Avermectin derivatives

• US 5,057,499 A
• Filed: 06/02/1989
• Issued: 10/15/1991
• Est. Priority Date: 06/02/1989
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Sinclair, Peter J., Mrozik, Helmut
• Primary Examiner(s): Peselev, Elli
• Application Number:
  US07/360,621
• Time in Patent Office: 865 Days
• Field of Search: 514/30, 514/450, 536/7.1, 549/264, 549/265
• US Class Current: 514/30
• CPC Class Codes: A01N 43/90 having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: C07H 19/01 sharing oxygen

Abstract

There are disclosed novel avermectin derivatives wherein the outer oleandrose ring of avermectin or avermectin monosaccharide is homologated by addition of diazomethane to 4"- or 4'"'"'-oxo-avermectin to afford the perhydrooxepine derivatives. The homologated avermectins can then be further derivatized to afford additional novel avermectins. The new compounds are potent antiparasitic agents, in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.

Claims

1. A compound having the formula ##STR12## wherein the broken line at the 22,23 position represents a single bond and wherein R₁ is hydrogen or hydroxy or oxo, or the broken line represents a double bond and R₁ is absent;

R₂ is methyl, ethyl, or an alpha-branched C₃ -C₈ alkyl or alkenyl group;

R₃ is hydrogen, loweralkyl or loweralkanoyl;

R₄ is ##STR13## R₅ is ##STR14## R₆ is hydrogen or loweralkoxy;

R₇ is hydroxy, amino, N-loweralkylamino, N,N-diloweralkylamino, or loweralkanoylamino; and

R₈ is hydrogen;

or

R₇ and R₈ together are oxo, methylene, --CH₂ O--, hydroxyimino or semicarbazono;

R₉ is loweralkyl.

2. A compound of claim 1 wherein the broken line at the 22,23 position represents a single bond and wherein R₁ is hydrogen or hydroxy or oxo, or the broken line represents a double bond and R₁ is absent;

R₂ is iso-propyl, sec-butyl, or an alpha-branched C₃ -C₈ alkenyl group;

R₃ is hydrogen;

R₄ is ##STR15## R₅ is ##STR16## R₆ is hydrogen or methoxy;

R₇ is hydroxy, amino, N-loweralkylamino, N,N-diloweralkylamino, or loweralkanoylamino; and

R₈ is hydrogen;

or

R₇ and R₈ together are oxo, methylene, --CH₂ O--, hydroxyimino or semicarbazono;

R₉ is methyl.

3. A compound of claim 1 wherein the broken line at the 22,23 position represents a single bond and wherein R₁ is hydrogen or hydroxy or oxo, or the broken line represents a double bond and R₁ is absent;

R₂ is iso-propyl, sec-butyl, or an alpha-branched C₃ -C₆ alkenyl group;

R₃ is hydrogen;

R₄ is ##STR17## R₅ is ##STR18## R₆ is hydrogen or methoxy;

R₇ is hydroxy, amino, N-loweralkylamino, N,N-diloweralkylamino, or loweralkanoylamino; and

R₈ is hydrogen;

or

R₇ and R₈ together are oxo, methylene, --CH₂ O--, hydroxyimino or semicarbazono;

R₉ is methyl.

4. A compound of claim 1 which is 4'"'"'-O-[2-(4-methoxy-7-methyloxepin-5-onyl)]-avermectin B1a/B1b monosaccharide.

5. A compound of claim 1 which is 4'"'"'-O-[2-(5-exomethylene-4-methoxy-7-methyl-5,5a-oxo-oxepinyl)]-avermectin B1a/B1b monosaccharide.

6. A compound of claim 1 which is 4'"'"'-O-[2-(5-hydroxy-4-methoxy-7-methyl-oxepinyl)]-avermectin B1a/B1b monosaccharide isomer a or isomer b.

7. A compound of claim 1 which is 22,23-dihydro-4"-O-[2-(5-hydroxy-4-methoxy-7-methyl-oxepinyl)]-avermectin B1a/B1b monosaccharide isomer a or b.

8. A compound of claim 1 which is 4'"'"'-O-[2-(7-methyl-oxepin-5-onyl)]-avermectin B1a/B1b monosaccharide.

9. A compound of claim 1 which is 22,23-dihydro-4'"'"'-O-[2-(4-methoxy-7-methyl-oxepin-5-onyl)]-avermectin B1a/B1b monosaccharide.

10. A compound of claim 1 which is 4'"'"'-O-[2-(4-methoxy-7-methyloxepin-5-onyl)]-avermectin B2a/B2b monosaccharide.

11. A compound of claim 1 which is 4'"'"'-O-[2-(5-acetylamino-4-methoxy-7-methyl-oxepinyl)]-avermectin B1a/B1b monosaccharide.

12. A method for the treatment of parasitic diseases of animals which comprises administering to an animal infected with parasites an effective amount of a compound of claim 1.

13. A method for the treatment of parasitic diseases of plants which comprises administering to a plant infected with parasites an effective amount of a compound of claim 1.

14. A composition useful for the treatment of parasitic diseases of plants or animals which comprises an inert carrier and an effective amount of a compound of claim 1.