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US4960790A
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Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
Assignee: University of Kansas
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Filing: 1989-03-09
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Granted: 1990-10-02
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Expires: 2009-03-09
Abstract
Abstract Derivatives of taxol represented by the formula <IMAGE> (II) wherein R and R' are each H or the residue of an amino acid selected from the group consisting of alanine, leucine, isoleucine, saline, phenylalanine, proline, lysine and arginine or a group of the formula <IMAGE> (III) wherein n is an integer of 1 to 3 and R2 and R3 are each hydrogen on an alkyl radical having from one to three carbon atoms or wherein R2 and R3 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring having four to five carbon atoms, with the proviso that at least one of R and R1 is not hydrogen, are provided together with pharmaceutical compositions of such derivatives. The taxol derivatives have increased water solubility as compared to taxol, and have excellent antitumor activity.
Inventors
- 👤 Valentino J. Stella
- 👤 Abraham E. Mathew
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 19:09
CPC Classifications
C; C07; C07D; C07D305/00; C07D305/14; A; A61; A61P; A61P35/00
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
131 words
A compound of the formula ##STR19## wherein R and R' are each H or the residue of an amino acid selected from the group consisting of alanine, leucine, isoleucine, valine, phenylalanine, proline, lysine and arginine or a group of the formula ##STR20## wherein n is an integer of 1 to 3 and R 2 and R 3 are each hydrogen or an alkyl radical having from one to three carbon atoms or wherein R 2 and R 3 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring having four or five carbon atoms or an acid addition salt thereof, with the proviso that at least one of R and R 1 is not hydrogen, and with the second proviso that said compound is not 2'-(β-alanyl)taxol.
Claim 2
Dependent Claim
131 words
A compound of the formula ##STR19## wherein R and R' are each H or the residue of an amino acid selected from the group consisting of alanine, leucine, isoleucine, valine, phenylalanine, proline, lysine and arginine or a group of the formula ##STR20## wherein n is an integer of 1 to 3 and R 2 and R 3 are each hydrogen or an alkyl radical having from one to three carbon atoms or wherein R 2 and R 3 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring having four or five carbon atoms or an acid addition salt thereof, with the proviso that at least one of R and R 1 is not hydrogen, and with the second proviso that said compound is not 2'-(β-alanyl)taxol.
Claim 3
Dependent Claim
32 words
A compound according to claim 1, wherein at least one of R and R' is a member selected from the group consisting of L-alanine, L-leucine, L-isoleucine, L-valine, L-phenylalanine, L-proline, L-lysine, and L-arginine.
Claim 4
Dependent Claim
49 words
A compound according to claim 1, wherein at least one of R and R' is a group of the formula ##STR21## wherein n is an integer of from 1 to 3 and R 2 and R 3 are each an alkyl radical having from one to three carbon atoms.
Claim 5
Dependent Claim
15 words
A compound according to claim 1, which is 2'-(N,N-dimethylglycyl)taxol or an acid addition salt thereof.
Claim 6
Dependent Claim
15 words
A compound according to claim 1, which is 2'-(N,N-diethylaminopropionyl)taxol or an acid addition salt thereof.
Claim 7
Dependent Claim
15 words
A compound according to claim 1, which is 7-(N,N-dimethylgylcyl)taxol, or an acid addition salt thereof.
Claim 8
Dependent Claim
15 words
A compound according to claim 1, which is 2',7-di(N,N-dimethylglycyl)taxol, or an acid addition salt thereof.
Claim 9
Dependent Claim
15 words
A compound according to claim 1, which is 7-(alanyl)taxol or an acid addition salt thereof.
Claim 10
Dependent Claim
139 words
A pharmaceutical composition comprising an effective antitumor amount of at least one compound of the formula ##STR22## wherein R and R' are each H or the residue of an amino acid selected from the group consisting of alanine, leucine, isoleucine, valine, phenylalanine, proline, lysine and arginine or a group of the formula ##STR23## wherein n is an integer of 1 to 3 and R 2 and R 3 are each hydrogen or an alkyl radical having from one to three carbon atoms or wherein R 2 and R 3 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring having four to five carbon atoms, with the proviso that at least one of R and R 1 is not hydrogen, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
Claim 11
Dependent Claim
139 words
A pharmaceutical composition comprising an effective antitumor amount of at least one compound of the formula ##STR22## wherein R and R' are each H or the residue of an amino acid selected from the group consisting of alanine, leucine, isoleucine, valine, phenylalanine, proline, lysine and arginine or a group of the formula ##STR23## wherein n is an integer of 1 to 3 and R 2 and R 3 are each hydrogen or an alkyl radical having from one to three carbon atoms or wherein R 2 and R 3 together with the nitrogen atom to which they are attached form a saturated heterocyclic ring having four to five carbon atoms, with the proviso that at least one of R and R 1 is not hydrogen, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.
Claim 12
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 2'-(N,N-dimethylglycyl)taxol.
Claim 13
Dependent Claim
15 words
A pharmaceutical composition according to claim 10, wherein said at least one compound is 2'-(N,N-diethylaminopropionyl)taxol.
Claim 14
Dependent Claim
24 words
A method for treating tumors which comprises administering to a patient an effective antitumor amount of at least one compound according to claim 1.
Claim 15
Dependent Claim
28 words
A method according to claim 12, wherein said treatment comprises treating tumors selected from the group consisting of human lung tumors, melanoma, leukemia, mammary tumors and colon cancer.
Claim 16
Dependent Claim
15 words
A compound according to claim 1, which is 7-(N,N-dimethylaminopropionyl)taxol or an acid addition salt thereof.
Claim 17
Dependent Claim
15 words
A compound according to claim 1, which is 2'-(L-alanyl)taxol or an acid addition salt thereof.
Claim 18
Dependent Claim
15 words
A compound according to claim 1, which is 2'-(L-lysyl)taxol or an acid addition salt thereof.
Claim 19
Dependent Claim
15 words
A compound according to claim 1, which is 7-(L-lysyl)taxol or an acid addition salt thereof.
Claim 20
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 7-(N,N-dimethylglycyl)-taxol.
Claim 21
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 2'7-di-(N,N-diethylaminopropionyl)taxol.
Claim 22
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 7-(N,N-diethylaminopropionyl)taxol.
Claim 23
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 2'-(L-alanyl)taxol.
Claim 24
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 7-(L-alanyl)taxol.
Claim 25
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 2'-(L-lysyl)taxol.
Claim 26
Dependent Claim
15 words
A pharmaceutical composition according to claim 9, wherein said at least one compound is 7-(L-lysyl)taxol.
Claim 27
Dependent Claim
21 words
A taxol derivative selected from the group consisting of 2'-(N,N-diethylaminopropionyl)taxol; 2'-(N,N-dimethylglycyl)taxol; 7-(N,N-dimethylglycyl)taxol; 2',7-di-(N,N-dimethylglycyl)taxol; 7-(N,N-diethylaminopropionyl)taxol; 2'-(L-lysyl)taxol; 7-(L-lysyl)taxol; and acid addition salts thereof.
Claim 28
Dependent Claim
21 words
A taxol derivative selected from the group consisting of 2'-(N,N-diethylaminopropionyl)taxol; 2'-(N,N-dimethylglycyl)taxol; 7-(N,N-dimethylglycyl)taxol; 2',7-di-(N,N-dimethylglycyl)taxol; 7-(N,N-diethylaminopropionyl)taxol; 2'-(L-lysyl)taxol; 7-(L-lysyl)taxol; and acid addition salts thereof.
Claim 29
Dependent Claim
16 words
A compound according to claim 25, wherein the acid addition salt is a methanesulphonic acid salt.
Claim 30
Dependent Claim
15 words
A compound according to claim 25, wherein the acid addition salt is an HCl salt.
Claim 31
Dependent Claim
11 words
A compound according to claim 25, which 2'-(N,N-diethylaminopropionyl)taxol methanesulphonic acid salt.
Claim 32
Dependent Claim
11 words
A compound according to claim 25, which is 2'-(N,N-diethylaminopropionyl)taxol HCl salt.
Claim 33
Dependent Claim
22 words
A pharmaceutical composition comprising an effective antitumor amount of at least one compound according to claim 25, and a pharmaceutically acceptable carrier.
Claim 34
Dependent Claim
19 words
A pharmaceutical composition according to claim 30, wherein said compound is 2'-(N,N-diethylaminopropionyl)taxol methanesulphonic acid salt or 2'-(N,N-diethylaminopropionyl)taxol HCl salt.
Claim 35
Dependent Claim
24 words
A method for treating tumors which comprises administering to a patient an effective antitumor amount of at least one compound according to claim 25.
Claim 36
Dependent Claim
24 words
A method for treating tumors which comprises administering to a patient an effective antitumor amount of at least one compound according to claim 28.
Claim 37
Dependent Claim
24 words
A method for treating tumors which comprises administering to a patient an effective antitumor amount of at least one compound according to claim 29.
References Cited (Backward Citations)
US4163058A
Cited
US4650803A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-10-01 | 1994-04-02 | 1994-10-02 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-10-01 | 1998-04-02 | 1998-10-02 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-10-01 | 2002-04-02 | 2002-10-02 | $7700.00 | Window Closed / Lapsed |