Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits
OwnerIain W. Duncan, Edward A. Kesicki +3inventors
InventorsIain W. Duncan, Edward A. Kesicki, Carl G. Osborne, William D. Schwieterman, Irina Jacobson
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Abstract
The present disclosure is directed to compositions and methods which utilize the tetracycline scaffold, preferably the scaffold of tetracycline or minocycline, and which significantly lack antibiotic activity. The compounds have neuroprotective attributes without interfering with the drugs capacity to pass through the blood brain barrier. These compounds have neuroprotective activity because of their inhibition of neuronal cell cycle progression. The compounds are characterized in part by a fifth ring joining positions 9 and 10.
Claims6
A compound having the formula:
- where R4, R6 R9, and R10 are defined as follows:
- R4 is a substitution selected from the group consisting of —N(CH3)2, N(CH3)2, NH(CH2 CH2 OH), and amino alkyl, or else R4 is a disubstitution selected from the group consisting of (i) a first substitution of —N(CH3)2 and a second substitution of substituted alkyl, and (ii) a first substitution of amino alkyl and a second substitution of lower alkyl;
- R6 is H or —CH2S—R″, where R″ is aryl or substituted aryl;
- and
- either R9 is H and R10 is OH or lower alkyl, or else
- R10 and R9 taken together have the formula (from R10-R9) (a) —O—Y—HN—, where Y is CH and the bond Y—N is double, (b) —O—Y—HN—, where Y is C═O, or (c) —O—CH2—C(═O)—HN—;
- or a pharmaceutically acceptable salt thereof,
- with the proviso that when R9 is H and R10 is OH or lower alkyl, R6 is not H.
Dependencies are inferred from the claim text.