Patent EA-000898-B1 (EA)
Title: Isothiazolone derivatives, pharmaceutical acceptable salts and solvates thereof, pharmaceutical composition with anti-retroviral, anti-inflammatory and anti-atherosclerotic activity.
Inventor: BOLTON GARY LOUIS
IPC: A61K31/4439
Filed: 1996-04-26
Abstract: 1. Izothiazolone derivatives of general formula (I)   wherein  R<1> and R<2> independently are hydrogen, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted phenyl-(CR<6>R<7>)m -, substituted or unsubstituted Het(CR<6>R<7>)m, where Het is heterocycle, m is 0, 1 or 2-, C1-C6 alkoxy, hydroxy, cyano, NR<3>COR<4>, CO2R<3>, CONR<3>R<4>, S(O)mR<3>, sulfo group, S(O)mNR<3>R<4>, COR<3> or taken together are oxo group or methylenedioxy group; R<3> and R<4> independently are hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, Het(CR<6>R<7>)m-, or phenyl-(CR<6>R<7>)m-, wherein Het and m have values as defined above, R<5> is C1-C6 alkyl, C1-C6 acyl, C3-C6 cycloalkyl, substituted phenyl-(CR<6>R<7>)m-, unsubstituted or substituted Het(CR<6>R<7>)m-, wherein Het and m have values as defined above, wherein alkyl, acyl and cycloalkyl groups may optionally be substituted with from 1 to 3 groups selected from  NR<3>R<4>, NR<3>COR<4>, CO2R<3>, CONR<3>R<4>, S(O)mR<3>, sulfo group, S(O)mHNR<3>R<4>, or COR<3>; and phenyl and heterocyclic groups may be optionally substituted with halo, hydroxy, NR<3>R<4>,  NR<3>COR<4>, CO2R<3>, CONR<3>R<4>, S(O)mR<3>,sulfo group, S(O)mNR<3>R<4> or COR<3>; where R<3>, R<4>, Het and m have values as defined above, R<6> and R<7> independently are hydrogen, C1-C6 alkyl, CO2R<3>, hydroxy, CONR<3>R<4>, or cyano;  provided that R<5> is other than substituted phenyl-(CR<6>R<7>)m - when the substituent on the phenyl ring is alkyl, halo, alkoxy, or NR<3>R<4>; and the pharmaceutically acceptable salts and solvates thereof. 2. Izothiazolone derivatives of general formula (I) of claim 1 wherein R<5> is    3. Izothiazolone derivatives of general formula (I) of claim 2, where R<2> is hydrogen. 4. Izothiazolone derivatives of claim 3, where R<5> is    5. Izothiazolone derivatives of general formula (I) of claim 4, which is [S-(R*,R*)]-3-Methyl-2-(3-oxo-3H-benzo[d] isothiazol-2-yl)pentanoic acid;  2-(6-Methoxy-3-oxo-3h-benzo[d]isothiazol-2yl)-pentanoic acid;  (S)-4-Methyl-2-(5-fluoro-3-oxo-3h-benzo[d] isothiazol-2-yl)-pentanoic acid; and  (S)-4-Methyl-2-(6-methyl-3-oxo-3h-benzo[d] isothiazol-2-yl)-pentanoic acid. 6. Izothiazolone derivatives of general formula (I) of claim 3, where R<5> is   7. Izothiazolone derivatives of general formula (I) of claim 4 of claim 6 wherein R<3> is hydrogen. 8. Izothiazolone derivatives of general formula (I) of claim 7 which is N-Acetyl-4-(3-oxo-3h-benzo[d]isothiazol-2-yl)-benzenesulfonamide. 9. Izothiazolone derivatives of general formula (I) of claim 7 wherein R<4> is hydrogen. 10. Izothiazolone derivatives of claim 9 which is  4-(3-Oxo-3H-benzo[d]isothiazol-2-yl) benzenesulfonamide;  4-(5-Methoxy-3-oxo-3h -benzo[d]isothiazol-2-yl)-benzenesulfonamide;  4-(6-Methyl-3-oxo-3h-benzo[d]isothiazol-2-yl)-benzenesulfonamide;  4-(6-Fluoro-3-oxo-3h-benzo[d]isothiazol-2-yl)-benzenesulfonamide; and  4-(5-Methyl-3-oxo-3h-benzo[d]isothiazol-2-yl)-benzenesulfonamide. 11. A pharmaceutical composition having antiretroviral, antiinflammatory and antiatherosclerotic agents, comprising an active compound based on izothiazolone derivatives an on at least one pharmaceutically acceptable carrier, wherein as an izothiazolone derivative comprises a compund of general formula (I) of claim 1 or the pharmaceutically acceptable salt and solvates thereof in an effective amount. 12. A pharmaceutical composition of claim 11, wherein comprising a compound of formula as a izothiazolone derivative. 13. A pharmaceutical composition of claim 12, wherein comprising a compound where R<2> is hydrogen as a izothiazolone derivative. 14. A pharmaceutical composition of claim 13, wherein comprising as a izothiazolone derivative a compound where R<5> is    15. A pharmaceutical composition of claim 14, wherein comprising [S-(R*,R*)]-3-methyl-2-(3-oxo-3H-benzo[d]isothiazol-2-yl)pentanoic acid as a izothiazolone derivative. 16. A pharmaceutical composition of claim 14, wherein comprising 4-(3-oxo-3H-benzo[d]isothiazol-2-yl)-benzenesulfonamide as a izothiazolone derivative.