Organic compounds -- part of the class 532-570 series – Organic compounds – Cyclopentanohydrophenanthrene ring system containing
Reexamination Certificate
2001-06-26
2003-07-22
Dees, José G. (Department: 1616)
Organic compounds -- part of the class 532-570 series
Organic compounds
Cyclopentanohydrophenanthrene ring system containing
C514S169000, C514S177000, C514S178000, C514S179000, C514S182000, C540S002000, C540S106000, C540S120000, C552S502000, C552S515000, C552S518000, C552S519000, C552S526000, C552S531000, C552S610000, C552S611000, C552S623000, C552S625000, C552S650000
Reexamination Certificate
active
06596885
ABSTRACT:
The present invention relates to new 19-Nor steroids having a thiocarbonated chain in position 11beta, their preparation process and the intermediates of this process, their use as medicaments and the pharmaceutical compositions containing them.
A subject of the invention is the compounds of formula (I):
in which R
17
and R′
17
are such that:
either R
17
and R′
17
together form a ketone function, an oxime function, a hydrazono function or a methylene radical,
or R
17
is a hydroxyl radical, a hydroxymethyl radical or an acyloxy radical having at most 12 carbon atoms and R′
17
represents a hydrogen atom, an alkyl, alkenyl or alkynyl radical having at most 8 carbon atoms, each of these substituents being optionally substituted,
R
3
represents a hydrogen atom, a linear or branched alkyl radical or a cyclic alkyl radical having at most 8 carbon atoms or an acyl radical having at most 12 carbon atoms,
R
16
represents a hydrogen atom, a halogen atom or an alkyl radical having at most 8 carbon atoms, m has the value 0, 1 or 2, X, Y and Z are such that:
X represents a methylene radical, an arylene or arylenoxy group, having at most 10 carbon atoms linked to the steroid by a carbon atom,
Y represents a saturated or unsaturated, linear or branched aliphatic chain, containing 1 to 18 carbon atoms, optionally interrupted by an oxygen atom,
Z represents:
a linear or branched alkyl radical, containing 1 to 8 carbon atoms and optionally substituted, or an aryl or arylalkyl radical, each of these radicals being optionally substituted, in which the alkyl radical contains at most 6 carbon atoms and the aryl radical represents a monocyclic radical containing 5 or 6 members or a radical constituted by condensed rings containing 8 to 10 members, these radicals optionally containing one or more heteroatoms chosen from oxygen, nitrogen or sulphur atoms,
the alkyl radicals that can be represented by R′
17
and Z, the alkenyl or alkynyl radicals that can be represented by R′
17
and the aryl or arylalkyl radicals that can be represented by Z being optionally substituted by one or more radicals chosen from the following radicals:
halogens,
amino, alkylamino or dialkylamino in which the alkyl radical or radicals have 1 to 4 carbon atoms,
hydroxyl,
free, esterified or salified carboxy,
alkyl having 1 to 8 carbon atoms, optionally substituted by one or more halogen atoms,
oxo, cyano, nitro, formyl,
acyl or acyloxy having at most 12 carbon atoms,
alkoxy or alkylthio having 1 to 4 carbon atoms,
carbamoyl,
alkenyl or alkynyl having at most 4 carbon atoms,
aryl as defined above, and the addition salts of the above.
By acyloxy radical can be meant in particular the derivative of a saturated or unsaturated aliphatic or cycloaliphatic acid and notably an alkanoic acid such as, for example, acetic, propionic, butyric or isobutyric, valeric or undecylic acid, a hydroxyalkanoic acid such as, for example, hydroxyacetic acid; a cycloalkylcarboxylic or cycloalkylalkanoic acid such as, for example, cyclopropyl, cyclopentyl or cyclohexylcarboxylic, cyclopentyl or cyclohexyl acetic or propionic acid, a benzoic acid, a salicylic acid or a phenylalkanoic acid such as phenyl acetic or phenyl propionic acid, an amino acid such as diethylamino acetic or aspartic acid, formic acid or an optionally salified diacid, such as, for example, butanedioic acid or the monosodium salt of the latter. It is preferably the derivative of acetic, propionic or butyric acid.
By acyl radical is meant the radicals corresponding to the previous acyloxy radicals.
By alkyl radical can be meant one of the following radicals: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, n-pentyl, n-hexyl, 2-methyl pentyl, 2,3-dimethyl butyl, n-heptyl, 2-methyl hexyl, 2,2-dimethyl pentyl, 3,3-dimethyl pentyl, 3-ethylpentyl, n-octyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 3-methyl 3-ethyl pentyl.
It is preferably the methyl radical.
When R
3
represents a cyclic alkyl radical, it can be a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical. It is preferably the cyclopentyl radical.
By alkoxy radical, can notably be meant the methoxy, ethoxy, propyloxy, butyloxy radical and by alkylthio radical, can notably be meant the methylthio, ethylthio, propylthio or butylthio radicals.
By alkenyl radical, can be meant a vinyl, propenyl, isopropenyl, allyl, 2-methyl allyl, butenyl or isobutenyl radical. It is preferably the vinyl or propenyl radical.
By alkynyl radical, can be meant the ethynyl, propynyl, propargyl, butynyl or isobutynyl radical. It is preferably the ethynyl or propynyl radical.
When R
16
represents a halogen atom, it can be a bromine, chlorine, fluorine or iodine atom; it is preferably a bromine atom.
When X represents an arylene group, it is preferably the phenylene radical.
When X represents an arylenoxy group, it is preferably the phenylenoxy radical.
When Y represents a saturated or unsaturated, linear or branched aliphatic chain, it can be one of the following radicals: methylene, ethylene, propylene, isopropylene, butylene, isobutylene, or tert-butylene, n-pentylene, n-hexylene, 2-methyl pentylene, 2,3-dimethyl butylene, n-heptylene, 2-methyl hexylene, 2,2-dimethyl pentylene, 3,3-dimethyl pentylene, 3-ethyl-pentylene, n-octylene, 2,2-dimethyl hexylene, 3,3-dimethyl hexylene, 3-methyl 3-ethyl pentylene, nonylene, 2,4-dimethyl heptylene, n-decylene, n-undecylene, n-dodecylene, n-tridecylene, n-tetradecylene, n-pentadecylene, n-hexadecylene, n-heptadecylene or n-octadecylene, preferably n-pentylene, n-hexylene, n-heptylene, n-octylene or n-nonylene.
It can also be vinylene, isopropenylene, allylene, 2-methyl allylene, isobutenylene, butenylene, pentenylene, hexenylene, heptenylene or octenylene radicals, preferably the hexenylene radical.
It can also be ethynylene, propynylene, propargenylene, butynylene, isobutynylene, pentynylene, hexynylene, heptynylene or octenylene radicals, preferably the propynylene, hexynylene or octynylene radicals.
It can be a chain interrupted by an oxygen atom, for example, an oxapolymethylene radical, preferably the oxy diethylene radical.
When Z represents a linear or branched alkyl radical, it can be the radicals indicated above, preferably propyl, butyl, n-pentyl.
When Z represents an arylalkyl group, the alkyl radical can be one of the radicals defined above, notably a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, n-pentyl or n-hexyl radical, it is preferably the methyl or ethyl radical.
By aryl group which can be contained in an arylalkyl group, is meant:
a carbocyclic monocyclic radical, for example the phenyl radical,
a heterocyclic monocyclic radical, for example the following radicals: thienyl, furyl, pyrannyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazolyl, oxazolyl, furazannyl, pyrrolinyl, imidazolinyl, pyrazolinyl, thiazolinyl, triazolyl, tetrazolyl, as well as the isomers of position of the heteroatom or heteroatoms that these radicals can contain,
a radical constituted by carbocyclic condensed rings, for example, the naphthyl radical or phenanthrenyl radical,
a radical constituted by heterocyclic condensed rings, for example, benzofurannyl, benzothienyl, benzimidazolyl, benzothiazolyl, naphtho[2,3-b]thienyl, thianthrenyl, isobenzofurannyl, chromenyl, xanthenyl, phenoxathiinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, indolinyl, isoindolinyl, imidazopyridyl, imidazopyrimidinyl or also the condensed polycyclic systems constituted by heterocyclic monocyclics, as defined, for example, above, such as for example furo[2,3-b]pyrrole or thieno[2,3-b]furan.
When Z represents an aryl or arylalkyl group, there can be mentioned as examples of such an aryl radical, in particular, the following radicals: phenyl, furyl such as 2-furyl, imidazolyl such as 2-imidazolyl, pyridyl such as
Claussner Andre
Nique Francois
Teutsch Jean-Georges
Van de Velde Patrick
Aventis Pharma S.A.
Choi Frank
Dees Jos,e G.
Muserlian Lucas and Mercanti
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