. A pharmaceutical composition comprising a compound of claim 10 , optionally in the form of a salt, in association with at least one pharmaceutical excipient.
15. The compound according to claim 11 in the form of a salt.
16. A pharmaceutical composition comprising a compound of claim 11 , optionally in the form of a salt, in association with at least one pharmaceutical excipient.
17. A compound according to claim 12 in the form of a salt.
18. A pharmaceutical composition comprising a compound of claim 12 , optionally in the form of a salt, in association with at least one pharmaceutical excipient.