Claims
- 1. A compound of the formula whereinR1-R5 are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aryl, halogen, —CN, —NO2, —CO2R6, —COR6, —OR6, —SR6, —SOR6, —SO2R6, —CONR7R8, —NR6N(R7R8), —N(R7R8) or W—Y—(CH2)n—Z; R6 and R7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, or aryl; A is a six membered ring containing one nitrogen; W is O, NR6, or is absent; Y is —(CO)— or —(CO2)—, or is absent; Z is alkyl of 1 to 4 carbon atoms, —CN, —CO2R6, COR6, —CONR7R8, —OCOR6, —NR6COR7, —OCONR6, —OR6, —SR6, —SOR6, —SO2R6, SR6N(R7R8), —N(R7R8) or phenyl; G is a five membered ring containing an oxygen, sulfur, or nitrogen; X is a bond, and n is an integer from 1 to 6; or a pharmaceutical salt thereof.
- 2. A compound of claim 1 wherein at least one of R1-R5 is not hydrogen.
- 3. A compound of claim 1 wherein R1-R5 are, independently selected from hydrogen, alkoxy of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms and halogen.
- 4. A compound of claim 1 wherein A is unsubstituted.
- 5. A compound of claim 1 wherein G is furyl, thiazolyl, or thiadiazolyl.
- 6. A compound of claim 1 wherein G is 2-furyl.
- 7. A compound of claim 1 wherein G is 1,2,3 thiadiazolyl.
- 8. A compound of claim 1 wherein G is 1,3-thiazolyl.
- 9. A pharmaceutical composition comprising a compound of the formula whereinR1-R5 are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aryl, halogen, —CN, —NO2, —CO2R6, —COR6, —OR6, —SR6, —SOR6, —SO2R6, —CONR7R8, —NR6N(R7R8), —N(R7R8) or W—Y—(CH2)n—Z; R6 and R7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms or aryl; A is a six membered ring containing one nitrogen; W is O, NR6, or is absent; Y is —(CO)— or —(CO2)—, or is absent; Z is alkyl of 1 to 4 carbon atoms, —CN, —CO2R6, COR6, —CONR7R8, —OCOR6, —NR6COR7, —OCONR6, —OR6, —SR6, —SOR6, —SO2R6, SR6N(R7R8), —N(R7R8) or phenyl; G is a five membered ring containing an oxygen, sulfur, or nitrogen; X is a bond, and n is an integer from 1 to 6; or a pharmaceutical salt thereof and a pharmaceutically acceptable carrier or diluent.
- 10. A method of inhibiting the replication of a herpes virus comprising contacting a compound of the formula whereinR1-R5 are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aryl, halogen, —CN, —NO2, —CO2R6, —COR6, —OR6, —SR6, —SOR6, —SO2R6, —CONR7R8, —NR6N(R7R8), —N(R7R8) or W—Y—(CH2)n—Z; R6 and R7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, or aryl; A is a six membered ring containing one nitrogen; W is O, NR6, or is absent; Y is —(CO)— or —(CO2)—, or is absent; Z is alkyl of 1 to 4 carbon atoms, —CN, —CO2R6, COR6, —CONR7R8, —OCOR6, —NR6COR7, —OCONR6, —OR6, —SR6, —SOR6, —SO2R6, SR6N(R7R8), —N(R7P8) or phenyl; G is a five membered ring containing an oxygen, sulfur, or nitrogen; X is a bond, and n is an integer from 1 to 6; or a pharmaceutical salt thereof, with a herpes virus.
- 11. The method of claim 10 wherein the herpes virus is human cytomegalovirus.
- 12. The method of claim 10 wherein the herpes virus is herpes simplex virus.
- 13. The method of claim 10 where the herpes virus is varicella zoster virus.
- 14. The method of claim 13 wherein the varicella zoster virus is treated with substantially pure (S) optical isomer.
- 15. A method of treating a patient suffering from a herpes virus infection comprising administering to the patient a therapeutically effective amount of a compound having the formula whereinR1-R5 are independently selected from hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aryl, halogen, —CN, —NO2, —CO2R6, —COR6, —OR6, —SR6, —SOR6, —SO2R6, —CONR7R8, —NR6N(R7R8), —N(R7R8) or W—Y—(CH2)n—Z; R6 and R7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, or aryl; A is a six membered ring containing one nitrogen; W is O, NR6, or is absent; Y is —(CO)— or —(CO2)—, or is absent; Z is alkyl of 1 to 4 carbon atoms, —CN, —CO2R6, COR6, —CONR7R8, —OCOR6, —NR6COR7, —OCONR6, —OR6, —SR6, —SOR6, —SO2R6, SR6N(R7R8), —N(R7R8) or phenyl; G is a five membered ring containing an oxygen, sulfur, or nitrogen; X is a bond, and n is an integer from 1 to 6; or a pharmaceutical salt thereof.
- 16. The method of claim 15 wherein the herpes virus is human cytomegalovirus.
- 17. The method of claim 15 wherein the herpes virus is herpes simplex virus.
- 18. The method of claim 15 where the herpes virus is varicella zoster virus.
- 19. The method of claim 18 where the varicella zoster virus is treated with substantially pure (S) optical isomer.
- 20. A compound of claim 1 selected from:Furan-2-carboxylic acid {5-[3-(5-chloro-2,4-dimethoxy-phenyl)-thioureido]-pyridin-2-yl}-amide, [1,2,3]Thiadiazole-4-carboxylic acid {5-[3-(5-chloro-2,4-dimethoxy-phenyl)-thioureido]-pyridin-2-yl}-amide, Furan-2-carboxylic acid {6-[3-(5-chloro-2,4-dimethoxy-phenyl)-thioureido]-pyridin-3-yl}-amide, [1,2,3]Thiadiazole-4-carboxylic acid {6-[3-(5-chloro-2,4-dimethoxy-phenyl)-thioureido]-pyridin-3-yl}-amide, and [1,2,3]Thiadiazole-4-carboxylic acid {5-[3-(3,5-dichloro-phenyl)-thioureido]-pyridin-2-yl}-amide; and pharmaceutical salts thereof.
Parent Case Info
This application is a divisional application of U.S. Ser. No. 09/44,782, filed Nov. 22, 1999 now U.S. Pat No. 6,166,028 which benefit of prior U.S. Provisional application Nos. 60/150,698, 60/155,240, 60/155,192, 60/160,692, 60/228,808, 60/288,805, 60/288,809, and U.S. application Ser. Nos. 09/208,540, 09/208,164, and 09/208,561 filed Dec. 9, 1998. These applications are herein incorporated by reference in their entireties.
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Provisional Applications (7)
|
Number |
Date |
Country |
|
60/150698 |
Dec 1998 |
US |
|
60/155240 |
Dec 1998 |
US |
|
60/228808 |
Dec 1998 |
US |
|
60/228805 |
Dec 1998 |
US |
|
60/155192 |
Dec 1998 |
US |
|
60/150692 |
Dec 1998 |
US |
|
60/228809 |
Dec 1998 |
US |
Patent Grant
6407123
