Patent US4439426A successfully refreshed from Google Patents.
US4439426A
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US
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Semisynthetic macrolidic antibiotics, intermediate compounds for their preparation and related pharmaceutical compositions containing them
Assignee: Pfizer Italia SRL
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Filing: 1982-01-08
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Granted: 1984-03-27
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Expires: 2002-01-08
Abstract
Abstract From the fermentation carried, out with mutants blocked in the synthesis respectively of erythromycin and of oleandomycin, namely Streptomyces erythreus ATCC 31772 and Streptomyces antibioticus ATCC 31771, using as the substrate a derivative of erythronolide A, namely (8S)-8-fluoroerythronolide A, a derivative of erythronolide B, namely (8S)-8-fluoroerythronolide B, or a derivative of 3-O-mycarosyl-erythronolide B, namely 3-O-mycarosyl-(8S)-fluoroerythronolide B, the corresponding (8S)-8-fluoro derivatives of the erythromycins A, B, C and D, as well as 3-O-oleandrosyl-5-desosaminyl-(8S)-8-fluoroerythronolide A and 3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-fluoroerythronolide B, all belonging to the class of the macrolide antibiotics are obtained. The preparation of the aforesaid substrate comprises the convention of erythronolide A, erythronolide B or 3-O-mycarosyl-erythronolide B into the corresponding hermiacetal, the reaction of the latter with a compound capable of generating electrophlic fluorine and the opening of the resulting acetal with aqueous acid.
Inventors
- 👤 Luciano Toscano
- 👤 Leonardo M. Cappelletti
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 13:30
CPC Classifications
C; C07; C07D; C07D493/00; C07D493/02; C07D493/08; C07D313/00; C07H; C07H17/00; C07H17/04; C07H17/08; C12; C12N; C12N1/00; C12N1/20; C12N1/205; C12P; C12P19/00; C12P19/44; C12P19/60; C12P19/62; C12R; C12R2001/00; C12R2001/01; C12R2001/465; C12R2001/48; Y; Y10; Y10S; Y10S435/00; Y10S435/8215; Y10S435/822; Y10S435/886; Y10S435/888
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
6 words
(8S)-8-fluoroerythronolide A, having the formula: ##STR7##
Claim 2
Dependent Claim
6 words
(8S)-8-fluoroerythronolide A, having the formula: ##STR7##
Claim 3
Dependent Claim
6 words
(8S)-8-fluoroerythronolide A-6,9;9,11-acetal, having the formula: ##STR8##
Claim 4
Dependent Claim
6 words
(8S)-8-fluoroerythronolide A-6,9;9,11-acetal, having the formula: ##STR8##
Claim 5
Dependent Claim
7 words
8,9-anhydroerythronolide A 6,9-hemiacetal, having the formula: ##STR9##
Claim 6
Dependent Claim
7 words
8,9-anhydroerythronolide A 6,9-hemiacetal, having the formula: ##STR9##
Claim 7
Dependent Claim
6 words
(8S)-8-fluoroerythronolide B, having the formula: ##STR10##
Claim 8
Dependent Claim
6 words
(8S)-8-fluoroerythronolide B, having the formula: ##STR10##
Claim 9
Dependent Claim
6 words
(8S)-8-fluoroerythronolide B-6,9;9,11-acetal, having the formula: ##STR11##
Claim 10
Dependent Claim
6 words
(8S)-8-fluoroerythronolide B-6,9;9,11-acetal, having the formula: ##STR11##
Claim 11
Dependent Claim
6 words
3-O-mycarosyl-(8S)-8-fluoroerythronolide B, having the formula: ##STR12##
Claim 12
Dependent Claim
6 words
3-O-mycarosyl-(8S)-8-fluoroerythronolide B, having the formula: ##STR12##
Claim 13
Dependent Claim
6 words
3-O-mycarosyl-(8S)-8-fluoroerythrnolide B-6,9;9,11-acetal having the formula: ##STR13##
Claim 14
Dependent Claim
6 words
3-O-mycarosyl-(8S)-8-fluoroerythrnolide B-6,9;9,11-acetal having the formula: ##STR13##
Claim 15
Dependent Claim
6 words
3-O-mycarosyl-8,9-anhydroerythronolide B-6,9-hemiacetal having the formula: ##STR14##
Claim 16
Dependent Claim
6 words
3-O-mycarosyl-8,9-anhydroerythronolide B-6,9-hemiacetal having the formula: ##STR14##
Claim 17
Dependent Claim
12 words
(8S)-8-fluoroerythromycin A, having the formula ##STR15## or the pharmaceutically acceptable salts thereof.
Claim 18
Dependent Claim
12 words
(8S)-8-fluoroerythromycin A, having the formula ##STR15## or the pharmaceutically acceptable salts thereof.
Claim 19
Dependent Claim
12 words
(8S)-8-fluoroerythromycin B, having the formula ##STR16## or the pharmaceutically acceptable salts thereof.
Claim 20
Dependent Claim
12 words
(8S)-8-fluoroerythromycin B, having the formula ##STR16## or the pharmaceutically acceptable salts thereof.
Claim 21
Dependent Claim
12 words
(8S)-8-fluoroerythromycin C, having the formula ##STR17## or the pharmaceutically acceptable salts thereof.
Claim 22
Dependent Claim
12 words
(8S)-8-fluoroerythromycin C, having the formula ##STR17## or the pharmaceutically acceptable salts thereof.
Claim 23
Dependent Claim
12 words
(8S)-8-fluoroerythromycin D, having the formula ##STR18## or the pharmaceutically acceptable salts thereof.
Claim 24
Dependent Claim
12 words
(8S)-8-fluoroerythromycin D, having the formula ##STR18## or the pharmaceutically acceptable salts thereof.
Claim 25
Dependent Claim
12 words
3-O-oleandrosyl-5-O-desosaminyl-(8s)-8-fluoroerythronolide A, having the formula ##STR19## or the pharmaceutically acceptable salts thereof.
Claim 26
Dependent Claim
12 words
3-O-oleandrosyl-5-O-desosaminyl-(8s)-8-fluoroerythronolide A, having the formula ##STR19## or the pharmaceutically acceptable salts thereof.
Claim 27
Dependent Claim
12 words
3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-fluoroerythronolide B, having the formula ##STR20## or the pharmaceutically acceptable salts thereof.
Claim 28
Dependent Claim
12 words
3-O-oleandrosyl-5-O-desosaminyl-(8S)-8-fluoroerythronolide B, having the formula ##STR20## or the pharmaceutically acceptable salts thereof.
Claim 29
Dependent Claim
15 words
Compounds according to claim 9, 11 or 13 in the form of the carbonate salt.
Claim 30
Dependent Claim
27 words
Pharmaceutical composition containing an antibiotic-effective amount of a compound of any one of claims 9, 10, 11, 12, 13 or 14 with a pharmaceutically acceptable excipient therefor.
Claim 31
Dependent Claim
15 words
Composition of claim 16, wherein said composition is in a form suitable for oral administration.
Claim 32
Dependent Claim
17 words
Composition according to claim 16, wherein said amount is between 10 and 1000 mg of said compound.
Claim 33
Dependent Claim
20 words
A pharmaceutically acceptable ester or salt-ester of the compound as claimed in claim 9, 10, 11, 12, 13 or 14.
Claim 34
Dependent Claim
42 words
A compound as claimed in claim 19 selected from the group consisting of (8S)-8-fluoroerythromycin A acetate, (8S)-8-fluoroerythromycin A propionate, (8S)-8-fluoroerythromycin A butyrate, (8S)-8-fluoroerythromycin ether succinate, (8S)-8-fluoroerythromycin A succinate, (8S)-8-fluoroerythromycin A lactobionate, (8S)-8-fluoroerythromycin A stearate, (8S)-8-fluoroerythromycin A propionate laurylsulphate, and (8S)-8-fluoroerythromycin A carbonate.
Claim 35
Dependent Claim
43 words
A compound as claimed in claim 19 selected from the group consisting of (8S)-8-fluoroerythromycin B acetate, (8S)-8-fluoroerythromycin B propionate, (8S)-8-fluoroerythromycin B butyrate, (8S)-8-fluoroerythromycin B ethyl succinate, (8S)-8-fluoroerythromycin B succinate, (8S)-8-fluoroerythromycin B lactobionate, (8S)-8-fluoroerythromycin B stearate, (8S)-8-fluoroerythromycin B propionate laurylsulphate, and (8S)-8-fluoroerythromycin B carbonate.
Claim 36
Dependent Claim
42 words
A compound as claimed in claim 19 selected from the group of (8S)-8-fluoroerythromycin C acetate, (8S)-8-fluoroerythromycin C propionate, (8S)-8-fluoroerythromycin C butyrate, (8S)-8-fluoroerythromycin C ethyl succinate, (8S)-8-fluoroerythromycin C succinate, (8S)-8-fluoroerythromycin C lactobionate, (8S)-8-fluoroerythromycin C stearate, (8S)-8-fluoroerythromycin C propionate laurylsulphate, and (8S)-8-fluoroerythromycin C carbonate.
Claim 37
Dependent Claim
43 words
A compound as claimed in claim 19 selected from the group consisting of (8S)-8-fluoroerythromycin D acetate, (8S)-8-fluoroerythromycin D propionate, (8S)-8-fluoroerythromycin D butyrate, (8S)-8-fluoroerythromycin D ethyl succinate, (8S)-8-fluoroerythromycin D succinate, (8S)-8-fluoroerythromycin D lactobionate, (8S)-8-fluoroerythromycin D stearate, (8S)-8-fluoroerythromycin D propionate laurylsulphate, and (8S)-8-fluoroerythromycin D carbonate.
Claim 38
Dependent Claim
40 words
A compound as claimed in claim 19 selected from the group consisting of 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A propionate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A butyrate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A ethyl succinate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A succinate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A lactobionate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A stearate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A propionate laurylsulphate, and 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide A carbonate.
Claim 39
Dependent Claim
43 words
A compound as claimed in claim 19 selected from the group consisting of 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B acetate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B propionate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B butyrate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B ethyl succinate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-3-fluoroerythronolide B succinate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B lactobionate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B stearate, 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B propionate laurylsulphate, and 3-O-oleandrosyl-5-O-desoaminyl-(8S)-8-fluoroerythronolide B carbonate.
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) | 1987-03-27 | 1987-09-26 | 1988-03-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-03-27 | 1991-09-26 | 1992-03-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-03-27 | 1995-09-26 | 1996-03-27 | $7700.00 | Window Closed / Lapsed |