7-substituted fused ring tetracycline compounds
7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted fused ring tetracycline compounds are described.
1. A method for synthesizing a compound of formula (I),
comprising contacting a 7-iodo tetracycline compound with palladium catalyst and a boronic acid of the formula:
wherein
X is CR 6 R 6′ ;
R 4 and R 4′ are each alkyl;
R 5 is hydrogen, hydroxyl, or a prodrug moiety;
R 6 and R 6′ are each independently hydrogen, hydroxyl, alkyl, or taken together, alkenyl;
Y and Y′ are each O;
m is 1 or 2; or a pharmaceutically acceptable salt thereof,
such that a compound of formula (I) is synthesized.
2. The method of claim 1 , wherein R 5 , R 6 , and R 6′ are each hydrogen and R 4 and R 4′ are each methyl.
3. The method of claim 1 , wherein m is 1.
4. The method of claim 1 , wherein said compound of formula (I) is 7-(3′,4′-methylene dioxyphenyl)sancycline.
5. The method of claim 1 , wherein said 7-iodo tetracycline compound is 7-iodosancycline.
6. The method of claim 1 , wherein said palladium catalyst is Pd(OAc) 2 .