US4746659A
Expired / Lapsed
US
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Diastereomers of 10-alkyl-10-deazaminopterins and process for preparing the same
Assignee: SRI International Inc
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Filing: 1985-12-30
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Granted: 1988-05-24
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Expires: 2005-12-30
Abstract
Abstract Diastereomers of 10-alkyl-10-deazaminopterins are provided, as well as a synthesis for their preparation as the individual d,L. and l,L.-diastereomers, the d,L-10-ethyl diastereomer being three times as potent against L1210 cells as the l,L-10-ethyl diastereomer, and the l,L-10-ethyl diastereomer being approximately one-half as toxic as the d,L-10-ethyl diastereomer.
Inventors
- 👤 Joseph I. DeGraw
- 👤 Pamela H. Christie
- 👤 Francis M. Sirotnak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 08:26
CPC Classifications
C; C07; C07D; C07D475/00; C07D475/06; C07D475/08; A; A61; A61P; A61P29/00; A61P35/00; A61P35/02
Claims Analysis
Total Claims: 64
Claim 1
Independent Claim
57 words
The resolved d,L and l,L-diastereomers of 10-alkyl-10-deazaminopterin compounds having the formula: ##STR6## wherein: R 1 and R 2 are both selected from the group consisting of hydrogen and alkyl having from one to about eight carbon atoms, R 1 is different from R 2 , and at least one of R 1 and R 2 is alkyl.
Claim 2
Dependent Claim
57 words
The resolved d,L and l,L-diastereomers of 10-alkyl-10-deazaminopterin compounds having the formula: ##STR6## wherein: R 1 and R 2 are both selected from the group consisting of hydrogen and alkyl having from one to about eight carbon atoms, R 1 is different from R 2 , and at least one of R 1 and R 2 is alkyl.
Claim 3
Dependent Claim
28 words
The resolved d,L and l,L-diastereomers of 10-alkyl-10-deazaminopterin compounds according to claim 1 in which one of R 1 and R 2 is alkyl and the other is hydrogen.
Claim 4
Dependent Claim
18 words
The resolved d,L and l,L-diastereomers of 10-alkyl-10-deazaminopterin compounds according to claim 2 in which the alkyl is ethyl.
Claim 5
Dependent Claim
18 words
The resolved d,L and l,L-diastereomers of 10-alkyl-10-deazaminopterin compounds according to claim 2 in which the alkyl is methyl.
Claim 6
Dependent Claim
18 words
10-Deazaminopterin compounds according to claim 1 in which both of R 1 and R 2 are different alkyl.
Claim 7
Dependent Claim
1 words
d,L-10-ethyl-10-deazaminopterin.
Claim 8
Dependent Claim
1 words
d,L-10-ethyl-10-deazaminopterin.
Claim 9
Dependent Claim
1 words
l,L-10-ethyl-10-deazaminopterin.
Claim 10
Dependent Claim
1 words
l,L-10-ethyl-10-deazaminopterin.
Claim 11
Dependent Claim
51 words
A pharmaceutical composition in dosage unit form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per dosage unit therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 12
Dependent Claim
51 words
A pharmaceutical composition in dosage unit form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per dosage unit therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 13
Dependent Claim
22 words
A pharmaceutical composition according to claim 8 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 14
Dependent Claim
49 words
A pharmaceutical composition in tablet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per tablet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 15
Dependent Claim
49 words
A pharmaceutical composition in tablet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per tablet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 16
Dependent Claim
22 words
A pharmaceutical composition according to claim 10 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 17
Dependent Claim
49 words
A pharmaceutical composition in capsule form for treating leukemia or an ascites tumor comprising an amount within the range from 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per capsule therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 18
Dependent Claim
49 words
A pharmaceutical composition in capsule form for treating leukemia or an ascites tumor comprising an amount within the range from 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per capsule therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 19
Dependent Claim
22 words
A pharmaceutical composition according to claim 12 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 20
Dependent Claim
50 words
A pharmaceutical composition in suppository form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per suppository therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 21
Dependent Claim
50 words
A pharmaceutical composition in suppository form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per suppository therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 22
Dependent Claim
22 words
A pharmaceutical composition according to claim 14 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 23
Dependent Claim
50 words
A pharmaceutical composition in cachet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per cachet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 24
Dependent Claim
50 words
A pharmaceutical composition in cachet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin per cachet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 25
Dependent Claim
22 words
A pharmaceutical composition according to claim 16 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 26
Dependent Claim
51 words
A pharmaceutical composition in sterile aqueous form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic sterile inert aqueous carrier or diluent therefor.
Claim 27
Dependent Claim
51 words
A pharmaceutical composition in sterile aqueous form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of d,L-10-ethyl-10-deazaminopterin therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic sterile inert aqueous carrier or diluent therefor.
Claim 28
Dependent Claim
22 words
A pharmaceutical composition according to claim 18 in which the d,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 29
Dependent Claim
11 words
A pharmaceutical composition according to claim 18 in aqueous solution form.
Claim 30
Dependent Claim
11 words
A pharmaceutical composition according to claim 18 in aqueous dispersion form.
Claim 31
Dependent Claim
51 words
A pharmaceutical composition in dosage unit form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per dosage unit therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 32
Dependent Claim
51 words
A pharmaceutical composition in dosage unit form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per dosage unit therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 33
Dependent Claim
22 words
A pharmaceutical composition according to claim 22 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 34
Dependent Claim
49 words
A pharmaceutical composition in tablet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per tablet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 35
Dependent Claim
49 words
A pharmaceutical composition in tablet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per tablet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic carrier or diluent therefor.
Claim 36
Dependent Claim
22 words
A pharmaceutical composition according to claim 24 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 37
Dependent Claim
48 words
A pharmaceutical composition in capsule form for treating leukemia or an ascites tumor comprising an amount within the range from 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per capsule therapeutically effective to ameliorate leukemia or the ascites, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 38
Dependent Claim
48 words
A pharmaceutical composition in capsule form for treating leukemia or an ascites tumor comprising an amount within the range from 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per capsule therapeutically effective to ameliorate leukemia or the ascites, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 39
Dependent Claim
22 words
A pharmaceutical composition according to claim 26 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 40
Dependent Claim
50 words
A pharmaceutical composition in suppository form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per suppository therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 41
Dependent Claim
50 words
A pharmaceutical composition in suppository form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per suppository therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 42
Dependent Claim
22 words
A pharmaceutical composition according to claim 28 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 43
Dependent Claim
50 words
A pharmaceutical composition in cachet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per cachet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 44
Dependent Claim
50 words
A pharmaceutical composition in cachet form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin per cachet therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic inert carrier or diluent therefor.
Claim 45
Dependent Claim
22 words
A pharmaceutical composition according to claim 30 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 46
Dependent Claim
51 words
A pharmaceutical composition in sterile aqueous form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic sterile inert aqueous carrier or diluent therefor.
Claim 47
Dependent Claim
51 words
A pharmaceutical composition in sterile aqueous form for treating leukemia or an ascites tumor comprising an amount within the range from about 0.1 to about 500 mg of l,L-10-ethyl-10-deazaminopterin therapeutically effective to ameliorate leukemia or the ascites tumor, together with a pharmaceutically acceptable nontoxic sterile inert aqueous carrier or diluent therefor.
Claim 48
Dependent Claim
22 words
A pharmaceutical composition according to claim 32 in which the l,L-10-ethyl-10-deazaminopterin is in the form of a pharmaceutically acceptable acid addition salt.
Claim 49
Dependent Claim
11 words
A pharmaceutical composition according to claim 32 in aqueous solution form.
Claim 50
Dependent Claim
11 words
A pharmaceutical composition according to claim 32 in aqueous dispersion form.
Claim 51
Dependent Claim
41 words
A process for treating leukemia and ascites tumors which comprises administering to a warm-blooded animal having an abnormal proportion of leukocytes or other evidence of the malignancy, a therapeutic and relatively nontoxic amount of d,L-10-ethyl-10-deazaminopterin, to ameliorate leukemia or ascites tumors.
Claim 52
Dependent Claim
41 words
A process for treating leukemia and ascites tumors which comprises administering to a warm-blooded animal having an abnormal proportion of leukocytes or other evidence of the malignancy, a therapeutic and relatively nontoxic amount of d,L-10-ethyl-10-deazaminopterin, to ameliorate leukemia or ascites tumors.
Claim 53
Dependent Claim
18 words
A process according to claim 36 in which the d,L-10-ethyl-10-deazaminopterin is administered as a pharmaceutically acceptable salt thereof.
Claim 54
Dependent Claim
27 words
A process according to claim 36 in which the d,L-10-ethyl-10-deazaminopterin is administered in an amount within the range from about 0.1 to about 500 mg per day.
Claim 55
Dependent Claim
18 words
A process according to claim 36 in which the d,L-10-ethyl-10-deazaminopterin is administered with an inert diluent or carrier.
Claim 56
Dependent Claim
13 words
A process according to claim 36 in which the d,L-10-ethyl-10-deazaminopterin is administered orally.
Claim 57
Dependent Claim
13 words
A process according to claim 36 in which the d,L-10-ethyl-10-deazaminopterin is administered parenterally.
Claim 58
Dependent Claim
41 words
A process for treating leukemia and ascites tumors which comprises administering to a warm-blooded animal having an abnormal proportion of leukocytes or other evidence of the malignancy, a therapeutic and relatively nontoxic amount of l,L-10-ethyl-10-deazaminopterin, to ameliorate leukemia or ascites tumors.
Claim 59
Dependent Claim
41 words
A process for treating leukemia and ascites tumors which comprises administering to a warm-blooded animal having an abnormal proportion of leukocytes or other evidence of the malignancy, a therapeutic and relatively nontoxic amount of l,L-10-ethyl-10-deazaminopterin, to ameliorate leukemia or ascites tumors.
Claim 60
Dependent Claim
18 words
A process according to claim 42 in which the l,L-10-ethyl-10-deazaminopterin is administered as a pharmaceutically acceptable salt thereof.
Claim 61
Dependent Claim
27 words
A process according to claim 42 in which the l,L-10-ethyl-10-deazaminopterin is administered in an amount within the range from about 0.1 to about 500 mg per day.
Claim 62
Dependent Claim
18 words
A process according to claim 42 in which the l,L-10-ethyl-10-deazaminopterin is administered with an inert diluent or carrier.
Claim 63
Dependent Claim
13 words
A process according to claim 42 in which the l,L-10-ethyl-10-deazaminopterin is administered orally.
Claim 64
Dependent Claim
13 words
A process according to claim 42 in which the l,L-10-ethyl-10-deazaminopterin is administered parenterally.
References Cited (Backward Citations)
US4393064A
Cited
US4369319A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-05-24 | 1991-11-23 | 1992-05-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-24 | 1995-11-23 | 1996-05-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-24 | 1999-11-23 | 2000-05-24 | $7700.00 | Window Closed / Lapsed |