Claims
- 1. A compound of the formula:
- 2. A compound according to claim 1,
- 3. A compound according to claim 2 of the formula:
- 4. A compound according to claim 2 that is:
(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-ylamino)-acetic acid ethyl ester; (1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-(3,5-dimethoxy-benzyl)-amine; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-piperidin-1-yl-acetamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-phenyl-acetamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-fluoro-6-trifluoromethyl-benzamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-4-fluoro-3-trifluoromethyl-benzamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2,3,6-trifluoro-benzamide; or pharmaceutically acceptable salts thereof.
- 5. A pharmaceutical composition comprising a compound of the formula:
- 6. A pharmaceutical composition according to claim 5, wherein
R1 is H, alkyl (C1-C6), alkoxy, cycloalkyl, cycloalkylalkyl, alkanoyl, benzyl, or benzoyl; wherein each of the above is optionally substituted with up to 5 groups that are independently alkyl (C1-C6), halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —SH, —S-alkyl, —NO2, or —NR′R″, wherein R′ and R″ are independently H or alkyl (C1-C6); R2 is H, alkyl (C1-C6), cycloalkyl, cycloalkylalkyl, arylalkyl, halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)(C1-C6 alkyl), aminoalkyl, mono- or dialkylaminoalkyl, phenyl, or benzyl; wherein each of the above is optionally substituted with up to 5 groups that are independently alkyl (C1-C6), halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —SH, —S-alkyl, —NO2, or —NR′R″, wherein R′ and R″ are independently H or alkyl (C1-C6); or R2 is: 66wherein R4 represents H, alkyl (C1-C6), halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —SH, —S-alkyl, —NO2, —NH2, mono- or dialkylamino, aminoalkyl, mono- or dialkylaminoalkyl, pyrrolyl, piperidyl, piperazyl, phenyl, or benzyl; wherein each of the above is optionally substituted with up to 5 groups that are independently alkyl (C1-C6), halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —SH, —S-alkyl, —NO2, or —NR′R″, wherein R′ and R″ are independently H or alkyl (C1-C6); R3 is H, alkyl (C1-C15), cycloalkyl, cycloalkylalkyl, halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —CONH2, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)(C1-C6 alkyl), —CO2R8, —CF3, —OCF3, —NO2, —NH2, aminoalkyl, mono- or dialkylaminoalkyl, phenyl, or benzyl; wherein each of the above is optionally substituted with up to 5 groups that are independently alkyl (C1-C6), halogen, haloalkyl, —OH, alkoxy, hydroxyalkyl, —SH, —S-alkyl, —NO2, or —NR′R″, wherein R′ and R″ are H or alkyl (C1-C6); R7 is H, alkyl (C1-C6), alkoxy, or benzyl, wherein each is optionally substituted with up to three groups that are independently alkyl, alkoxy, —NO2, —OH, halogen, —CN, —CF3, or —OCF3; and R8 is H, alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; wherein each of the above is optionally substituted with up to 5 groups that are independently alkyl (C1-C6), alkoxy (C1-C6), halogen, haloalkyl, —CF3, —OCF3, —OH, alkoxy, hydroxyalkyl, —CN, —CO2H, —SH, —S-alkyl, —NO2, or —NR′R″, wherein R′ and R″ are independently H or alkyl (C1-C6).
- 7. A pharmaceutical composition according to claim 6 of the structure:
- 8. A pharmaceutical composition according to claim 6 comprising (1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-ylamino)-acetic acid ethyl ester; (1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-(3,5-dimethoxy-benzyl)-amine; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-piperidin-1-yl-acetamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-phenyl-acetamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2-fluoro-6-trifluoromethyl-benzamide; N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-4-fluoro-3-trifluoromethyl-benzamide; and N-(1-Benzyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-4-yl)-2,3,6-trifluoro-benzamide; or pharmaceutically acceptable salts thereof; with at least one pharmaceutically acceptable carrier or excipient.
- 9. The pharmaceutical composition of any of claims 5, 6, 7, or 8, further comprising at least one additional chemotherapeutic agent.
- 10. A method for inhibiting drug transport from target cells or tissues in an animal undergoing chemotherapy, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to inhibit drug transport.
- 11. The method of claim 8, wherein drug transport is mediated by P-glycoprotein.
- 12. A method for preventing drug resistance in target cells or tissues in an animal undergoing chemotherapy, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to attenuate drug resistance in the target cells or tissues of the animal.
- 13. A method for enhancing the therapeutic efficacy of an antiproliferative drug in target cells or tissues of an animal undergoing chemotherapy, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to enhance delivery of the antiproliferative drug to the target cells or tissues of the animal.
- 14. A method for enhancing the therapeutic efficacy of an anti-infective agent in an animal, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to inhibit drug transport from an infectious agent in the animal.
- 15. A method for enhancing the delivery of a therapeutic agent to target cells or tissues of an animal, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to enhance delivery of the therapeutic agent to the target cells or tissues of the animal.
- 16. The method of claim 15, wherein the target cells or tissues are brain, testes, eye, or leukocytes.
- 17. A method for enhancing the absorption of an orally-delivered therapeutic agent in target cells or tissues of an animal, comprising administering to the animal the pharmaceutical composition of any of claims 5, 6, 7, or 8, in an amount effective to enhance drug transport across the gastrointestinal tract.
Parent Case Info
[0001] This application is a divisional of U.S. patent application Ser. No. 09/822,743, filed Mar. 30, 2001, which claims priority from U.S. Provisional Application No. 60/193,109, filed Mar. 30, 2000 and U.S. Provisional Application No. 60/193,104, filed Mar. 30, 2000, the disclosure of each of which is explicitly incorporated by reference herein.
Government Interests
[0002] This invention was made with government support Grant CA64983 awarded by the United States Public Health Service. The government has certain rights in the invention.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60193109 |
Mar 2000 |
US |
|
60193104 |
Mar 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09822743 |
Mar 2001 |
US |
Child |
10174849 |
Jun 2002 |
US |