US4056616A
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Rosamicin derivatives and method of using same
Assignee: Merck Sharp & Dohme LLC
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Filing: 1976-03-05
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Granted: 1977-11-01
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Expires: 1996-03-05
Abstract
Abstract Rosamicin is an antibiotic elaborated by Micromonospora rosaria. The compounds described herein are antibacterial derivatives of rosamicin. Also described are processes for the preparation of these antibacterial derivatives from rosamicin.
Inventors
- 👤 Hans Reimann
- 👤 Robert S. Jaret
- 👤 Mohammad Mehdi Nafissi-Varchei
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 21:14
CPC Classifications
C; C07; C07H; C07H17/00; C07H17/04; C07H17/08
Claims Analysis
Total Claims: 53
Claim 1
Independent Claim
225 words
A compound of the formulae: ##STR7## and the non-toxic pharmaceutically acceptable acid addition salts thereof wherein the dotted lines represent facultative double bonds; Q is a member selected from the group consisting of O, and ##STR8## Z is a member selected from the group consisting of O, ##STR9## NOR' and NOR"; R and R' are members selected from the group consisting of hydrogen and hydrocarbon carbonyl having 2 to 18 carbon atoms; R" is hydrogen or alkyl having 1 to 5 carbon atoms; B together with the carbon atoms of positions 12 and 13 to which it is attached represents a single bond or a double bond or, when Q or Z is other than O, or when the macrolide ring is saturated between positions 10 and 11 or unsaturated between positions 2 and 3, B may also be an oxirane ring; and W is a member selected from the group consisting of OR' and hydrogen, R' being as previously defined with the proviso that when W is hydrogen, positions 2 and 3 are connected by a double bond, and the further proviso that in formula II, when B, together with the carbon atoms to which it is attached represents a double bond, W is OR', Q is O, and positions 10 and 11 are connected by a double bond, Z is other than ##STR10##
Claim 2
Dependent Claim
225 words
A compound of the formulae: ##STR7## and the non-toxic pharmaceutically acceptable acid addition salts thereof wherein the dotted lines represent facultative double bonds; Q is a member selected from the group consisting of O, and ##STR8## Z is a member selected from the group consisting of O, ##STR9## NOR' and NOR"; R and R' are members selected from the group consisting of hydrogen and hydrocarbon carbonyl having 2 to 18 carbon atoms; R" is hydrogen or alkyl having 1 to 5 carbon atoms; B together with the carbon atoms of positions 12 and 13 to which it is attached represents a single bond or a double bond or, when Q or Z is other than O, or when the macrolide ring is saturated between positions 10 and 11 or unsaturated between positions 2 and 3, B may also be an oxirane ring; and W is a member selected from the group consisting of OR' and hydrogen, R' being as previously defined with the proviso that when W is hydrogen, positions 2 and 3 are connected by a double bond, and the further proviso that in formula II, when B, together with the carbon atoms to which it is attached represents a double bond, W is OR', Q is O, and positions 10 and 11 are connected by a double bond, Z is other than ##STR10##
Claim 3
Dependent Claim
20 words
A compound of claim 1 of the formula: ##STR11## wherein Z, R, and R' are as defined in claim 1.
Claim 4
Dependent Claim
37 words
A compound of claim 1, formula II, having the formula: ##STR12## wherein Q, Z, R and R' are as defined in said claim 1, with the proviso that when Q is O, Z is other than ##STR13##
Claim 5
Dependent Claim
20 words
A compound of claim 1 of the formula: ##STR14## wherein Q,Z,R and R' are as defined in said claim 1.
Claim 6
Dependent Claim
21 words
A compond of claim 1 of the formula: ##STR15## wherein Q,Z, R and R' are as defined in said claim 1.
Claim 7
Dependent Claim
20 words
A compound of claim 1 of the formula: ##STR16## wherein Q,Z and R are as defined in said claim 1.
Claim 8
Dependent Claim
21 words
A compound of claim 1 of the formula: ##STR17## wherein Q, Z and R are as defined in said claim 1.
Claim 9
Dependent Claim
11 words
A non-toxic acid addition salt of a compound of claim 2.
Claim 10
Dependent Claim
14 words
A compound of claim 8, said compound being the lauryl sulfate salt of 12,13-desepoxy-10,11-dihydrorosamicin.
Claim 11
Dependent Claim
22 words
The compound of claim 2 wherein Q is ##STR18## R and R' are hydrogen and Z is O, said compound being 9-dihydro-12,13-desepoxy-10,11-dihydrorosamicin.
Claim 12
Dependent Claim
18 words
A compound of claim 2 wherein Q is ##STR19## R and R' are hydrogen and Z is ##STR20##
Claim 13
Dependent Claim
13 words
The compound of claim 11 wherein Z is ##STR21## said compound being 9-dihydro-12,13-desepoxy-10,11-dihydrorosamicin-20-dimethylacetal.
Claim 14
Dependent Claim
18 words
A compound of claim 2 wherein Q is O, R and R' are hydrogen and Z is ##STR22##
Claim 15
Dependent Claim
13 words
The compound of claim 13, wherein Z is ##STR23## said compound being 12,13-desepoxy-10,11-dihydrorosamicin-20-dimethylacetal.
Claim 16
Dependent Claim
20 words
A compound of claim 3, wherein Q and Z are O, R and R' are hydrogen, said compound being 12,13-desepoxy-12,13-dehydrorosamicin.
Claim 17
Dependent Claim
11 words
A non-toxic acid addition salt of a compound of claim 15.
Claim 18
Dependent Claim
17 words
A compound of claim 16 wherein the acid is stearic acid, said compound being 12,13-desepoxy-12,13-dehydrorosamicin stearate salt.
Claim 19
Dependent Claim
21 words
A compound of claim 16 wherein the acid is phosphoric acid monopotassium salt, said compound being 12,13-desepoxy-12,13-dehydrorosamicin potassium dihydrogen phosphate salt.
Claim 20
Dependent Claim
14 words
A compound of claim 16, said compound being the lauryl sulfate salt of 12,13-desepoxy-12,13-dehydrorosamicin.
Claim 21
Dependent Claim
21 words
A compound of claim 3 wherein Q is ##STR24## Z is O, R and R' are hydrogen, said compound being 9-dihydro-12,13-desepoxy-12,13-dehydrorosamicin.
Claim 22
Dependent Claim
25 words
A compound of claim 3 wherein R is hydrocarbon carbonyl having 2 to 18 carbon atoms, R' is hydrogen, and Q and Z are O.
Claim 23
Dependent Claim
14 words
The compound of claim 21 wherein R is propionyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 2'-propionate.
Claim 24
Dependent Claim
14 words
The compound of claim 21 wherein R is acetyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 2'-acetate.
Claim 25
Dependent Claim
14 words
The compound of claim 21 wherein R is benzoyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 2'-benzoate.
Claim 26
Dependent Claim
14 words
The compound of claim 21 wherein R is steroyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 2'-stearate.
Claim 27
Dependent Claim
24 words
A compound of claim 3 wherein R and R' are hydrocarbon carbonyls having 2 to 18 carbon atoms and Q and Z are O.
Claim 28
Dependent Claim
16 words
The compound of claim 26 wherein R and R' are acetyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 3,2'-diacetate.
Claim 29
Dependent Claim
25 words
A compound of claim 3 wherein R is hydrogen, R' is hydrocarbon carbonyl having 2 to 18 carbon atoms and Q and Z are O.
Claim 30
Dependent Claim
14 words
The compound of claim 28 wherein R' is acetyl, said compound being 12,13-desepoxy-12,13-dehydrorosamicin 3-acetate.
Claim 31
Dependent Claim
30 words
A compound of claim 4 wherein Q is O; R and R' are hydrogen and positions 10 and 11 are joined by a single bond, said compound being 10, 11-dihydrorosamicin.
Claim 32
Dependent Claim
20 words
A compound of claim 4 wherein Q, R and R' are as defined in said claim and Z is ##STR25##
Claim 33
Dependent Claim
29 words
The compound of claim 31 wherein Q is O; R and R' are hydrogen and positions 10 and 11 are joined by a double bond, said compound being 20-dihydrorosamicin.
Claim 34
Dependent Claim
34 words
The compound of claim 4 wherein Q is O; R and R' are acetyl and Z is ##STR26## and positions 10 and 11 are joined by a double bond, said compound being 20-dihyrorosamicin-3, 20,2'-triacetate.
Claim 35
Dependent Claim
30 words
A compound of claim 4 wherein Q, R, and R' are as defined in said claim, Z is NOR" and positions 10 and 11 are joined by a double bond.
Claim 36
Dependent Claim
19 words
The compound of claim 34 wherein Q is O; R, R' and R" are hydrogen, said compound being rosamicin-20-oxime.
Claim 37
Dependent Claim
30 words
A compound of claim 4 wherein Q, R, and R' are as defined in said claim, Z is ##STR27## and positions 10 and 11 are joined by a double bond.
Claim 38
Dependent Claim
22 words
The compound of claim 36 wherein Q is O; R and R' are hydrogen and R" is methyl, said compound being rosamicin-20-dimethylacetal.
Claim 39
Dependent Claim
22 words
The compound of claim 36 wherein Q is ##STR28## R and R' are hydrogen and R" is methyl, said compound being 9-dihydrorosamicin-20-dimethylacetal.
Claim 40
Dependent Claim
19 words
A compound of claim 4 wherein Q is ##STR29## Z, R and R' are as defined in said claim.
Claim 41
Dependent Claim
18 words
The compound of claim 39 wherein Z is O, R and R' are hydrogen, said compound being 9-dihydrorosamicin.
Claim 42
Dependent Claim
21 words
A compound of claim 5 wherein Q and Z are O and R and R' are as defined in said claim.
Claim 43
Dependent Claim
15 words
The compound of claim 41 wherein R and R' are hydrogen, said compound being 10,11-dihydroxy-10,11-dihydrorosamicin.
Claim 44
Dependent Claim
19 words
A compound of claim 6 wherein Q and Z are O and R is as defined in said claim.
Claim 45
Dependent Claim
13 words
The compound of claim 43, wherein R is hydrogen, said compound being 2,3:12,13-bisdehydro-3-deoxy-12,13-desepoxy-rosamicin.
Claim 46
Dependent Claim
19 words
A compound of claim 7 wherein Q and Z are O and R is as defined in said claim.
Claim 47
Dependent Claim
13 words
The compound of claim 45 wherein R is hydrogen, said compound being 2,3-dehydro-3-deoxyrosamicin.
Claim 48
Independent Claim
246 words
A method of eliciting an antibacterial response which comprises administering to a warm-blooded animal having a bacterial infection a therapeutically effective quantity of a compound of the formulae: ##STR30## the non-toxic pharmaceutically acceptable acid addition salts thereof wherein the dotted lines represent facultative double bonds; Q is a member selected from the group consisting of O, and ##STR31## Z is a member selected from the group consisting of O, ##STR32## NOR' and NOR"; R and R' are members selected from the group consisting of hydrogen and hydrocarbon carbonyl having 2 to 18 carbon atoms; R" is hydrogen or alkyl having 1 to 5 carbon atoms; B together wtih the carbon atoms of positions 12 and 13 to which it is attached represents a single bond or a double bond or, when Q or Z is other than O, or when the macrolide ring is saturated between positions 10 and 11 or unsaturated between positions 2 and 3, B may also be an oxirane ring; and W is a member selected from the group consisting of OR' and hydrogen, R' being as previously defined with the proviso that when W is hydrogen, positions 2 and 3 are connected by a double bond, and the further proviso that in formula II, when B, together with the carbon atoms which it is attached represents a double bond, W is OR', Q is O, and positions 10 and 11 are connected by a double bond, Z is other than ##STR33##
Claim 49
Independent Claim
246 words
A method of eliciting an antibacterial response which comprises administering to a warm-blooded animal having a bacterial infection a therapeutically effective quantity of a compound of the formulae: ##STR30## the non-toxic pharmaceutically acceptable acid addition salts thereof wherein the dotted lines represent facultative double bonds; Q is a member selected from the group consisting of O, and ##STR31## Z is a member selected from the group consisting of O, ##STR32## NOR' and NOR"; R and R' are members selected from the group consisting of hydrogen and hydrocarbon carbonyl having 2 to 18 carbon atoms; R" is hydrogen or alkyl having 1 to 5 carbon atoms; B together wtih the carbon atoms of positions 12 and 13 to which it is attached represents a single bond or a double bond or, when Q or Z is other than O, or when the macrolide ring is saturated between positions 10 and 11 or unsaturated between positions 2 and 3, B may also be an oxirane ring; and W is a member selected from the group consisting of OR' and hydrogen, R' being as previously defined with the proviso that when W is hydrogen, positions 2 and 3 are connected by a double bond, and the further proviso that in formula II, when B, together with the carbon atoms which it is attached represents a double bond, W is OR', Q is O, and positions 10 and 11 are connected by a double bond, Z is other than ##STR33##
Claim 50
Dependent Claim
31 words
A method according to claim 47 wherein the compound is administered at a dosage range of from about 5 mg to about 50 mg per kilogram of body weight per day.
Claim 51
Dependent Claim
15 words
A method according to claim 47 wherein the anti-bacterial response is effected by oral administration.
Claim 52
Dependent Claim
15 words
A method according to claim 47 wherein the anti-bacterial response is effected by topical administration.
Claim 53
Dependent Claim
15 words
A method according to claim 47 wherein the anti-bacterial response is effected by parenteral administration.
References Cited (Backward Citations)
US3769273A
Cited
US3975372A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-10-31 | 1981-05-02 | 1981-11-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-10-31 | 1985-05-02 | 1985-11-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-10-31 | 1989-05-02 | 1989-11-01 | $7700.00 | Window Closed / Lapsed |