O-sulfate derivatives of avermectins and milbemycins having improved water solubility

• US 4,622,313 A
• Filed: 08/01/1985
• Issued: 11/11/1986
• Est. Priority Date: 08/01/1985
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Wyvratt, Matthew J. Jr.
• Primary Examiner(s): Brown, Johnnie R.
• Assistant Examiner(s): Peselev, Elli
• Application Number:
  US06/761,247
• Time in Patent Office: 467 Days
• Field of Search: 536/7.1, 549/264, 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: C07H 19/01 sharing oxygen

Abstract

There are disclosed novel O-sulfate derivatives of avermectin and milbemycin. The avermectin and milbemycin O-sulfate derivatives have improved water solubility compared to the parent avermectin and milbemycin compounds and have utility as anti-parasitic agents and as potent insecticides against agricultural pests.

Claims

1. A compound having the formula:

##STR6## wherein;

X is ##STR7## R¹ is methyl, ethyl, isopropyl, or sec-butyl;

R² is hydrogen, methyl, or --SO₃.sup.⊖

M.sup.⊕

wherein M is a member selected from the Group I elements Li, Na, K, Rb, Cs and Fr, the Group II Be, Mg, Ca, Sr, Ba and Ra elements or an ammonium, diloweralkyl ammonium, or pyridinium cation;

R³ is hydrogen, hydroxy, --OSO₃.sup.⊖

M.sup.⊕

, α

-L-oleandrosyloxy, 4'"'"'-(O)--SO₃.sup.⊖

M.sup.⊕

-(α

-L-oleandrosyloxy), 4'"'"'-(α

-L-oleandrosyl-α

-L-oleandrosyloxy, 4"-(O)--SO₃.sup.⊖

M.sup.⊕

-4'"'"'-(α

-L-oleandrosyl)-α

-L-oleandrosyloxy, wherein M is as defined above;

provided that one of said R² or R³ groups contains said --SO₃.sup.⊖

M.sup.⊕

or --OSO₃.sup.⊖

M.sup.⊕

substituents; and

, physiologically acceptable salts thereof.

2. A compound of claim 1 which is a member of the group:

sodium 4"-O-sulfate-avermectin B1a;

sodium 4"-O-sulfate-avermectin B1b

sodium 4"-O-sulfate-22,23-dihydroauermectin B1a;

sodium 4"-O-sulfate--22,23-dihydroavermectin B1b;

sodium 4",5-di-O-sulfate-22,23-dihydroavermectin B1a;

sodium 4",5-di-O-sulfate-22,23-dihydroavermectin B1b;

sodium 4",5-di-O-sulfate avermectin B1a;

sodium 4"-5-di-O-sulfate avermectin B1b;

sodium 4'"'"'-O-sulfate-22,23-dihydroavermectin B1b monosaccharide;

sodium 4'"'"'-O-sulfate-22,23-dihydroavermectin B1b monosaccharide;

sodium 4'"'"'-O-sulfate-avermectin Bla[/b] monosaccharide;

sodium 4'"'"'-O-sulfate avermectin B1b monosaccharide;

sodium 5-O-sulfate-13-deoxy-22,23-dihydroavermectin B1a aglycon;

sodium-5-O-sulfate-13-deoxy-22,23-dihydroavermectin B1b aglycon;

sodium 4"-O-sulfate-avermectin A1a;

sodium 4"-O-sulfate avermectin A1b;

sodium 4"-O-sulfate-avermectin B2a; and

sodium 4"-O-sulfate-avermectin B2b.

3. 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.

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

5. A method for treating agricultural plants which comprises contacting plants exposed to pests and parasites with an effective amount of a compound of claim 1.

6. A pharmaceutical composition useful for treating agricultural plants exposed to pests and parasites which comprises an inert carrier and an effective amount of a compound of claim 1.