Tetracycline compounds for treatment of
View Patent ↗Methods and compositions for treating Cryptosporidium parvum related disorders in a mammal are discussed. Several novel tetracycline compounds useful for treating Cryptosporidium parvum related disorders are also included.
1. A method for controlling Cryptosporidium parvum in a mammal wherein the presence of Cryptosporidium parvum results in a Cryptosporidium parvum related disorder in said mammal, comprising administering to said mammal an effective amount of a tetracycline compound, such that Cryptosporidium parvum is controlled in said mammal, wherein said tetracycline compound comprises the following formula (I)
wherein
X is CHC(R 13 Y′Y), CHR 6 , S, NR 6 , or O;
R 2 , R 4 and R 4 ′ are each hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, heterocyclic or heteroaromatic;
R 2′ , R 3 , R 10 , R 11 and R 12 are each hydrogen;
R 5 is hydroxyl, hydrogen, thiol, alkaroyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 8 and R 9 are each independently hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 6 is hydrogen, hydroxyl, halogen, thiol, substituted alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 7 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl or an arylalkyl;
R 13 is hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
Y′ and Y are each independently hydrogen, halogen, hydroxyl, cyano, sulfhydryl, amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the tetracycline compound is selected from the group consisting of:
3. The method of claim 1 , wherein said mammal is immunocompetent.
4. The method of claim 1 , wherein said mammal is immunocompromised.
5. The method of claim 1 , wherein said mammal is a human.
6. The method of claim 5 , wherein said human has an immunodeficiency.
7. The method of claim 5 , wherein said human has AIDS.
8. The method of claim 5 , wherein said human has undergone chemotherapy.
9. The method of claim 1 , wherein said Cryptosporidium parvum related disorder is diarrhea.
10. The method of claim 1 , wherein said Cryptosporidium parvum related disorder is cryptosporidiosis.
11. A method for treating a Cryptosporidium parvum related disorder in a mammal, comprising administering to said mammal an effective amount of a tetracycline compound, wherein said tetracycline compound comprises the following formula (I)
wherein
X is CHC(R 13 Y′Y), CHR 6 , S, NR 6 , or O;
R 2 , R 4 and R 4′ are each hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, heterocyclic or heteroaromatic;
R 2′ , R 3 , R 10 , R 11 and R 12 are each hydrogen;
R 5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 8 and R 9 are each independently hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 6 is hydrogen, hydroxyl, halogen, thiol, substituted alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
R 7 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl or an arylalkyl;
R 13 is hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
Y′ and Y are each independently hydrogen, halogen, hydroxyl, cyano, sulfhydryl, amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl; or a pharmaceutically acceptable salt thereof, such that said mammal is treated for said disorder.
12. The method of claim 11 , wherein said mammal is immunocompetent.
13. The method of claim 11 , wherein said mammal is immunocompromised.
14. The method of claim 11 , wherein said mammal is a human.
15. The method of claim 14 , wherein said human has an immunodeficiency.
16. The method of claim 14 , wherein said human has AIDS.
17. The method of claim 14 , wherein said human has undergone chemotherapy.
18. The method of claim 11 , wherein said Cryptosporidium parvum related disorder is diarrhea.
19. The method of claim 11 , wherein said Cryptosporidium parvum related disorder is cryptosporidiosis.
20. The method of claim 11 , further comprising the administration of a pharmaceutically acceptable carrier.
21. The method of claim 11 , further comprising the administration of a supplementary anti- Cryptosporidium parvum agent.
22. The method of claim 21 , wherein said supplementary agent is paromomycin.
23. The method of claim 11 , wherein said tetracycline compound is selected from the group consisting of 5-propionyl-6-cyclopentylsulfanylmethyl doxycycline; thiatetracycline; 6-cyclopentylsulfanylmethyl doxycycline and pharmaceutically acceptable salts thereof.