Alkylthio alkyl avermectins are active antiparasitic agents

• US 5,229,415 A
• Filed: 03/24/1992
• Issued: 07/20/1993
• Est. Priority Date: 03/24/1992
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Linn, Bruce O., Mrozik, Helmut
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Peselev, Elli
• Application Number:
  US07/857,035
• Time in Patent Office: 483 Days
• Field of Search: 549/264, 549/265, 514/450, 514/30, 536/7.1
• US Class Current: 514/450
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: C07H 19/01 sharing oxygen

Abstract

Avermectin compounds are substituted at the 4", 4'"'"' or 13-postion hydroxy group with an alkylthioalkyl group and are optionally substituted at the other reactive positions of the avermectin molecule. The compounds are prepared by reacting protected avermectins, avermectin monosaccharides or avermectin aglycones with dialkylsulfoxides. The compounds are potent antiparasitic agents and compositions for such uses are also disclosed.

Claims

1. A compound having the formula ##STR4## where:

n is 0;

A is single or double bond;

R₁ is present only when A is a single bond and is H, OH, ═

O, ═

NOCH₃ or halogen;

R₂ is C₁ -C₆ alkyl, C₂ -C₆ alkenyl, C₃ -C₈ cycloalkyl, C₄ -C₈ cycloalkenyl, phenyl, furyl or thienyl;

R₃ is OH or ═

NOH;

B is a single or double bond;

R₅ is present only when B is a single bond and is H, OH or halogen;

R₄ is ##STR5## and R₆ is hydrogen or C₁ -C₃ alkyl.

2. A compound of claim 1 where

A is a single bond;

R₁ is H, OH or ═

O;

R₂ is C₁ -C₆ alkyl or C₃ -C₈ cycloalkyl;

R₃ is OH;

B is a double bond; and

R₆ is hydrogen or methyl.

3. A compound of claim 2 where

A is a single bond;

R₁ is H or OH;

R₂ is C₃ -C₄ alkyl or C₅ -C₆ cycloalkyl;

R₃ is OH;

B is a double bond; and

R₆ is hydrogen.

4. A compound of claim 1 which is selected from the group consisting of

13-O-Methylthiomethyl-22,23-dihydroavermectin B1 aglycone;

13-Epi-O-methylthiomethyl-22,23-dihydroavermectin B1 aglycone;

13-O-Methylthiomethyl avermectin B1 aglycone;

13-O-Methylthiomethyl-10,11,22,23-tetrahydroavermectin B1 agylcone;

13-O-Methylthiomethyl-10-hydroxy-10,11,22,23-tetrahydroavermectin B1 aglycone; and

13-O-Methylthiomethyl-10-fluoro-10,11,22,23-tetrahydro avermectin B1 aglycone.

5. A method for the treatment of parasitic infections in animals which comprise administering to such animals infected with parasites an effective amount of a compound of claim 1.

6. A method for the treatment of parasitic infections of plants, soil or premises which comprise applying to such plants, soil or premises infected with parasites an effective amount of a compound of claim 1.

7. A composition useful for the treatment of parasitic infections of animals or parasitic infestations of plants, soil or premises which comprise an inert carrier and an effective amount of a compound of claim 1.