US4058602A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Synthesis, structure, and antitumor activity of 5,6-dihydro-5-azacytidine
Assignee: United States Department of Health and Human Services
•
Filing: 1976-08-09
•
Granted: 1977-11-15
•
Expires: 1996-08-09
Abstract
Abstract The compound 5,6-dihydro-5-azacytidine, 5AC[H], and non-toxic acid addition salts such as the hydrochloride, together with its preparation from 5-azacytidine (5-AC) by reduction of the 5,6-double bond of 5-AC with an alkali metal borohydride such as sodium borohydride. Additionally, 5,6-dihydro-5-azacytidine, 5AC[H], has antitumor activity for murine leukemia systems L1210 and P388 as an injectable. In comparison with the parent compound, 5-AC, the antitumor activity is comparable and 5AC[H] exhibits a more favorable therapeutic index. It also has better solution stability over a broad pH range. A structure for the HCl salt is given below. <IMAGE>
Inventors
- 👤 John A. Beisler
- 👤 Mohamed M. Abbasi
- 👤 John S. Driscoll
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 17:26
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/12
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
44 words
5,6dihydro-5 -azacytidine and a non-toxic acid addition salt thereof wherein such salt is selected from a group consisting of non-toxic mineral acid salts and salts of organic acids selected from one member of a group consisting of maleate, tartrate, citrate, acetate, benzoate, and borate.
Claim 2
Dependent Claim
44 words
5,6dihydro-5 -azacytidine and a non-toxic acid addition salt thereof wherein such salt is selected from a group consisting of non-toxic mineral acid salts and salts of organic acids selected from one member of a group consisting of maleate, tartrate, citrate, acetate, benzoate, and borate.
Claim 3
Dependent Claim
39 words
A process of reducing 5-azacytidine utilizing an alkali metal borohydride in hexamethylphosphoramide solution to produce the compound 5,6-dihydro-5-azacytidine as a boron complex and subsequently hydrolyzing said boron complex with a mineral acid to produce 5,6-dihydro-5-azacytidine as the acid salt.
Claim 4
Dependent Claim
39 words
A process of reducing 5-azacytidine utilizing an alkali metal borohydride in hexamethylphosphoramide solution to produce the compound 5,6-dihydro-5-azacytidine as a boron complex and subsequently hydrolyzing said boron complex with a mineral acid to produce 5,6-dihydro-5-azacytidine as the acid salt.
Claim 5
Dependent Claim
11 words
The process of claim 2 wherein the acid is hydrochloric acid.
Claim 6
Independent Claim
80 words
A method of inhibiting leukemia L1210 and P388 in mice which comprises utilizing an effective amount of 5,6-dihydro-5-azacytidine as an injectable in a dosage regimen of 6 mg/kg - 600 mg/kg of body weight of the compound 5,6-dihydro-5-azacytidine and a non-toxic acid addition salt thereof wherein such salt is selected from a group consisting of non-toxic mineral acid salts and salts of organic acids selected from one member of a group consisting of maleate, tartrate, citrate, acetate, benzoate, and borate.
Claim 7
Independent Claim
80 words
A method of inhibiting leukemia L1210 and P388 in mice which comprises utilizing an effective amount of 5,6-dihydro-5-azacytidine as an injectable in a dosage regimen of 6 mg/kg - 600 mg/kg of body weight of the compound 5,6-dihydro-5-azacytidine and a non-toxic acid addition salt thereof wherein such salt is selected from a group consisting of non-toxic mineral acid salts and salts of organic acids selected from one member of a group consisting of maleate, tartrate, citrate, acetate, benzoate, and borate.
Claim 8
Dependent Claim
10 words
The method of claim 4 wherein leukemia L1210 is inhibited.
Claim 9
Dependent Claim
10 words
The method of claim 4 wherein leukemia P388 is inhibited.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-11-14 | 1981-05-16 | 1981-11-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-11-14 | 1985-05-16 | 1985-11-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-11-14 | 1989-05-16 | 1989-11-15 | $7700.00 | Window Closed / Lapsed |