.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 8,080,551

« Back to Dashboard

Claims for Patent: 8,080,551

Title:HIV inhibiting pyrimidines derivatives
Abstract: HIV replication inhibitors having formula (I) defined herein are disclosed. Pharmaceutical compositions containing the HIV replication inhibitors; the use of the HIV replication inhibitors in the treatment of HIV; and processes for preparing the HIV replication inhibitors are also disclosed.
Inventor(s): Guillemont; Jerome Emile Georges (Andre, FR), Palandijian; Patrice (Louviers, FR), De Jonge; Marc Rene (Tilburg, NL), Koymans; Lucien Maria Henricus (Retie, BE), Vinkers; Hendrik Maarten (Antwerp, BE), Daeyaert; Frederik Frans Desire (Beerse, BE), Heeres; Jan (Vosselaar, BE), Van Aken; Koen Jeanne Alfons (Kortrijk, BE), Lewi; Paulus Joannes (Turnhout, BE), Janssen; Paul Adriaan Jan (Vosselaar, BE), Arts, legal representative; Frank Xavier Jozef Herwig (Beerse, BE)
Assignee: Janssen Pharmaceutica N.V. (BE)
Application Number:11/474,855
Patent Claims: 1. A compound of the following formula ##STR00254## a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine, or a stereochemically isomeric form thereof, wherein R.sup.1 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl, or C.sub.1-6alkylcarbonyloxy; or C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.2'is halo, C.sub.1-6alkyl, trihalomethyl, cyano, aminocarbonyl, or C.sub.1-6alkyl substituted with cyano or aminocarbonyl; each R.sup.2 independently is hydroxy, halo, C.sub.1-6alkyl optionally substituted with cyano or --C(.dbd.O)R.sup.6, C.sub.3-7cycloalkyl, C.sub.2-6alkenyl optionally substituted with one or more halogen atoms or cyano, C.sub.2-6alkynyl optionally substituted with one or more halogen atoms or cyano, C.sub.1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6alkyl)amino, polyhalomethyl, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6, or a radical of formula ##STR00255## wherein each A.sub.1 independently is N, CH or CR.sup.6; and A.sub.2 is NH, O, S or NR.sup.6; n' is 0, 1, 2, 3 or 4; X.sub.1 is --NR.sup.5--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, C.sub.1-4alkanediyl, --CHOH--, --S--, --S(.dbd.O).sub.p--, --X.sub.2--C.sub.1-4alkanediyl--, or --C.sub.1-4alkanediyl--X.sub.2--; X.sub.2 is --NR.sup.5--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--, --S--, or --S(.dbd.O).sub.p--; R.sup.3 is NHR.sup.13; NR.sup.13R.sup.14; --C(.dbd.O)--NHR.sup.13; --C(.dbd.O)--NR.sup.13R.sup.14; --C(.dbd.O)--R.sup.15; --CH.dbd.N--NH--C(.dbd.O)--R.sup.16; C.sub.1-6alkyl substituted with NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyl substituted with two or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyl substituted with one or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O) --NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7 and wherein 2 hydrogen atoms bound at the same carbon atom are replaced by C.sub.1-4alkanediyl; C.sub.1-6alkyl substituted with hydroxy and a second substituent selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyloxyC.sub.1-6alkyl optionally substituted with one or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.2-6alkenyl substituted with one or more substituents each independently selected from halo, cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.2-6alkynyl substituted with one or more substituents each independently selected from halo, cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; --C(.dbd.N--O--R.sup.8)--C.sub.1-4alkyl; R.sup.7 or --X.sub.3R.sup.7; with R.sup.9a representing hydroxy; C.sub.1-6alkyl; C.sub.1-6alkyloxy; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyloxycarbonyl; amino; mono- or di(C.sub.1-6alkyl)amino; mono- or di(C.sub.1-6alkyl)aminocarbonyl, --CH(.dbd.NR.sup.11) or R.sup.7, wherein each of the aforementioned C.sub.1-6alkyl groups in the definition of R.sup.9a may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-4alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6,--C(.dbd.NH)R.sup.6, R.sup.7; and wherein R.sup.9a may also be taken together with R.sup.10 to form a bivalent radical of formula (d-1), (d-2), (d-3), (d-4), (d-5) or (d-6) as defined for R.sup.9 and R.sup.10. X.sub.3 is --NR.sup.5--, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --S--, --S(.dbd.O).sub.p--, --X.sub.2--C.sub.1-4alkanediyl-, --C.sub.1-4alkanediyl-X.sub.2a--, --C.sub.1-4alkanediyl-X.sub.2b--C.sub.1-4alkanediyl, or --C(.dbd.N--OR.sup.8)--C.sub.1-4alkanediyl-; with X.sub.2a being --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --S--, or --S(.dbd.O).sub.p--; and with X.sub.2b being --NH--NH--, --N.dbd.N--, --C(.dbd.O)--, --S--, or --S(.dbd.O).sub.p--; R.sup.4 is halo, hydroxy, C.sub.1-6alkyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyl, formyl, amino, mono- or di(C.sub.1-4alkyl)amino, or R.sup.7; m is 0, 1, 2, 3 or 4; R.sup.5 is hydrogen; aryl; formyl; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyl; C.sub.1-6alkyloxycarbonyl; C.sub.1-6alkyl substituted with formyl, C.sub.1-6alkylcarbonyl, C.sub.1-6alkyloxycarbonyl or C.sub.1-6alkylcarbonyloxy; or C.sub.1-6alkyloxyC.sub.1-6alkylcarbonyl substituted with C.sub.1-6alkyloxycarbonyl; R.sup.6 is C.sub.1-4alkyl, amino, mono- or di(C.sub.1-4alkyl)amino, or polyhaloC.sub.1-4alkyl; R.sup.7is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic heterocycle, wherein each of said carbocyclic or heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, aminoC.sub.1-6alkyl, mono or di(C.sub.1-6alkyl)aminoC.sub.1-6alkyl, formyl, C.sub.1-6alkylcarbonyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylthio, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, --CH(.dbd.N--O--R.sup.8), R.sup.7a, --X.sub.3--R.sup.7a, and R.sup.7a--C.sub.1-4alkyl; R.sup.7a is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic heterocycle, wherein each of said carbocyclic or heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, aminoC.sub.1-6alkyl, mono or di(C.sub.1-6alkyl)aminoC.sub.1-6alkyl, formyl, C.sub.1-6alkylcarbonyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylthio, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, and --CH(.dbd.N--O--R.sup.8); R.sup.8 is hydrogen, C.sub.1-4alkyl, aryl, or arylC.sub.1-4alkyl; R.sup.9 and R.sup.10 each independently are hydrogen; hydroxy; C.sub.1-6alkyl; C.sub.1-6alkyloxy; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyloxycarbonyl; amino; mono- or di(C.sub.1-6alkyl)amino; mono- or di(C.sub.1-6alkyl)aminocarbonyl; --CH(.dbd.NR.sup.11); or R.sup.7; wherein each of the aforementioned C.sub.1-6alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di (C.sub.1-4alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6,--C(.dbd.NH)R.sup.6, and R.sup.7; or R.sup.9 and R.sup.10 may be taken together to form a bivalent radical of formula --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2-- (d-1), --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2-- (d-2), --CH.sub.2--CH.sub.2--O--CH.sub.2--CH.sub.2-- (d-3), --CH.sub.2--CH.sub.2--S--CH.sub.2--CH.sub.2-- (d-4), --CH.sub.2--CH.sub.2--NR.sup.12--CH.sub.2--CH.sub.2-- (d-5), --CH.sub.2--CH.dbd.CH--CH.sub.2-- (d-6); R.sup.11 is cyano; C.sub.1-4alkyl optionally substituted with C.sub.1-4alkyloxy, cyano, amino, mono- or di(C.sub.1-4alkyl)amino or aminocarbonyl; C.sub.1-4alkylcarbonyl; C.sub.1-4alkyloxycarbonyl; aminocarbonyl; or mono- or di(C.sub.1-4alkyl)aminocarbonyl; R.sup.12 is hydrogen or C.sub.1-4alkyl; R.sup.13 and R.sup.14 each independently are C.sub.1-6alkyl optionally substituted with cyano or aminocarbonyl, C.sub.2-6alkenyl optionally substituted with cyano or aminocarbonyl, or C.sub.2-6alkynyl optionally substituted with cyano or aminocarbonyl; R.sup.15is C.sub.1-6alkyl substituted with cyano or aminocarbonyl; R.sup.16 is C.sub.1-6alkyl optionally substituted with cyano or aminocarbonyl, or R.sup.7; p is 1 or 2; aryl is phenyl or phenyl substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, aminoC.sub.1-6alkyl, mono or di(C.sub.1-6alkyl)aminoC.sub.1-6alkyl, C.sub.1-6alkylcarbonyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylthio, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, R.sup.7, and --X.sub.3--R.sup.7.

2. A compound according to claim 1 wherein R.sup.3 is C.sub.1-6alkyl substituted with two or more substituents selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7; C.sub.1-6alkyl substituted with at least one substituent selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7 and wherein 2 hydrogen atoms bound at the same carbon atom are replaced by C.sub.1-4alkanediyl; C.sub.1-6alkyl substituted with hydroxy and a second substituent selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7; C.sub.1-6alkyloxyC.sub.1-6alkyl substituted with at least one substituent selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7; C.sub.2-6alkenyl substituted with at least one substituent selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7; C.sub.2-6alkynyl substituted with at least one substituent selected from cyano, aminocarbonyl, NR.sup.9R.sup.10 or R.sup.7; --C(.dbd.N--O--R )--C.sub.1-4alkyl; R.sup.7 or --X.sub.3--R.sup.7; R.sup.4 is halo, hydroxy, C.sub.1-6a1kyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylcarbonyl, formyl, amino, mono- or di(C.sub.1-4alkyl)amino; R.sup.7 is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic heterocycle, wherein each of said carbocyclic or heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, aminoC.sub.1-6alkyl, mono or di(C.sub.1-6alkyl)C.sub.1-6alkyl, C.sub.1-6alkylcarbonyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylthio, cyano, nitro, polyhaloC.sub.1-6alkyl, polyhaloC.sub.1-6alkyloxy, aminocarbonyl, R.sup.7a, --X.sub.3--R.sup.7a, and R.sup.7a--C.sub.1-4alkyl; R.sup.7a is a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic saturated, partially saturated or aromatic heterocycle, wherein each of said carbocyclic or heterocyclic ring systems may optionally be substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, aminoC.sub.1-6alkyl, mono or di(C.sub.1-6alkyl)aminoC.sub.1-6alkyl, C.sub.1-6alkylcarbonyl, C.sub.3-7cycloalkyl, C.sub.1-6alkyloxy, C.sub.1-6alkyloxycarbonyl, C.sub.1-6alkylthio, cyano, nitro, polyhalo C.sub.1-6alkyl, polyhalo C.sub.1-6alkyloxy or aminocarbonyl; R.sup.9 and R.sup.10 each independently are hydrogen; hydroxy; C.sub.1-6alkyl; C.sub.1-6alkyloxy; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyloxycarbonyl; amino; mono- or di(C.sub.1-6alkyl)amino; mono- or di(C.sub.1-6alkyl)aminocarbonyl, and R.sup.7, wherein each of the aforementioned C.sub.1-6alkyl groups may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxy C.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-4alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6,--C(.dbd.NH)R.sup.6, and R.sup.7.

3. A compound according to claim 1 wherein R.sup.2' is cyano, aminocarbonyl, or C.sub.1-6alkyl substituted with cyano or aminocarbonyl.

4. A pharmaceutical composition comprising as an active ingredient a compound as claimed in claim 1.

5. A process for preparing a pharmaceutical composition according to claim 4, comprising mixing a therapeutically effective amount of said compound with a pharmaceutically acceptable carrier.

6. A pharmaceutical composition according to claim 4, further comprising a pharmaceutically acceptable carrier.

7. A compound according to claim 1 wherein R.sup.3 is --CH.dbd.N--NH--C(.dbd.O)--R.sup.16; C.sub.1-6alkyl substituted with NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9aR.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyl substituted with two or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyl substituted with one or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7 and wherein 2 hydrogen atoms bound at the same carbon atom are replaced by C.sub.1-4alkanediyl; C.sub.1-6alkyl substituted with hydroxy and a second substituent selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.1-6alkyloxyC.sub.1-6alkyl optionally substituted with one or more substituents each independently selected from cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.2-6alkenyl substituted with one or more substituents each independently selected from halo, cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; C.sub.2-6alkynyl substituted with one or more substituents each independently selected from halo, cyano, NR.sup.9R.sup.10, --C(.dbd.O)--NR.sup.9R.sup.10, --C(.dbd.O)--C.sub.1-6alkyl or R.sup.7; --C(.dbd.N--O--R.sup.8)--C.sub.1-4alkyl; R.sup.7 or --X.sub.3--R.sup.7; with R.sup.9a representing hydroxy; C.sub.1-6alkyl; C.sub.1-6alkyloxy; C.sub.1-6alkylcarbonyl; C.sub.1-6alkyloxycarbonyl; amino; mono- or di(C.sub.1-6alkyl)amino; mono- or di(C.sub.1-6alkyl)aminocarbonyl, --CH(.dbd.NR.sup.11) or R.sup.7, wherein each of the aforementioned C.sub.1-6alkyl groups in the definition of R.sup.9a may optionally and each individually be substituted with one or two substituents each independently selected from hydroxy, C.sub.1-6alkyloxy, hydroxyC.sub.1-6alkyloxy, carboxyl, C.sub.1-6alkyloxycarbonyl, cyano, amino, imino, mono- or di(C.sub.1-4alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.pR.sup.6, --NH--S(.dbd.O).sub.pR.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6,--C(.dbd.NH)R.sup.6, R.sup.7; and wherein R.sup.9a may also be taken together with R.sup.10 to form a bivalent radical of formula (d-1), (d-2), (d-3), (d-4), (d-5) or (d-6) as defined for R.sup.9 and R.sup.10.

8. A compound according to claim 1 wherein R.sup.3 is C.sub.2-6alkenyl substituted with cyano.

9. A compound according to claim 1 wherein R.sup.3 is R.sup.7; C.sub.1-6alkyl substituted with cyano and R.sup.7; C.sub.2-6alkenyl substituted with cyano and R.sup.7; C.sub.1-6alkyl substituted with R.sup.7; --C(.dbd.N--O--R.sup.8)--C.sub.1-4alkyl; C.sub.1-6alkyl substituted with hydroxy and a second substituent selected from cyano or R.sup.7.

10. A compound according to claim 1 wherein R.sup.3 is R.sup.7, NR.sup.13R.sup.14, --C(.dbd.O)R.sup.15, --CH.dbd.N--NH--C(.dbd.O)R.sup.16, --C(.dbd.O)NHR.sup.13, --C(.dbd.O)NR.sup.13R.sup.14, --C(.dbd.N--OR.sup.8)--C.sub.1-4alkyl, C.sub.1-6alkyl substituted with cyano, C.sub.1-6alkyl substituted twice with cyano, C.sub.1-6alkyl substituted with NR.sup.9R.sup.10, C.sub.1-6alkyl substituted with hydroxy and cyano, C.sub.1-6alkyl substituted with hydroxy and R.sup.7, C.sub.1-6alkyloxy C.sub.1-6alkyl, C.sub.1-6alkyloxy C.sub.1-6alkyl substituted with cyano, C.sub.2-6alkenyl substituted with R.sup.7, C.sub.2-6alkenyl substituted with cyano, C.sub.2-6alkenyl substituted twice with cyano, C.sub.2-6alkenyl substituted with cyano and R.sup.7, C.sub.2-6alkenyl substituted with cyano and --C(.dbd.O)--C.sub.1-6alkyl, C.sub.2-6alkenyl substituted with cyano and halo, C.sub.2-6alkenyl substituted with --C(.dbd.O)--NR.sup.9R.sup.10, C.sub.2-6alkenyl substituted with halo, C.sub.2-6alkenyl substituted twice with halo or C.sub.2-6alkenyl substituted with NR.sup.9R.sup.10.

11. A compound according to claim 1 wherein R.sup.2' is cyano or aminocarbonyl.

12. A compound according to claim 1 wherein R.sup.2' is cyano.

13. A compound according to claim 1 wherein X.sub.3 is --C(.dbd.O)--, --CH.sub.2--C(.dbd.O)--, or --C(.dbd.N--OR.sup.8)--C.sub.1-4alkanediyl-.

14. A compound according to claim 1 wherein n' is 0.

15. A compound according to claim 1 wherein m is 2.

16. A compound according to claim 1 wherein R.sup.4 is C.sub.1-6alkyl; nitro; amino; halo; C.sub.1-6alkyloxy or R.sup.7.

17. A compound according to claim 1 wherein R.sup.4 is C.sub.1-6alkyl.

18. A compound according to claim 1 wherein R.sup.4 is methyl.

19. A compound according to claim 1 wherein X.sub.1 is NH or O.

20. A compound according to claim 1 wherein X.sub.1 is NH.

21. A compound according to claim 1 wherein R.sup.1 is hydrogen or C.sub.1-4alkyl.

22. A compound according to claim 1 wherein R.sup.1 is hydrogen.

23. A pharmaceutical composition according to claim 4 wherein the compound as claimed in claim 1 is in the form of nanoparticles which have a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than 1000 nm.

24. A composition according to claim 23 wherein the surface modifier is a non-ionic or anionic surfactant.

25. A solid dispersion comprising: (a) a compound according to claim 1; and (b) one or more pharmaceutically acceptable water-soluble polymers.

26. A solid dispersion according to claim 25 wherein the water-soluble polymer is a polymer that has an apparent viscosity of 1 to 5000 mPas when dissolved at 20 C. in an aqueous solution at 2% (w/v).

27. A solid dispersion according to claim 25 wherein the water-soluble polymer is a polymer that has an apparent viscosity of 1 to 700 mPas when dissolved at 20 C. in an aqueous solution at 2% (w/v).

28. A solid dispersion according to claim 25 wherein the water-soluble polymer is a polymer that has an apparent viscosity of 1 to 100 mPas when dissolved at 20 C. in an aqueous solution at 2% (w/v).

29. A solid dispersion according to claim 25 wherein the water-soluble polymer is selected from alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcelluloses, alkali metal salts of carboxyalkylcelluloses, carboxyalkylalkylcelluloses, carboxyalkylcellulose esters, starches, pectines, chitin derivates, di-, oligo- and polysaccharides, alginic acid or alkali metal and ammonium salts thereof, carrageenans, galactomannans, tragacanth, agar-agar, gummi arabicum, guar gummi and xanthan gummi, polyacrylic acids and the salts thereof, polymethacrylic acids and the salts thereof, methacrylate copolymers, polyvinylalcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate, combinations of polyvinylalcohol and polyvinylpyrrolidone, polyalkylene oxides, copolymers of ethylene oxide and propylene oxide, cyclodextrins.

30. A solid dispersion according to claim 25 wherein the water-soluble polymer is hydroxypropyl methylcellulose.

31. A solid dispersion according to claim 25 wherein the ratio of components (a):(b) varies between 1/100 to 100/1.

32. A solid dispersion according to claim 25 wherein the ratio of components (a):(b) varies between 1/10 to 10/1.

33. A solid dispersion according to claim 25 wherein the ratio of components (a):(b) varies between 1/5 to 5/1.

34. A solid dispersion according to claim 25 which is in the form of a solid solution comprising (a) and (b).

35. A particle consisting of a solid dispersion according to claim 25.

36. A particle according to claim 35 wherein the particle has a particle size of less than 600 .mu.m.

37. A particle according to claim 35 wherein the particle has a particle size of less than 400 .mu.m.

38. A particle according to claim 35 wherein the particle has a particle size of less than 125 .mu.m.

39. A process for preparing a solid dispersion according to claim 35 comprising the steps of dissolving the two components (a) and (b) in an appropriate solvent and spraying the resulting solution through the nozzle of a spray dryer followed by evaporating the solvent from the resulting droplets at elevated temperatures.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc