US2007105858A1PendingUtilityA1
Retinoic acid mimetic anilides
Est. expiryDec 11, 2017(expired)· nominal 20-yr term from priority
Inventors:Dominique Jean-Pierre MabireChristophe Denis AdelinetImre Christian Francis CsokaMarc Gaston Venet
A61P 43/00C07D 233/61C07D 417/12C07D 413/12C07D 231/12C07D 233/56C07D 249/08A61P 17/00C07D 401/12C07D 405/12C07D 403/12C07D 409/12
59
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Claims
Abstract
The present invention is concerned with compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein X represents O, S or NR 3 ; R 1 represents hydrogen, hydroxy, C 1-6 alkyl or aryl; R 2 represents hydrogen; optionally substituted C 1-12 alkyl; C 3-7 cycloalkyl; C 2-8 alkenyl; aryl; Het 1 ; or R 1 and R 2 taken together may form a bivalent radical of formula —(CH 2 ) n — wherein n is 2, 3, 4, 5 or 6; R 3 represents hydrogen, optionally substituted C 1-6 alkyl, aryl, Het 1 ; R 4 represents hydrogen; hydroxy; mercapto; C 1-6 alkyloxy; C 1-6 alkylthio; aryloxy; arylthio; Het 1 -oxy; Het 1 -thio; optionally substituted C 1-12 alkyl; optionally substituted C 2-8 alkenyl; optionally substituted C 2-8 alkynyl; optionally substituted C 3-7 cycloalkyl; optionally substituted C 5-7 cycloalkenyl; aryl; Het 1 ; or -Alk-NR 3 R 5 (i) or —NR 3 R 5 (ii) wherein Alk represents C 1-6 alkanediyl; and R 5 represents hydrogen, C 1-6 alkyl, aryl, Het 1 , (aryl or Het 1 )C 1-6 alkyl, (aryl or Het 1 )carbonyl or (aryl or Het 1 )C 1-6 alkyloxycarbonyl; aryl represents optionally substituted indanyl, indenyl, naphtyl, 5,6,7,8-tetrahydro-2-naphtalenyl or phenyl; Het represents an optionally substituted unsaturated heterocycle; and Het 1 represents an optionally substituted monocyclic or bicyclic heterocycle; having retinoic mimetic activity; their preparation, compositions containing them and their use as a medicine.
Claims
exact text as granted — not AI-modified1 - 14 . (canceled)
15 . A compound having the formula
a N-oxide, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein:
X represents —O—, —S— or —NR 3 —;
R 1 represents hydrogen, hydroxy, C 1-6 alkyl or aryl;
R 2 represents hydrogen; C 1-12 alkyl; C 3-7 cycloalkyl; C 2-8 alkenyl; aryl; Het 1 ; or C 1-12 alkyl substituted with one or two substituents selected from C 3-7 cycloalkyl, hydroxy, C 1-4 alkyloxy, cyano, amino, mono- and di(C 1-4 alkyl)amino, mono- or di(arylC 1-4 alkyl)amino, di(arylC 1-4 alkyl)aminocarbonyloxy, (C 1-4 alkyl) (arylC 1-4 alkyl)amino, mono- and di(aryl)amino, (C 1-4 alkyl)(di(C 1-4 alkyl)-aminoC 1-4 alkyl)amino, pyrrolidinyl, piperidinyl, piperazinyl optionally substituted with C 1-4 alkyl, morpholinyl, perhydro-azepinyl, carboxyl, C 1-4 alkyloxycarbonyl, aminocarbonyl, mono- and di(C 1-4 alkyl)aminocarbonyl, aryl, aryloxy and arylthio;
R 3 represents hydrogen, C 1-6 alkyl, aryl, Het 1 or C 1-6 alkyl substituted with aryl or Het 1 ;
R 4 represents hydrogen; hydroxy; mercapto; C 1-6 alkyloxy; C 1-6 alkylthio; aryloxy; arylthio; Het 1 -oxy; Het 1 -thio, C 1-12 alkyl; C 1-12 alkyl substituted with halo; C 2-8 alkenyl substituted with one, two or three substituents selected from aryl; or
—NR 3 R 5 . 9 (ii)
wherein R 5 represents hydrogen, C 1-6 alkyl, aryl, Het 1 , (aryl or Het 1 )C 1-6 alkyl, (aryl or Het 1 )carbonyl or (aryl or Het 1 )C 1-6 alkyloxycarbonyl;
aryl represents indanyl, indenyl, naphtyl, 5,6,7,8-tetrahydro-2-naphtalenyl, phenyl; said indanyl, indenyl, naphtyl or phenyl may be substituted with one, two, three, four or five substituents each independently selected from hydroxy, halo, nitro, cyano, amino, azido, mono- or di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylamino, C 1-6 alkyl, polyhaloC 1-6 alkyl, hydroxyC 1-6 alkyl, phenyl, phenyloxy, phenylC 1-6 alkyloxy, pyridinylC 1-6 alkyloxy, C 1-6 alkyloxy, formyl, carboxyl and C 1-6 alkylcarbonyl; or two adjacent carbon atoms on said phenyl may be substituted by a single bivalent radical having the formula C 1-12 alkanediyl or polyhaloC 1-12 alkanediyl;
Het represents an unsaturated heterocycle selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, and tetrazolyl; each of said unsaturated heterocycles may optionally be substituted with amino, mercapto, C 1-6 alkyl, C 1-6 alkylthio or aryl; and
Het 1 represents a monocyclic heterocycle selected from pyrrolidinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,3,4-triazolyl, 1,2,4-triazolyl, tetrahydrofuranyl, furanyl, thiolanyl, thienyl, dioxolanyl, isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, isoxazolidinyl, oxazolidinyl, isothiazolidinyl, thiazolidinyl, piperidinyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, tetrahydropyranyl, pyranyl, morpholinyl and dioxanyl; each of said monocyclic heterocycles may be optionally substituted with one or two substituents each independently selected from C 1-4 alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C 1-4 alkyloxycarbonyl; or a bicyclic heterocycle selected from indolinyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzofuranyl, benzothienyl, 2H-1-benzopyranyl, 3,4-dihydro-2H-1-benzopyranyl, benzthiazolyl, isoquinolinyl, quinolinyl, 3,4-dihydroquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, chromanyl, 1,4-benzodioxinyl, 1,4-benzoxathianyl, benzodioxanyl and benzodioxolanyl; each of said bicyclic heterocycles may be substituted with one or two substituents each independently selected from C 1-4 alkyl, hydroxy, amino, halo, aryl, arylcarbonyl or C 1-4 alkyloxycarbonyl;
with the proviso that N-[4-(imidazol-1-yl phenyl-methyl)-phenyl]-3-phenyl-acrylamide, N-[4-(1-imidazol-1-yl 2-methyl-propyl)-phenyl]-3-phenyl-acrylamide, N-[4-[(3-chloro-phenyl)-imidazol-1-yl-methyl]-phenyl]-3-phenyl-acrylamide, N-[4-[(3-fluoro-phenyl)-imidazol-1-yl-methyl]-phenyl]-3-phenyl-acrylamide, N-(4-imidazol-1-yl-methyl-phenyl)-3-phenyl-acrylamide, N-[4-(imidazol-1-yl phenyl-methyl)-phenyl]-3,3-diphenyl-acrylamide, N-[4-[1-(H-imidazol-1-yl)-ethyl]-phenyl]-formamide, 1-benzoyl-3-[4-(1-imidazol-1-yl-2-methyl-propyl)-phenyl]-thiourea, [4-(1-imidazol-1-yl-2-methyl-propyl)-phenyl]-thiourea, N-[4-(2-ethyl-1-[1,2,4]triazol-1-yl-butyl)-phenyl]-acetamide, and [4-(2-ethyl-1-imidazol-1-yl-butyl)-phenyl]-thiourea are not included.
16 . A compound as claimed in claim 15 wherein R 1 represents hydrogen, hydroxy or C 1-6 alkyl; and R 2 represents hydrogen; C 1-12 alkyl; C 3-7 cycloalkyl; C 2-8 alkenyl; aryl; Het 1 ; or C 1-12 alkyl substituted with one or two substituents selected from hydroxy, C 1-4 alkyloxy, cyano, mono- and di(C 1-4 alkyl)amino, mono- or di(arylC 1-4 alkyl)amino, di(arylC 1-4 alkyl)aminocarbonyloxy, (C 1-4 alkyl) (arylC 1-4 alkyl)amino, (C 1-4 alkyl)(di(C 1-4 alkyl)aminoC 1-4 alkyl)amino, piperidinyl, piperazinyl optionally substituted with C 1-4 alkyl, morpholinyl, C 1-4 alkyloxycarbonyl, aryl, aryloxy and arylthio.
17 . A compound as claimed in claim 16 wherein R 3 is hydrogen; X is O and R 4 is C 1-12 alkyl; C 1-12 alkyl optionally substituted with one, two or three substituents each independently selected from halo; or a radical of formula (ii).
18 . A compound as claimed in claim 16 wherein R 3 is hydrogen, X is S and R 4 is a radical of formula (ii).
19 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 15 .
20 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 15 .
21 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof, and (b) an effective amount of a compound of formula (I) as claimed in claim 15 .
22 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound of formula (I) as claimed in claim 15 .
23 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 15 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
24 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 15 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
25 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 15 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
26 . A method of treating a disorder selected from the group consisting of an oncology disorder and a keratinization disorder in a warm-blooded animal in need thereof comprising administering to the warm-blooded animal an effective amount of a compound of formula (I) as claimed in claim 15 .
27 . A compound selected from the group consisting of compounds of the formula
wherein
X is N; R 4 is CH 3 ;
X is N; R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form;
X is N; R 4 is OC 6 H 5 ;
X is N; R 4 is CH 2 Cl;
X is CH; R 4 is H;
X is CH; R 4 is CH 2 Cl;
X is CH; R 4 is OC 6 H 5 ;
X is N; R 4 is 2-benzothiazolyl-NH—; and
X is CH; R 4 is 2-benzothiazolyl-NH—.
28 . A compound selected from the group consisting of compounds of the formula
wherein
X is N, R 4 is CH 3 ;
X is N, R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form;
X is N, R 4 is CH═CHC 6 H 5 , in the (E) form;
X is N, R 4 is C(CH 3 )═CH(3-Cl—C 6 H 4 ), in the (E) form;
X is N, R 4 is C(CH 3 )═CH(4-F—C 6 H 4 ), in the (E) form;
X is N, R 4 is C(CH 3 )═CH(4-pyridinyl), in the (E) form;
X is N, R 4 is C(CH 3 )═CH(4-CF 3 —C 6 H 4 ), in the (E) form;
X is N, R 4 is CF═CHC 6 H 5 , in the (Z) form;
X is CH, R 4 is C 2 H 5 ;
X is CH, R 4 is C(CH 3 )═C(C 6 H 5 ) (3-pyridinyl), in the (E+Z) forms;
X is CH, R 4 is C(CH 3 )═C(C 6 H 5 )(CH 3 ), in the (E) form;
X is CH, R 4 is H;
X is CH, R 4 is OC 2 H 5 ;
X is CH, R 4 is (CH 2 ) 2 CH 2 Cl;
X is CH, R 4 is C═C(C 6 H 5 );
X is CH, R 4 is C(CH 3 )═C(C 6 H 5 )—C 2 H 5 , in the (Z) form;
X is CH, R 4 is OC 6 H 5 ;
X is CH, R 4 is C(CH 3 )═C(C 6 H 5 )(2-furanyl), in the (E) form;
X is CH, R 4 is CH(CH 3 )CH 3 ;
X is CH, R 4 is CH 3 , the (A) isomer thereof,
X is CH, R 4 is CH 3 , the (B) isomer thereof,
X is CH, R 4 is N(CH 3 )—CH 2 —C 6 H 5 ;
X is CH, R 4 is NH 2 ;
X is CH, R 4 is NH—CH 3 ;
X is CH, R 4 is NH—C(CH 3 ) 2 ;
X is CH, R 4 is NH—CH 2 —C 6 H 5 ;
X is CH, R 4 is NH-(3-pyridinyl);
X is CH, R 4 is NH-(2-pyrazinyl);
X is CH, R 4 is NH-(1-naphtalenyl);
X is CH, R 4 is NH—CH 2 -(4-Cl—C 6 H 4 );
X is CH, R 4 is NH-(2-pyridinyl);
X is CH, R 4 is NH-(4-pyridinyl);
X is CH, R 4 is NH-(6-benzodioxanyl); and
X is CH, R 4 is NH-(1-CH 3 -2-benzimidazolyl).
29 . A compound selected from the group consisting of compounds of the formula
wherein
X is N, R 4 is OC 6 H 5 , the (A) isomer thereof,
X is N, R 4 is H, the (B) isomer thereof,
X is N, R 4 is C(CH 3 )═CH(C 6 H 5 ), the B isomer of the (E) form thereof,
X is N, R 4 is OC 6 H 5 , the (B) isomer thereof,
X is N, R 4 is H, the (A) isomer thereof,
X is CH, R 4 is OC 6 H 5 , the (A) isomer thereof,
X is CH, R 4 is OC 6 H 5 ; and
X is CH, R 4 is H, the (A) isomer thereof.
30 . A compound selected from the group consisting of compounds of the formula
wherein
X is CH, R 1 is CH(CH 3 ) 2 , R 3 is CH 3 , R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form;
X is CH, R 1 is CH(CH 3 ) 2 , R 3 is C 2 H 5 , R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form; and
X is CH, R 1 is CH 2 [N(CH 3 ) 2 ], R 3 is H, R 4 is OC 6 H 5 .
31 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is 4-Cl—C 6 H 4 , R 6 is H;
R 1 is 3-Cl—C 6 H 4 , R 6 is H;
R 1 is 3-F—C 6 H 4 , R 6 is H;
R 1 is 4-F—C 6 H 4 , R 6 is H;
R 1 is C 6 H 5 , R 6 is C 6 H 5 ;
R 1 is C 6 H 5 , R 6 is CH 3 ;
R 1 is 4-F—C 6 H 4 , R 6 is CH 3 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is C 6 H 5 ;
R 1 is 3-Cl—C 6 H 4 , R 6 is CH 3 ;
R 1 is 3-Cl—C 6 H 4 , R 6 is C 6 H 5 ;
R 1 is 4-F—C 6 H 4 , R 6 is C 6 H 5 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is CH 3 ;
R 1 is C 6 H 5 , R 6 is C 2 H 5 ;
R 1 is C 6 H 5 , R 6 is C 3 H 7 ;
R 1 is CH(CH 3 ) 2 , R 6 is C 6 H 5 ;
R 1 is CH(CH 3 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is CH(CH 3 ) 2 , R 6 is 2-CH 3 —C 6 H 4 ;
R 1 is CH(CH 3 ) 2 , R 6 is C 2 H 5 ;
R 1 is CH(CH 3 ) 2 , R 6 is CH 3 , the isomer of the (E) form thereof;
R 1 is CH(CH 3 ) 2 , R 6 is CH 3 , the (−) isomer of the (E) form thereof;
R 1 is C 2 H 5 , R 6 is CH 3 , in the (E) form;
R 1 is C 4 H 9 , R 6 is CH 3 , in the (E) form;
R 1 is cyclohexyl, R 6 is CH 3 , in the (E) form;
R 1 is CH(CH 3 ) 2 , R 6 is C 3 H 7 , in the (E) form;
R 1 is CH(CH 3 ) 2 , R 6 is C 4 H 9 , in the (E) form;
R 1 is CH 3 , R 6 is CH 3 , in the (E) form;
R 1 is C 3 H 7 , R 6 is CH 3 , in the (E) form;
R 1 is cyclohexyl, R 6 is C 6 H 5 , in the (E) form;
R 1 is cyclopropyl, R 6 is CH 3 , in the (E) form;
R 1 is cyclopentyl, R 6 is CH 3 , in the (E) form;
R 1 is CH(CH 3 ) 2 , R 6 is CH(CH 3 ) 2 , in the (E) form;
R 1 is CH(CH 3 ) 2 , R 6 is cyclopentyl, in the (E) form;
R 1 is CH(CH 3 ) 2 ; R 6 is cyclohexyl, in the (E) form;
R 1 is CH 2 CH(CH 3 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is (CH 2 ) 2 CH(CH 3 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is CH 2 C(CH 3 ) 3 , R 6 is CH 3 , in the (E) form, the hydrate (2:1) thereof;
R 1 is 1,3-dioxan-5-yl, R 6 is CH 3 , in the (E) form;
R 1 is CH(C 2 H 5 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is CH═CH—CH(CH 3 ) 2 , R 6 is CH 3 , in the (E,E) form;
R 1 is CH(CH 3 )C 2 H 5 , R 6 is CH 3 , in the (E) form;
R 1 is C(CH 3 ) 3 , R 6 is CH 3 , in the (E) form;
R 1 is CH(CH 3 )C 3 H 7 , R 6 is CH 3 , the (A) isomer of the (E) form thereof;
R 1 is CH(S—C 6 H 5 )CH 3 , R 6 is CH 3 , the (A) isomer thereof;
R 1 is CH(S—C 6 H 5 )CH 3 , R 6 is CH 3 , the (B) isomer thereof;
R 1 is CH(C 6 H 5 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is CH(C 3 H 7 ) 2 , R 6 is CH 3 , in the (E) form;
R 1 is CH(CH 3 )C 5 H 11 , R 6 is CH 3 , in the (A) isomer of the (E) form thereof;
R 1 is CH(CH 3 )C 5 H 11 , R 6 is CH 3 , in the (B) isomer of the (E) form thereof;
R 1 is CH(C 6 H 5 )CH 3 , R 6 is CH 3 , in the (A) isomer of the (E) form thereof;
R 1 is CH(C 6 H 5 )CH 3 , R 6 is CH 3 , in the (B) isomer of the (E) form thereof;
R 1 is 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtalenyl, R 6 is CH 3 , in the (E) form;
R 1 is CH(C 2 H 5 )C 5 H 11 , R 6 is CH 3 , in the (A) isomer of the (E) form thereof;
R 1 is CH(C 2 H 5 )C 4 H 9 , R 6 is CH 3 , in the (E) form;
R 1 is CH(C 2 H 5 )C 5 H 11 , R 6 is CH 3 , the (B) isomer of the (E) form thereof,
R 1 is CH[N(CH 3 ) 2 ]CH 3 , R 6 is CH 3 , the (A) isomer of the (E) form thereof;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , R 6 is CH 3 , the (B) isomer of the (E) form thereof;
R 1 is C 6 H 5 , R 6 is H;
R 1 is H, R 6 is H;
R 1 is CH(CH 3 ) 2 , R 6 is H;
R 1 is 4-Br—C 6 H 4 , R 6 is H;
R 1 is 4-CH 3 —C 6 H 4 , R 6 is H;
R 1 is CH(CH 3 ) 2 , R 6 is H, in the (E) form; and
R 1 is 2,5-diCl—C 6 H 3 , R 6 is CH 3 , in the (E) form.
32 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is C 6 H 5 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is 3-Cl—C 6 H 4 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is 4-F—C 6 H 4 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is C 2 H 5 ;
R 1 is 4-F—C 6 H 4 , R 6 is H, R 7 is CH 3 ;
R 1 is H, R 6 is H, R 7 is C 6 H 5 ;
R 1 is CH 3 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is CH(CH 3 ) 2 , R 6 is H, R 7 is C 6 H 5 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is CH 3 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is C 4 H 9 ;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is cyclohexyl, the (E+Z) forms thereof;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is CH(CH 3 ) 2 , the (E+Z) forms thereof;
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is 3-pyridinyl;
R 1 is 4-F—C 6 H 4 , R 6 is H, R 7 is 3-pyridinyl;
R 1 is CH(CH 3 ) 2 , R 6 is CH 3 , R 7 is 3-thienyl, the (E+Z) forms thereof;
R 1 is CH(CH 3 ) 2 , R 6 is CH 3 , R 7 is C 3 H 7 , the (E+Z) forms thereof, and
R 1 is 4-Cl—C 6 H 4 , R 6 is H, R 7 is 3,5-diCl—C 6 H 3 .
33 . A compound selected from the group consisting of compounds of the formula
wherein;
R 1 is CH(CH 3 ) 2 ;
R 1 is 3-Cl—C 6 H 4 ;
R 1 is 3-F—C 6 H 4 ;
R 1 is 3-CF 3 —C 6 H 4 ;
R 1 is cyclohexyl;
R 1 is cyclopropyl;
R 1 is cyclopentyl;
R 1 is (CH 2 ) 2 CH(CH 3 ) 2 ;
R 1 is CH 2 C(CH 3 ) 3 ;
R 1 is 1,3-dioxan-5-yl;
R 1 is CH(C 2 H 5 ) 2 ;
R 1 is CH 2 N(CH 3 ) 2 ;
R 1 is CH(C 2 H 5 )(n-C 4 H 9 );
R 1 is 1-(ethoxycarbonyl)ethyl;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , the (A) isomer, the hydrate (1:1) thereof;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , the (B) isomer thereof;
R 1 is CH(CH 3 )[CH 2 (C 6 H 5 )];
R 1 is CH[N(C 2 H 5 ) 2 ]CH 3 , the (A) isomer thereof;
R 1 is CH[N(C 2 H 5 ) 2 ]CH 3 , the (B) isomer thereof;
R 1 is CH[N(C 2 H 5 ) 2 ]CH 3 ;
R 1 is CH[N(CH 3 ) 2 ]C 2 H 5 , the (A) isomer thereof;
R 1 is CH[N(CH 3 ) 2 ]C 2 H 5 , the (B) isomer thereof;
R 1 is CH═CH—CH(CH 3 ) 2 ;
R 1 is CH(CH 3 )C 2 H 5 ;
R 1 is C(CH 3 ) 3 ;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , the hydrate (1:1) thereof;
R 1 is CH(CH 3 )(n-C 3 H 7 );
R 1 is 1-(1-piperidinyl)ethyl;
R 1 is CH(S—C 6 H 5 )CH 3 , the (A+B) isomers thereof;
R 1 is CH(O—C 6 H 5 )CH 3 ;
R 1 is CH(CH 3 )CH 2 CN;
R 1 is CH(C 6 H 5 ) 2 ;
R 1 is CH(C 2 H 5 )(n-C 3 H 7 );
R 1 is CH(n-C 3 H 7 ) 2 ;
R 1 is CH(C 6 H 5 )CH 3 ;
R 1 is 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphtalenyl;
R 1 is CH(CH 3 )(n-C 5 H 11 );
R 1 is CH(C 2 H 5 )(n-C 5 H 11 );
R 1 is CH[N(CH 3 ) 2 ]C 2 H 5 ;
R 1 is (ethoxycarbonyl)methyl;
R 1 is CH[N(CH 3 )(CH 2 —C 6 H 5 )]CH 3 ;
R 1 is CH[N(CH 3 )(n-C 4 H 9 )]CH 3 ;
R 1 is CH[N(CH 3 )[(CH 2 ) 2 N(CH 3 ) 2 ]]CH 3 ;
R 1 is 1-(4-morpholinyl)ethyl;
R 1 is CH[N(CH 3 ) 2 ]C 2 H 5 ;
R 1 is CH[N(CH 3 )(C 2 H 5 )]CH 3 ;
R 1 is 1-methyl-3-piperidinyl
R 1 is 1-methyl-2-piperidinyl, the (A) isomer thereof;
R 1 is 1-(4-methyl-1-piperazinyl)ethyl;
R 1 is CH[N(CH 3 )(n-C 3 H 7 )]CH 3 ;
R 1 is CH[N(CH 3 )(C 2 H 5 —C 6 H 5 )]CH 3 ;
R 1 is CH[N(CH 2 —C 6 H 5 ) 2 ]CH 3
R 1 is CH[OC(═O)N(CH 2 —C 6 H 5 ) 2 ]CH 3 ; and
R 1 is 2,5-diCl—C 6 H 3 .
34 . A compound selected from the group consisting of compounds of the formula
wherein
R 7 is 3-Cl—C 6 H 4 , in the (E) form;
R 7 is 3-CF 3 —C 6 H 4 ;
R 7 is 4-Cl—C 6 H 4 , in the (E) form;
R 7 is 4-CF 3 —C 6 H 4 , in the (E) form;
R 7 is 4-OCH 3 —C 6 H 4 , in the (E) form;
R 7 is 4-F—C 6 H 4 , in the (E) form;
R 7 is 3-OCH 3 —C 6 H 4 , in the (E) form;
R 7 is 2-F—C 6 H 4 , in the (E) form;
R 7 is 3-F—C 6 H 4 , in the (E) form;
R 7 is (CH 2 ) 2 C 6 H 5 , in the (E) form;
R 7 is CH 2 C 6 H 5 , in the (E) form;
R 7 is 2-naphtalenyl, in the (E) form;
R 7 is 1-naphtalenyl, in the (E) form;
R 7 is 2,3,5,6-tetra(F)-4-(OC 2 H 5 )phenyl, in the (E) form;
R 7 is 2,4-di(F)—C 6 H 3 , in the (E) form;
R 7 is 3-Br-4-F—C 6 H 3 , in the (E) form;
R 7 is 2-F-4-CF 3 —C 6 H 3 , in the (E) form;
R 7 is 4-NO 2 —C 6 H 4 , in the (E) form;
R 7 is 4-NH 2 —C 6 H 4 , in the (E) form; and
R 7 is 4-(NHC(═O)CH 3 )—C 6 H 4 , in the (E) form.
35 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is 3-CF 3 —C 6 H 4 , R 4 is CH 3 ;
R 1 is 3-F—C 6 H 4 , R 4 is CH 3 ;
R 1 is 3-F—C 6 H 4 , R 4 is CH 3 ;
R 1 is 3-CF 3 —C 6 H 4 , R 4 is CH═CHC 6 H 5 , in the (E) form;
R 1 is 3-F—C 6 H 4 , R 4 is CH═CHC 6 H 5 , in the (E) form;
R 1 is 3-F—C 6 H 4 , R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form, the nitrate (1:1) salt thereof;
R 1 is CH 2 C(CH 3 ) 3 , R 4 is CH 3 ;
R 1 is CH(CH 3 )C 2 H 5 , R 4 is CH 3 ;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , R 4 is CH 3 , the (A) isomer thereof;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , R 4 is CH 3 , the (B) isomer thereof;
R 1 is CH[N(CH 3 ) 2 ]CH 3 , R 4 is C(CH 3 )═CHC 6 H 5 , in the (E) form;
R 1 is CH(CH 3 )CH 2 C 6 H 5 , R 4 is CH 3 ;
R 1 is 1-(methyl-1-piperidinyl)ethyl, R 4 is CH 3 ;
R 1 is CH(CH 3 )(n-C 3 H 7 ), R 4 is CH 3 ;
R 1 is C(CH 3 ) 3 , R 4 is CH 3 ;
R 1 is CH(n-C 3 H 7 ) 2 , R 4 is CH 3 ;
R 1 is CH(n-C 3 H 7 ) 2 , R 4 is CH 2 (3,4-diOCH 3 —C 6 H 3 );
R 1 is CH[N(CH 3 ) 2 ]C 2 H 5 , R 4 is CH 3 , the (A) isomer thereof;
R 1 is CH[N(C 2 H 5 ) 2 ]CH 3 , R 4 is CH 3 , the (A) isomer thereof; and
R 1 is CH[N(C 2 H 5 ) 2 ]CH 3 , R 4 is CH 3 , the (A+B) isomers thereof.
36 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is 4-Cl—C 6 H 4 , R 4 is CH═C(C 6 H 5 )(3-Cl—C 6 H 4 ), and wherein the methyl is on the 5 position of the imidazole, the (E+Z) forms thereof; and
R 1 is CH(CH 3 ) 2 , R 4 is CH 3 , and wherein the methyl is on the 2 position of the imidazole.
37 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is CH(CH 3 ) 2 , R 4 is CH 3 , X is CH;
R 1 is CH(CH 3 ) 2 , R 4 is C 6 H 5 , X is CH;
R 1 is CH(CH 3 ) 2 , R 4 is C 6 H 5 —C(═O)—, X is CH;
R 1 is CH(CH 3 ) 2 , R 4 is H, X is CH;
R 1 is CH(CH 3 ) 2 , R 4 is 2F—C 6 H 4 , X is CH;
R 1 is CH(CH 3 ) 2 , R 4 is 3F—C 6 H 4 , X is CH;
R 1 is CH(C 2 H 5 ) 2 , R 4 is C 6 H 5 —C(═O)—, X is CH;
R 1 is CH(C 2 H 5 ) 2 , R 4 is H, X is CH;
R 1 is CH(CH 3 )[N(CH 3 ) 2 ], R 4 is 2-benzothiazolyl, X is CH, the (A) isomer thereof;
R 1 is CH(C 2 H 5 ) 2 , R 4 is 2-benzothiazolyl, X is CH;
R 1 is CH(C 2 H 5 ) 2 , R 4 is 2-benzothiazolyl, X is N;
R 1 is 2,5-diCl—C 6 H 3 , R 4 is C 6 H 5 —C(═O)—, X is CH; and
R 1 is 2,5-diCl—C 6 H 3 , R 4 is H, X is CH.
38 . A compound selected from the group consisting of compounds of the formula
wherein
(R a ) n is 4-(O—C 2 H 5 ), R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 2,5-di(F), R 1 is 3-(CF 3 )—C 6 H 4 , X is CH;
(R a ) n is 2,5-di(F), R 1 is CH(C 2 H 5 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is 3-(CF 3 )—C 6 H 4 , X is N;
(R a ) n is 2,5-di(F), R 1 is CH(C 2 H 5 ) 2 , X is N;
(R a ) n is 2-F, R 1 is CH(C 2 H 5 ) 2 , X is CH;
(R a ) n is 2-F, R 1 is 3-(CF 3 )—C 6 H 4 , X is CH;
(R a ) n is 2-F, R 1 is CH(C 2 H 5 ) 2 , X is N;
(R a ) n is 4-OCH 3 , R 1 is 3-(CF 3 )—C 6 H 4 , X is CH;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH(CH 3 )[N(CH 3 ) 2 ], X is N, the (A) isomer thereof;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH(C 2 H 5 ) 2 , X is N;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH(CH 3 )[N(CH 3 ) 2 ], X is CH, the (A) isomer thereof;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH(CH 3 )[N(CH 3 ) 2 ], X is N, the (B) isomer thereof;
(R a ) n is 3,4-di(OCH 3 ), R 1 is CH 2 —N(CH 3 ) 2 , X is CH;
(R a ) n is 4-OCH 3 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is CH(C 2 H 5 ) 2 , X is N;
(R a ) n is 3-F, R 1 is CH(C 2 H 5 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is CH(CH 3 ) 2 , X is N;
(R a ) n is 2-F, R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-NH 2 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 2,5-di(F), R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is 3-(CF 3 )—C 6 H 4 , X is CH;
(R a ) n is 3-CF 3 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is 4-C 1 -C 6 H 4 , X is CH;
(R a ) n is 3,4-di(Cl), R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-OCH 3 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 2,4-di(F), R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is C 6 H 5 , X is CH;
(R a ) n is 3-CH 3 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-NO 2 , R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-Cl, R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 4-Cl, R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 4-F, R 1 is CH(CH 3 ) 2 , X is CH;
(R a ) n is 3-F, R 1 is CH(CH 3 ) 2 , X is CH; and
(R a ) n is H, R 1 is CH(CH 3 ) 2 , X is CH.
39 . A compound selected from the group consisting of compounds of the formula
wherein
R 1 is CH(CH 3 ) 2 , R 2 is H, NH 2 , X is N—C 6 H 5 , Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is H, NH 2 , X is N-(3F—C 6 H 4 ), Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is CH(CH 3 ) 2 , —CH 2 -(4-C 1 -C 6 H 4 ), X is O, Het is 1,2,4-triazol-1-yl;
R 1 is CH(CH 3 ) 2 , R 2 is CH(CH 3 ) 2 , —NH-(3-F—C 6 H 4 ), X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is CH(CH 3 ) 2 , CH 3 , X is O, Het is 1,2,4-triazol-1-yl;
R 1 is CH(CH 3 ) 2 , R 2 is H, CH 3 , X is O, Het is 1,2,4-triazol-4-yl;
R 1 is CH(CH 3 ) 2 , R 2 is H, —C(CH 3 )═CH—C 6 H 5 , X is O, Het is 1,2,4-triazol-4-yl;
R 1 is CH(CH 3 ) 2 , R 2 is CH(CH 3 ) 2 , CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is CH(CH 3 ) 2 , —C(CH 3 )═CH—C 6 H 5 , X is O, Het is 1H-1-imidazolyl, in the (E) form;
R 1 is CH 3 , R 2 is CH 3 , CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH 3 , R 2 is CH 3 , —C(CH 3 )═CH—C 6 H 5 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is C 2 H 5 , CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is C 2 H 5 , R 2 is C 2 H 5 , CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(C 2 H 5 ) 2 , R 2 is CH(CH 3 ) 2 , R 4 is CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is C 2 H 5 , R 4 is —C(CH 3 )═CH—C 6 H 5 , X is O, Het is 1H-1-imidazolyl, in the (E) form;
R 1 is CH(CH 3 ) 2 , R 2 is CH 3 , R 4 is CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is n-C 4 H 9 , R 4 is CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is n-C 4 H 9 , R 4 is —C(CH 3 )═CH—C 6 H 5 , X is O. Het is 1H-1-imidazolyl, in the (E) form;
R 1 is CH(C 2 H 5 ) 2 , R 2 is n-C 3 H 7 , R 4 is CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is CH(C 2 H 5 ) 2 , R 2 is C 2 H 5 , R 4 is CH 3 , X is O, Het is 1H-1-imidazolyl;
R 1 is OH, R 2 is CH(CH 3 )—N(CH 3 ) 2 , R 4 is CH 3 , X is O, Het is 1-methyl-5-imidazolyl;
R 1 is OH, R 2 is CH(C 2 H 5 ) 2 , R 4 is CH 3 , X is O, Het is 1-methyl-5-imidazolyl;
R 1 is CH(CH 3 ) 2 , R 2 is H, R 4 is —NH-(3-F—C 6 H 4 ), X is O, Het is 2-methyl-1-imidazolyl;
R 1 is 4-C 1 -C 6 H 4 , R 2 is H, R 4 is H, X is O, Het is 1-methyl-5-imidazolyl;
R 1 is 2,5-diCl—C 6 H 3 , R 2 is H, R 4 is —S—CH 3 , X is NH, Het is 1H-1-imidazolyl; and
R 1 is 2,5-diCl—C 6 H 3 , R 2 is H, R 4 is —NH—CH 3 , X is NH, Het is 1H-1-imidazolyl, the HCl (1:2) salt thereof.
40 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 27 .
41 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 27 .
42 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 27 .
43 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 27 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
44 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 27 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
45 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 27 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
46 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 28 .
47 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 28 .
48 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 28 .
49 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 28 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
50 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 28 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
51 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 28 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
52 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 29 .
53 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 29 .
54 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 29 .
55 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 29 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
56 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 29 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
57 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 29 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
58 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 30 .
59 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 30 .
60 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 30 .
61 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 30 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
62 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 30 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
63 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 30 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
64 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 31 .
65 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 31 .
66 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 31 .
67 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 31 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
68 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 31 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
69 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 31 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
70 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 32 .
71 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 32 .
72 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 32 .
73 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 32 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
74 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 32 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
75 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 32 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
76 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 33 .
77 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 33 .
78 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 33 .
79 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 33 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
80 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 33 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
81 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 33 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
82 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 34 .
83 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 34 .
84 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 34 .
85 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 34 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
86 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 34 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
87 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 34 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
88 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 35 .
89 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 35 .
90 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 35 .
91 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 35 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
92 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 35 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
93 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 35 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
94 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 36 .
95 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 36 .
96 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 36 .
97 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 36 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
98 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 36 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
99 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 36 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
100 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 37 .
101 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 37 .
102 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 37 .
103 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 37 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
104 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 37 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
105 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 37 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
106 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 38 .
107 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 38 .
108 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 38 .
109 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 38 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
110 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 38 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
111 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 38 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
112 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 39 .
113 . A process of preparing a pharmaceutical composition comprising intimately mixing a pharmaceutically acceptable carrier with a therapeutically effective amount of a compound as claimed in claim 39 .
114 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredients (a) an effective amount of calcitriol or a prodrug thereof, and (b) an effective amount of a compound as claimed in claim 39 .
115 . A product containing (a) a pharmaceutical composition containing an effective amount of retinoic acid, a derivative thereof or a stereochemically isomeric form thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 39 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
116 . A product containing (a) a pharmaceutical composition containing an effective amount of calcitriol or a prodrug thereof and a pharmaceutical acceptable carrier, and (b) a pharmaceutical composition containing an effective amount of a compound of formula (I) as claimed in claim 39 , and a pharmaceutical acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.
117 . A product containing a) a pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in claim 39 and a pharmaceutically acceptable carrier; and b) a pharmaceutical composition comprising a pharmaceutically effective amount of an anti-neoplastic agent and a pharmaceutically acceptable carrier, as a combined preparation for simultaneous, separate or sequential use in dermatological or oncological disorders.Join the waitlist — get patent alerts
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