Patent EA-004299-B1 (EA)
Title: Monofluoroalkyl derivatives
Inventor: BENDER DAVID MICHAEL
IPC: C07D213/82
Filed: 2000-04-17
Abstract: 1. A compound of the formula: wherein: A represents SO2; R<A> represents (1-6C)alkyl; R<B> represents H, R<1> represents a naphthyl group or a phenyl, furyl, thienyl or pyridyl group which is unsubstituted or substituted by one or two substituents selected independently from halogen; nitro; cyano; hydroxyimino; (1-10C)alkyl; (2-10C)alkenyl; (2-10C)alkynyl; (3-8C)cycloalkyl; hydroxy(3-8C)cycloalkyl; oxo(3-8C)cycloalkyl; halo(1-10C)alkyl; (CH2)y X<1>R<9> in which y is 0 or an integer of from 1 to 4, X<1> represents O, S, NR<10>, CO, COO, OCO, CONR<11>, NR<12>CO, NR<12>COCOO or OCONR<13>, R<9> represents hydrogen, (1-10C)alkyl, (3-10C)alkenyl, (3-10C)alkynyl, pyrrolidinyl, tetrahydrofuryl, morpholino or (3-8C)cycloalkyl and R<10>, R<11>, R<12> and R<13> each independently represents hydrogen or (1-10C)alkyl, or R<9> and R<10>, R<11>, R<12> or R<13> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group; N-(1-4C)alkylpiperazinyl; N-phenyl(1-4C)alkylpiperazinyl; thienyl; furyl; oxazolyl; isoxazolyl; pyrazolyl; imidazolyl; thiazolyl; pyridyl; pyridazinyl; pyrimidinyl; dihydro-thienyl; dihydrofuryl; dihydrothiopyranyl; dihydropyranyl; dihydrothiazolyl; (1-4C)alkoxycarbonyldihydrothiazolyl; (1-4C)alkoxycarbonyldimethyldihydro-thiazolyl; tetrahydro-thienyl; tetrahydrofuryl; tetrahydrothiopyranyl; tetrahydropyranyl; indolyl; benzofuryl; benzothienyl; benzimidazolyl; and a group of formula R<14>-(L<A>)n-X<2>-(L<B>)m in which X<2> represents a bond, O, NH, S, SO, SO2, CO, CH(OH), CONH, NHCO, NHCONH, NHCOO, COCONH, OCH2CONH or CH=CH, L<A> and L<B> each represent (1-4C)alkylene, one of n and m is 0 or 1 and the other is 0, and R<14> represents a phenyl or heteroaromatic group which is unsubstituted or substituted by one or two of halogen, nitro, cyano, hydroxyimino, (1-10C) alkyl, (2-10C)alkenyl, (2-10C)alkynyl, (3-8C)-cycloalkyl, 4-(1,1-dioxotetrahydro-1,2-thiazinyl), halo(1-10C)alkyl, cyano(2-10C)alkenyl, phenyl, and (CH2)z X<3>R<15> in which z is 0 or an integer of from 1 to 4, X<3> represents O, S, NR<16>, CO, CH(OH), COO, OCO, CONR<17>, NR<18>CO, NHSO2, SO2NH, NHSO2NR<17>, NHCONH, OCONR19 or NR<19>COO, R<15> represents hydrogen, (1-10C)alkyl, phenyl(1-4C)alkyl, halo(1-10C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkylsulfonylamino(1-4C)alkyl, (N-(1-4C)alkoxycarbonyl)(1-4C)alkylsulfonylamino-(1-4C)alkyl, (3-10C)alkenyl, (3-10C)alkynyl, (3-8C)-cycloalkyl, camphoryl or an aromatic or heteroaromatic group which is unsubstituted or substituted by one or two of halogen, (1-4C)alkyl, halo(1-4C)alkyl, di(1-4C)alkylamino and (1-4C)alkoxy and R<16>, R<17>, R<18> and R<19> each independently represents hydrogen or (1-10C)alkyl, or R<15> and R<16>, R<17>, R<18> or R<19> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group. R<2> represents (1-6C)alkyl, or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1 wherein R<2> represents methyl, ethyl, isopropyl or tret-butyl. 3. A compound according to claim 2 wherein R<A> represents methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, pentyl or hexyl. 4. A compound according to claim 3 wherein R<A> represents methyl. 5. A compound according to claim 1 wherein R<2> represents isopropyl. 6. A compound as claimed in any one of claims 1 to 5 wherein R<1> is selected from the group consisting of: 7. A compound selected from the group consisting of: [2-fluoro-2-(4-iodophenyl)propyl] [(methylethyl)sulfonyl]amine; [2-fluoro-2-(4-phenylphenyl)propyl][(methylethyl)sulfonyl] amine; 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzenecarbonitrile; 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzoic acid; {2-[4-(3-aminophenyl)phenyl]-2-fluoropropyl}[(methylethyl)sulfonyl]amine; [2-fluoro-2-(4-{3-[(methylsulfonyl)amino]phenyl}phenyl)propyl][(methylethyl)sulfonyl]amine; [2-fluoro-2-(4-(3-thienyl)phenyl)propyl][(methylethyl)sulfonyl]amine; [2-fluoro-2-(4-(3-pyridyl)phenyl)propyl][(methylethyl)sulfonyl]amine; 2-{4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}ethanenitrile; 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzaldehyde; {4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}-N-methylcarboxamide; {4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}-N,N-dimethylcarboxamide; N-ethyl{4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}carboxamide; 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl pyrrolidinyl ketone; N-{3-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}acetamide; N-{3-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}propanamide; N-{3-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}butanamide; amino-N-{3-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}amide; N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzamide; (3-cyanophenyl)-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl] carboxamide; N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]-4-pyridylcarboxamide; N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]{4-[2-(methoxycarbonylamino)ethyl]phenyl}carboxamide; (2-{4-[(3,5-difluorophenyl)methoxy]phenyl}-2-fluoropropyl)[(methylethyl)sulfonyl]amine; {2-fluoro-2-[4-(4-{2-[(methylsulfonyl)amino]ethyl}phenyl)phenyl]propyl}[(methylethyl) sulfonyl]amine; (4-chlorophenyl)-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl] carboxamide; (6-chloro(3-pyridyl))-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl] carboxamide; (4-cyanophenyl)-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl] carboxamide; ethoxy-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]carboxamide; N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]isoxazol-5-yl-carboxamide; 4-(dimethylamino)-N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl] butanamide; N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]-3-thienylcarboxamide; {2-fluoro-2-[4-(phenylmethoxy)phenyl]propyl}[(methylethyl)sulfonyl]amine; 2-{[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenoxy]methyl} benzenecarbonitrile; [2-fluoro-2-(4-methoxyphenyl)propyl][(methylethyl)sulfonyl]amine; {2-[4-(3,5-difluorophenyl)phenyl]-2-fluoropropyl}[(methylethyl)sulfonyl]amine; [(dimethylamino)sulfonyl][2-fluoro-2-(4-iodophenyl)propyl]amine; 4-[4-(2-{[(dimethylamino)sulfonyl]amino}-1-fluoro-isopropyl)phenyl]benzenecarbonitrile; [(dimethylamino)sulfonyl][2-fluoro-2-(4-{3-[(methylsulfonyl)amino]phenyl}phenyl) propyl]amine; [(dimethylamino)sulfonyl]{2-fluoro-2-[4-(3-{[(methylethyl)sulfonyl]amino}phenyl)phenyl] propyl}amine; 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzenesulfonamide; N-(2-{3-fluoro-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-yl}-ethyl)-isobutyramide; N-(2-{3-fluoro-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-yl}-ethyl)-acetamide; N-{2-(2-fluoro-2-[3'-fluoro-4'-(2-methanesulfonylamino)-ethyl)-biphenyl-4-yl]propyl}-2-propane sulfonamide; N-{2-(2-fluoro-2-[3'-fluoro-4'-(2-(propane-2-sulfonylamino)-ethyl)-biphenyl-4-yl]propyl}-2-propane sulfonamide; N-(2-{3'-fluoro-4'-[2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-yl}-2-hydroxy-propyl)-2-propane sulfonamide; N-{2-Fluoro-2-[4-(2-oxo-2,3-dihydro-1H-indol-6-yl)-phenyl]-propyl)-2-propanesulfonamide; (+)-[2-fluoro-2-(4-iodophenyl)propyl][(methylethyl)sulfonyl]amine; (-)-[2-fluoro-2-(4-iodophenyl)propyl][(methylethyl)sulfonyl]amine; [2-fluoro-2-(4-{3-[(methylsulfonyl)amino]phenyl}phenyl)propyl][(methylethyl)sulfonyl]amine (enantiomer 1); [2-fluoro-2-(4-{3-[(methylsulfonyl)amino]phenyl}phenyl)propyl][(methylethyl)sulfonyl]amine (enantiomer 2); {4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}-N-methylcarboxamide (enantiomer 1); and {4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]phenyl}-N-methylcarboxamide (enantiomer 2); and the pharmaceutically acceptable salts thereof. 8. A compound according to claim 5 wherein the substituted phenyl is substituted with halogen; nitro; cyano; hydroxyimino; (1-10C) alkyl; (2-10C)alkenyl; (2-10C)alkynyl; (3-8C)cycloalkyl; hydroxy(3-8C)cycloalkyl; oxo(3-8C)cycloalkyl; halo(1-10C)alkyl; (CH2)y X<1>R<9> in which y is 0 or an integer of from 1 to 4, X<1> represents O, S, NR<10>, CO, COO, OCO, CONR<11>, NR<12>CO, NR<12>COCOO, OCONR<13>, R<9> represents hydrogen, (1-10C) alkyl, (3-10C)alkenyl, (3-10C)alkynyl, pyrrolidinyl, tetrahydrofuryl, morpholino or (3-8C)cycloalkyl and R<10>, R<11>, R<12> and R<13> each independently represents hydrogen or (1-10C)alkyl, or R<9> and R<10>, R<11>, R<12> or R<13> together with the nitrogen atom to which they are attached form an azetidinyl, pyrrolidinyl, piperidinyl or morpholino group; N-(1-4C)alkylpiperazinyl; N-phenyl(1-4C)alkylpiperazinyl; thienyl; furyl; oxazolyl; isoxazolyl; pyrazolyl; imidazolyl; thiazolyl; pyridyl; pyridazinyl; pyrimidinyl; dihydrothienyl; dihydrofuryl; dihydrothiopyranyl; dihydropyranyl; dihydrothiazolyl; (1-4C)alkoxycarbonyl dihydrothiazolyl; (1-4C)alkoxycarbonyl dimethyl-dihydrothiazolyl; tetrahydrothienyl; tetrahydrofuryl; tetrahydrothiopyranyl; tetrahydropyranyl; indolyl; benzofuryl; benzothienyl; benzimidazolyl; and a group of formula R<14>(L<A>)n-X<2>-(L<B>)m in which X<2> represents a bond, O, NH, S, SO, SO2, CO, CH(OH), CONH, NHCO, NHCONH, NHCOO, COCONH, OCH2CONH, or CH=CH, L<A> and L<B> each represent (1-4C)alkylene, one of n and m is 0 or 1 and the other is 0, and R<14> represents a phenyl or heteroaromatic group which is unsubstituted or substituted by one or two of halogen; nitro; cyano; (1-10C) alkyl