Avermectin derivatives

• US 4,895,837 A
• Filed: 01/13/1989
• Issued: 01/23/1990
• Est. Priority Date: 01/29/1988
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Mrozik, Helmut, Waksmunski, Frank S.
• Primary Examiner(s): Lilling, Herbert J.
• Assistant Examiner(s): Peselev, Elli
• Application Number:
  US07/296,172
• Time in Patent Office: 375 Days
• Field of Search: 536/7.1, 514/30, 514/450, 549/264, 71/88
• 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 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: C07H 19/01 sharing oxygen

Abstract

There are disclosed novel avermectin Δ 23,24-derivatives (also referred to as 23,24-dehydro compounds). The compounds are prepared by selective dehydration of avermectin A2 or B2 compounds. The 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 Δ 23,24-avermectin compounds have increased activity relative to the A2 or B2 compounds.

Claims

1. A compound having the formula:

##STR7## wherein A represents a single bond or a double bond;

R₁ is iso-propyl or sec-butyl;

R₂ is hydroxy, oxo, loweralkoxy, or triloweralkylsilyl substituted hydroxy;

R₃ is hydrogen, hydroxy, halogen, or oxo or triloweralkylsilyl substituted hydroxy, however R₃ is present only when A represent a single bond;

R₄ is hydrogen, hydroxy, halogen, triloweralkylsilyl substituted hydroxy, ##STR8## R₅ is hydroxy, triloweralkylsilyl substituted hydroxy, oxo, -NR₆ R₇ or ##STR9## R₆ and R₇ are independently hydrogen, loweralkyl, or loweralkanoyl.

2. The compound of claim 1 wherein A is a single or a double bond;

R₁ is isopropyl or sec-butyl;

R₂ is hydroxy;

R₃ is hydrogen, halogen, hydroxy or oxo;

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

-oleandrosyloxy), 4"-R₅ -[(α

-L-oleandrosyl)-α

-L-(oleandrosyloxy)]; and

R₅ is hydroxy, amino, loweralkylamino or diloweralkylamino.

3. The compound of claim 1 where R₁, R₂ and R₃ are as defined in claim 1 and R₄ is halogen.

4. The compound of claim 3 where R₄ is fluorine.

5. The compound of claim 1 selected from the group consisting of 23,24-dehydro avermectin B2a and B2b.

6. The compound of claim 1 selected from the group consisting of 23,24-dehydro avermectin A2a and A2b.

7. The compound of claim 1 selected from the group consisting of 23,24-dehydro-13-deoxy avermectin B2a and B2b aglycone.

8. The compound of claim 1 selected from the group consisting of 23,24-dehydro-10.11-dihydro-10-fluoroavermectin B2a and B2b.

9. The compound of claim 1 selected from the group consisting of 23,24-dehydro-4"-deoxy-4"-methylamino-avermectin B2a and B2b.

10. The compound of claim 1 selected from the group consisting of 4"-oxo-23,24-dehydro avermactin B2a and B2b 4-methyl semicarbazone.

11. The compound of claim 1 selected from the group consisting of 23,24-dehydro-13-deoxy-13-fluoro avermectin B2a and B2b aglycone.

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

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

14. A method for the treatment of insect pests of plants which comprises applying to plants infected with such insect pests or the soil in which they grow, an effective amount of a compound of claim 1.

15. A process for the preparation of the compounds of claim 1 which comprises treating a compound having the formula:

##STR10## wherein A, R₁, R₂, R₃ and R₄ are as defined in claim 1, with diethylamino sulfurtrifluoride initially at from -50°

to -100°

C. followed by reaction at room temperature.