US4100276A
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Fusidic acid derivatives
Assignee: Leo Pharma AS
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Filing: 1976-11-24
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Granted: 1978-07-11
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Expires: 1996-11-24
Abstract
Abstract The invention relates to a new series of fusidic acid derivatives, to salts and easily hydrolyzable esters thereof, to the preparation of these compounds and to pharmaceutical compositions containing the compounds, the new compounds having the general formula: <IMAGE> I in which Q1 and Q2 stand for the group <IMAGE> or oxygen, A represents oxygen or sulphur, and R1 stands for a straight or branched alkyl radical having from 1 to 12 carbon atoms, R1 can further be an alkenyl or alkynyl radical having from 3 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an aralkyl or aryl radical, R1 can also be a heterocyclic radical having 5 or 6 ring atoms and containing oxygen, sulphur and/or nitrogen atoms, R1 optionally being further substituted, and in which formula I the dotted line between C-24 and C-25 indicates that the carbon atoms in question are connected by either a double bond or a single bond, and the asterix at C-20 indicates that the compounds exist in two diastereomeric forms, and thus the invention comprises the pure diastereomers as well as mixtures of these.
Inventors
- 👤 Welf von Daehne
- 👤 Poul Rodbroe Rasmussen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 12:28
CPC Classifications
C; C07; C07J; C07J51/00; A; A61; A61P; A61P31/00; A61P31/04; C07J13/00; C07J31/00; C07J31/003; C07J41/00; C07J41/0033; C07J41/0088
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
175 words
A compound of the formula I: ##STR17## in which formula the dotted line between C-24 and C-25 indicates that the carbon atoms in question are connected by either a double bond or a single bond, and the asterix at C-20 indicates that the compounds exist in two diastereomeric forms; and in which formula Q 1 and Q 2 stand for the group ##STR18## or oxygen, A represents oxygen or sulphur, and R 1 stands for a straight or branched, unsubstituted or substituted alkyl radical having from 1 to 12 carbon atoms, an alkenyl radical having from 3 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an unsubstituted or halo- or lower alkyl-substituted phenyl-lower alkyl or phenyl radical; a naphthyl radical; or a heterocyclic radical having 5 or 6 ring atoms and containing one oxygen, sulphur or nitrogen atom; the pure diastereomers of the compounds of formula I and mixtures thereof, and pharmaceutically acceptable non-toxic salts and easily hydrolysable esters of the compounds of formula I.
Claim 2
Dependent Claim
175 words
A compound of the formula I: ##STR17## in which formula the dotted line between C-24 and C-25 indicates that the carbon atoms in question are connected by either a double bond or a single bond, and the asterix at C-20 indicates that the compounds exist in two diastereomeric forms; and in which formula Q 1 and Q 2 stand for the group ##STR18## or oxygen, A represents oxygen or sulphur, and R 1 stands for a straight or branched, unsubstituted or substituted alkyl radical having from 1 to 12 carbon atoms, an alkenyl radical having from 3 to 6 carbon atoms, a cycloalkyl radical having from 3 to 7 carbon atoms in the alicyclic ring, an unsubstituted or halo- or lower alkyl-substituted phenyl-lower alkyl or phenyl radical; a naphthyl radical; or a heterocyclic radical having 5 or 6 ring atoms and containing one oxygen, sulphur or nitrogen atom; the pure diastereomers of the compounds of formula I and mixtures thereof, and pharmaceutically acceptable non-toxic salts and easily hydrolysable esters of the compounds of formula I.
Claim 3
Dependent Claim
118 words
A compound of the formula I of claim 1 in which Q 1 and Q 2 stand for the group ##STR19## or oxygen, A represents oxygen or sulphur, and R 1 stands for a straight or branched, unsubstituted or with hydroxy, amino or halogen substituted alkyl radical having from 1 to 12 carbon atoms, an alkenyl radical having from 3 to 4 carbon atoms, a cyclohexyl radical, an unsubstituted or with halogen or lower alkyl substituted phenyl radical, a phenyl-lower alkyl radical, a naphthyl radical, or a furfuryl or pyridyl radical; the pure diastereomers of the compounds of formula I and mixtures thereof, and pharmaceutically acceptable non-toxic salts or easily hydrolysable esters of the compounds of formula I.
Claim 4
Dependent Claim
15 words
A compound of the formula I of claim 1 in which A stands for oxygen.
Claim 5
Dependent Claim
15 words
A compound of the formula I of claim 1 in which A stands for sulphur.
Claim 6
Dependent Claim
16 words
A compound of the formula I of claim 1 in which Q 1 stands for oxygen.
Claim 7
Dependent Claim
16 words
A compound of the formula I of claim 1 in which Q 2 stands for oxygen.
Claim 8
Dependent Claim
21 words
A compound of the formula I of claim 1 in which Q 1 and Q 2 stand for the group ##STR20##
Claim 9
Dependent Claim
20 words
A compound of formula I of claim 1 in which the bond between C-24 and C-25 is a double bond.
Claim 10
Dependent Claim
20 words
A compound of formula I of claim 1 in which the bond between C-24 and C-25 is a single bond.
Claim 11
Dependent Claim
32 words
A compound of the formula I of claim 1 in which R 1 stands for an alkyl radical substituted with a member selected from the group consisting of halogen, hydroxy, and amino.
Claim 12
Dependent Claim
36 words
A compound of the formula I of claim 1, in which R 1 stands for phenyl-lower alkyl or phenyl radical substituted with one or two members selected from the group consisting of halogen, and lower alkyl.
Claim 13
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-phenylthiofusida-13(17),24-dien-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 14
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-(4'-bromophenylthio)fusida-13(17),24-dien-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 15
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-isopropylthiofusida-13(17), 24-dien-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable as defined in claim 1.
Claim 16
Dependent Claim
18 words
3α,11α-Dihydroxy-16β-tert-butylthiofusida-13(17), 24-dien-21-oic acid, pharmaceutically acceptable, non-toxic or satls and easily esters hydrolysable thereof as defined in claim 1.
Claim 17
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-allylthiofusida-13(17),24-diene-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 18
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-furfurylthiofusida-13(17),24-dien-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 19
Dependent Claim
18 words
3α,11α-Dihydroxy-16β-ethythiofusida-13(17), 24-dien-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 20
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-isopropylthiofusida-13(17)-en-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 21
Dependent Claim
17 words
3α,11α-Dihydroxy-16β-phenylthiofusida-13(17)-en-21-oic acid, and pharmaceutically acceptable, non-toxic salts or easily esters hydrolysable thereof as defined in claim 1.
Claim 22
Dependent Claim
9 words
The pure isomers of the acid of claim 12.
Claim 23
Dependent Claim
9 words
The pure isomers of the acid of claim 14.
Claim 24
Dependent Claim
121 words
Method for producing a compound of formula I of claim 1, in which a compound of formula II, ##STR21## in which formula Q 1 ' stands for Q 1 as defined above or for ##STR22## R 3 representing an alkanoyl, an aralkanoyl or an aroyl radical; R 1 , A, Q 2 and the dotted line between C-24 and C-25 have the meaning as defined above; and R 2 represents a benzyl radical or a substituted benzyl radical, is reacted with an inorganic or organic base in the presence of an organic solvent to form a compound of formula I, which is recovered in the form of an acid, or salt or an easily hydrolysable ester as defined in claim 1.
Claim 25
Dependent Claim
31 words
Method for separating the two possible C-20-isomers of a compound of formula I of claim 1, in which a mixture of the two pure isomers is subjected to a fractionate crystallization.
Claim 26
Dependent Claim
12 words
Method of claim 24, in which the separation is performed by chromatography.
Claim 27
Dependent Claim
65 words
A pharmaceutical preparation in dosage unit form for the enteral or parenteral treatment of patients suffering from bacterial infectious diseases, which comprises as an active ingredient at least one compound of formula I, or a pharmaceutically acceptable, non-toxic salt or an easily hydrolysable ester thereof, and an atoxic pharmaceutically acceptable carrier, the quantity of the said active compound being between 0.05 g and 1 g.
Claim 28
Dependent Claim
65 words
A pharmaceutical preparation in dosage unit form for the enteral or parenteral treatment of patients suffering from bacterial infectious diseases, which comprises as an active ingredient at least one compound of formula I, or a pharmaceutically acceptable, non-toxic salt or an easily hydrolysable ester thereof, and an atoxic pharmaceutically acceptable carrier, the quantity of the said active compound being between 0.05 g and 1 g.
Claim 29
Dependent Claim
37 words
A preparation as claimed in claim 26 wherein the dosage unit contains from 0.25 g to 0.75 g of at least one compound of formula I or a salt or ester thereof as defined in claim 1.
Claim 30
Dependent Claim
18 words
A preparation as claimed in claim 26 wherein the dosage unit is in the form of a tablet.
Claim 31
Dependent Claim
18 words
A preparation as claimed in claim 26 wherein the dosage unit is in the form of a capsule.
Claim 32
Dependent Claim
50 words
A parenteral pharmaceutical preparation in dosage unit form, containing from 0.05 g to 1 g of at least one compound of formula I of claim 1 or a salt or ester thereof as defined in claim 1 as dry matter, in an ampoule, vial or other suitable receptacle, for reconstitution.
Claim 33
Dependent Claim
15 words
A preparation according to claim 26, dissolved or suspendend in a non-toxic, pharmaceutically acceptable vehicle.
Claim 34
Dependent Claim
39 words
A pharmaceutical preparation for oral treatment in form of a sustained-release preparation in dosage unit form of at least one compound of claim 1, in which the dose of the active compound is between 0.05 g to 1 g.
Claim 35
Dependent Claim
43 words
A preparation for oral treatment in the form of a suspension of at least one compound of formula I as such or of a sparingly soluble salt or ester, said preparation containing from 20 to 100 mg per ml of a non-aqueous vehicle.
Claim 36
Dependent Claim
43 words
A preparation for oral treatment in the form of a suspension of at least one compound of formula I as such or of a sparingly soluble salt or ester, said preparation containing from 20 to 100 mg per ml of a non-aqueous vehicle.
Claim 37
Dependent Claim
50 words
A preparation for topical treatment in the form of a powder or an ointment or cream containing at least one compound of formula I or a salt or ester as defined in claim 1 in an amount of from 1/2 g to 10 g per 100 g of the preparation
Claim 38
Dependent Claim
34 words
A preparation according to claim 26 in which the dosage unit additionally contains an antibiotic selected from the group consisting of fusidic acid, fusidic acid derivatives, β-lactam antibiotics, tetracyclines, rifamycins, erythromycin, lycomycin, and clindamycin.
Claim 39
Dependent Claim
34 words
A preparation according to claim 35 which in addition to at least one compound of formula I or a salt or an ester thereof as defined in claim 1 contains a penicillanic acid antibiotic.
Claim 40
Dependent Claim
34 words
A preparation according to claim 35 which in addition to at least one compound of formula I or a salt or an ester thereof as defined in claim 1 contains a cephalosporanic acid antibiotic.
Claim 41
Dependent Claim
44 words
A preparation according to claim 35 which in addition to at least one compound of formula I or a salt or an ester thereof as defined in claim 1 contains a fusidic acid antibiotic different from a compound of formula I of claim 1.
Claim 42
Dependent Claim
33 words
A preparation according to claim 35 which in addition to at least one compound of formula I or a salt or an ester thereof as defined in claim 1 contains a tetracycline antibiotic.
Claim 43
Dependent Claim
48 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to (adult) patients from 0.25 to 100 mg per day of at least one compound of formula I of claim 1 or an equivalent amount of a salt or ester thereof as defined in claim 1.
Claim 44
Dependent Claim
16 words
A method according to claim 40, in which a preparation according to claim 26 is used.
Claim 45
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 27.
Claim 46
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 28.
Claim 47
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 29.
Claim 48
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 30.
Claim 49
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 31.
Claim 50
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 32.
Claim 51
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 33.
Claim 52
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 34.
Claim 53
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 35.
Claim 54
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 36.
Claim 55
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 37.
Claim 56
Dependent Claim
29 words
A method of treating patients suffering from bacterial infectious diseases,, comprising administering to adult patients from 0.25 to 100 mg per day of a preparation according to claim 38.
References Cited (Backward Citations)
US3867413A
Cited
US4004004A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-07-10 | 1982-01-09 | 1982-07-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-07-10 | 1986-01-09 | 1986-07-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-07-10 | 1990-01-09 | 1990-07-11 | $7700.00 | Window Closed / Lapsed |