Reduced avermectin derivatives

• US 4,831,016 A
• Filed: 10/31/1986
• Issued: 05/16/1989
• Est. Priority Date: 10/31/1986
• Status: Expired due to Fees

• Current Assignee: Merck & Company Incorporated Lincoln AVE City of Rahway NJ
• Original Assignee: Merck & Co., Inc.
• Inventors: Shih, Thomas L., Mrozik, Helmut
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): OWENS, AMELIA A
• Application Number:
  US06/925,772
• Time in Patent Office: 928 Days
• Field of Search: 549/264, 549/214, 536/7.1, 514/30, 514/450
• 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: A23K 20/195 Antibiotics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: C07H 19/01 sharing oxygen

Abstract

There are disclosed novel avermectin reduction products. The compounds are prepared by selective catalytic hydrogenation of avermectin-like compounds or by reaction of selected double bonds with electrophylic reagents. The reduced avermectin compounds have utility as anti-parasitic agents and compositions for that use are also disclosed. The compounds are also highly potent insecticides against agricultural pests. The reduced avermectin compounds have increased stability towards light which prolongs their insecticidal activities when applied to field crops subject to irradiation by sunlight.

Claims

1. A compound having the formula:

##STR6## wherein A is a single bond, B and C each represent a double bond, and D represents a single bond or a double bond;

R₁ is hydrogen, hydroxy or a ketone provided that R₁ is present only when D indicates a single bond;

R₂ is methyl, ethyl, iso-propyl or sec-butyl or --C(CH₃)=CHR₁₀ where R₁₀ is methyl, ethyl or isopropyl;

R₃ is hydroxy, loweralkoxy, lower-alkanoyloxy or otherwise protected hydroxy or R₃, together with the adjacent carbon atom and the hydrogen attached thereto, form a carbonyl group;

R₄ is hydrogen, hydroxy, halogen, loweralkoxy, loweralkanoyloxy, ##STR7## R₅ is hydroxy, or --NR₆ R₇ or R₅, together with the adjacent carbon atom and the hydrogen attached thereto, form a carbonyl group;

R₆ and R₇ are independently hydrogen, loweralkyl, or lowerlkanoyl;

R₈ is hydrogen or bromo;

R₉ is hydrogen, halogen, hydroxy, or R₉ together with the adjacent carbon atom and the hydrogen attached thereto, form a carbonyl group; and

the 4" and 5 position trisubstituted silyl protected hydroxy derivatives thereof.

2. The compound of claim 1 wherein A is a single bond and B is a double bond or an epoxide, C is a double bond and D is a single bond or a double bond;

R₁ is hydrogen or hydroxy when D is a single bond;

R₂ is methyl, ethyl, isopropyl or see-butyl;

R₃ is hydroxy;

R₄ is hydrogen, hydroxy, halogen, loweralkoxy, loweralkanoyloxy, 4'"'"'-R₅ -(α

-oleandrosyloxy), 4"-R₅ -[(α

-L-oleandrosyl)-α

-L-(oleandrosyloxy)];

R₅ is hydroxy, amino, loweralkylamino or diloweralkylamino;

R₈ is hydrogen, chloro or bromo; and

R₉ is hydrogen, halogen, hydroxy or oxo.

3. The compound of claim 2 which is 10,11-dihydroavermectin B1a and B1b.

4. The compound of claim 2 which is 10,11,22,23-tetrahydro avermectin B1a and B1b.

5. The compound of claim 2 which is 13-deoxy-10,11,22,23-tetrahydroavermectin B1 1a and B1b aglycone.

6. The compound of claim 2 which is 4"-deoxy-10,11-dihydro-4"-methylamino-10-fluoro avermectin B1a and B1b.

7. The compound of claim 2 which is 4"-methylamino-4"-deoxy-10,11-dihydroavermectin B1a and B1b.

8. The compound of claim 2 which is 10,11-dihydro-10-fluoroavermectin B1a and B1b.

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

10. A composition useful for treating animals infected with parasites or for treating areas infested with insect pests which comprises an inert carrier and a compound of claim 1.

11. A method for the treatment of insect pests which comprises applying to an area infected with such insect pests, an effective amount of a compound of claim 1.