Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
1998-12-11
2003-11-04
Qazi, Sabiha (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S167000, C514S172000, C514S374000, C514S378000, C514S375000, C514S379000, C548S237000, C548S239000, C552S653000
Reexamination Certificate
active
06642218
ABSTRACT:
This invention relates to vitamin D derivatives with substituents at C-25 of general formula I
in which
Y
1
means a hydrogen atom, a hydroxyl group, an alkanoyloxy group with 1 to 12 C atoms or an aroyloxy group,
Y
2
means a hydrogen atom or an alkanoyl group with 1 to 12 C atoms or an aroyl group,
R
1
and R
2
each mean a hydrogen atom or together an exocyclic methylene group,
R
3
and R
4
, independently of one another, mean a hydrogen atom, a chlorine or fluorine atom, an alkyl group with 1 to 4 carbon atoms, together a methylene group or together with quaternary carbon atom 20 a 3- to 7-membered, saturated or unsaturated carbocyclic ring,
Q means a straight-chain or branched carbon unit with up to 10 carbon atoms, which at any positions can have hydroxyl groups (in &agr;- or &bgr;-position), which in turn can be etherified or esterified, keto groups, amino groups or halogen atoms,
R
5
and R
6
at the same time each mean a hydrogen atom, a chlorine or fluorine atom, a trifluoromethyl group, a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 4 carbon atoms or R
5
and R
6
together with carbon atom 25 mean a 3- to 7-membered, saturated or unsaturated carbocyclic ring and
Z means a five- or six-membered carbo- or heterocyclic ring, which can be saturated, unsaturated or aromatic, and at any positions one or more alkyl chains, which can be straight-chain or branched, saturated or unsaturated, and at any points can be interrupted by oxa, thia or aza groups (substituted or unsubstituted) or sulfoxide or sulfo groups or can carry substituents (hydroxy groups, halogen atoms),
process for their production, intermediate products in the production process as well as their use for the production of pharmaceutical agents.
The alkanoyl or alkanoyloxy groups with 1 to 12 C atoms that are possible for radicals Y
1
and Y
2
are derived especially from saturated carboxylic acids. These radicals can be cyclic, acyclic, carbocyclic or heterocyclic. The preferred radicals are derived from C
1
to C
9
, especially C
2
to C
5
alkanecarboxylic acids, such as, for example, acetyl(oxy), propionyl(oxy), and butyryl(oxy).
As aroyl(oxy) groups, the benzoyl(oxy) groups and substituted benzoyl(oxy) groups are preferred.
For R
3
and R
4
, the following preferred combinations apply: R
3
=H, R
4
=methyl or R
3
=methyl, R
4
=H; R
3
=F, R
4
=methyl or R
3
=methyl, R
4
=F; R
3
, R
4
=methyl; R
3
and R
4
together form a methylene group or together with tertiary carbon atom 20 form a cyclopropyl ring.
For Q, the following preferences apply:
Q is an unsubstituted, unbranched alkyl unit with 1, 2 or 3 carbon atoms or
Q is a hydroxymethylene group (hydroxyl group in &agr;- or &bgr;-position) or
Q=—CH(OH)—CH
2
— or —CH(OH)—CH
2
—CH
2
— (hydroxyl groups in &agr;- or &bgr;-position),
substituents, preferably alkyl groups, for all described variants at C-24a are possible.
For R
5
and R
6
, the following preferences apply:
R
5
=R
6
=methyl or ethyl; R
5
and R
6
together with carbon atom C-25 form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring.
Especially preferred are the cases: R
5
=R
6
=methyl, and R
5
and R
6
together with carbon atom C-25 form a cyclopropyl ring.
For Z, the following preferences apply:
For the five-membered case, furan, tetrahydrofuran, thiophene, pyrrole, pyrrolidine, imidazole, pyrazole, oxazole, thiazole, isoxazole, triazole, oxadiazole or thiadiazole rings, which at any positions can carry one or more alkyl chains with 1 to 12 carbon atoms, are preferred. These alkyl chains can be straight-chain or branched, saturated or unsaturated and can be interrupted by heteroatoms (O, S, N also substituted). They can also carry other substituents (hydroxyl groups, halogen atoms).
For the six-membered case, the phenyl, pyridine, pyrazine, pyrimidine, pyridazine, piperidine or tetrahydropyran rings are preferred, which, like the five-membered rings, can be substituted in one or more places with the above-mentioned alkyl chains.
Especially preferred are: imidazole, oxazole, thiazole, furan, thiophene, pyrrole, isoxazole, pyrazole, triazole, pyridine, pyrimidine and phenyl rings, which each carry a straight-chain, saturated C1 to C12 alkyl chain.
Especially preferred according to this invention are the following compounds:
(5Z,7E,22E)-(1S,3R,24R)-25-(5-Propyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-propyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-methyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-methyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-ethyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-ethyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-butyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-butyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-pentyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-pentyloxazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-propylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-propylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-methylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-methylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-ethylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-ethylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-butylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-butylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-pentylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-pentylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-propylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-propylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-methylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-methylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-ethylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-ethylthiazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-butylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-butylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-pentylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-pentylimidazol-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24R)-25-(5-propylfuran-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5Z,7E,22E)-(1S,3R,24S)-25-(5-propylfuran-2-yl)-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-1,3,24-triol
(5
Fahnrich Marianne
Haberey Martin
Kirsch Gerald
Neef Günter
Schwarz Katica
Millen White Zelano & Branigan P.C.
Qazi Sabiha
Schering Aktiengesellschaft
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