C-20 steroid compounds, compositions and uses thereof to treat traumatic brain injury (tbi), including concussions
AssigneePrevacus, Inc.
InventorDaniel E. Levy
Life of this patent
Estimating the term…
Abstract
The present invention relates to C-20 steroid compounds, compositions and methods of use thereof to treat, minimize and/or prevent traumatic brain injury (TBI), including severe TBI, moderate TBI and mild TBI, including concussions.
Claims35
A compound of Formula I:
- or a pharmaceutically acceptable salt, ester, prodrug or co-crystal thereof,
- wherein, X is O, N or S;
- Y is O, N or S;
- or, YR8R10 is absent;
- R1, R2, R5, and R6 are independently H, C1-C6 alkyl, halogen, OR12, NR13R14, SR15, SOR16 or SO2R17;
- R4 is H or C1-C6 alkyl;
- R4 together with R3 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- or R4 and R7 together form a double bond;
- R3 is H or C1-C6 alkyl;
- R3 together with R4 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R3 is absent;
- R7 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R7 and R4 together form a double bond;
- R8 is H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- R8 together with R9 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R8 is absent;
- R9 is H or C1-C6 alkyl;
- R9 together with R8 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- R9 and R11 together form a double bond;
- R10 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R10 and R11 together form a double bond;
- R11 is H or C1-C6 alkyl;
- or R11 and R-10 together form a double bond;
- R11 and R9 together form a double bond;
- R12, R13, R14, R15, R16 and R17 are independently H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- and the dotted line indicates the presence of either a single or a double bond wherein the valences of a single bond are completed by hydrogens.
A pharmaceutical composition comprising a therapeutically useful amount of a compound of Formula I
- or a pharmaceutically acceptable salt, ester, prodrug or co-crystal thereof,
- wherein X is O, N or S;
- Y is O, N or S;
- or, YR8R10 is absent;
- R1, R2,
- R5, and R6 are independently H, C1-C6 alkyl, halogen, OR12, NR13R14, SR15, SOR16 or SO2R17;
- R4 is H or C1-C6 alkyl;
- R4 together with R3 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- or
- R4 and R7 together form a double bond;
- R3 is H or C1-C6 alkyl;
- R3 together with R4 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R3 is absent;
- R7 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R7 and R4 together form a double bond;
- R9 is H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- R9 together with R9 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R9 is absent;
- R9 is H or C1-C6 alkyl;
- R9 together with R9 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- R9 and R11 together form a double bond;
- R10 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R10 and R11 together form a double bond;
- R11 is H or C1-C6 alkyl;
- or R11 and R19 together form a double bond;
- R11 and R9 together form a double bond;
- R12, R13, R14, R15, R16 and R17 are independently H, C(O)—C1-C6 alkyl or C1-C6 alkyl;
- and the dotted line indicates the presence of either a single or a double bond wherein the valences of a single bond are completed by hydrogens.
The pharmaceutical composition of claim 27 wherein said pharmaceutical composition further comprises an additional therapeutic agent selected from the classes comprising small molecules, antibodies, proteins and enzymes.
The pharmaceutical composition of claim 28 wherein said additional therapeutic agent is a neuroprotective agent, an anti-inflammatory agent, an anti-amyloid agent or an anti-Tau agent.
The pharmaceutical composition of claim 30 wherein said formulation is a powder, a gel or a solution.
A method for treating, minimizing or preventing TBI in an animal in need of TBI treatment, said method comprising administering to a the animal, an effective amount of a compound of Formula I
- or a pharmaceutically acceptable salt, ester, prodrug or co-crystal thereof,
- wherein X is O, N or S;
- Y is O, N or S;
- or, YR8R10 is absent;
- R1, R2, R5, and R6 are independently H, C1-C6 alkyl, halogen, OR12, NR13R14, SR15, SOR16 or SO2R17;
- R4 is H or C1-C6 alkyl;
- R4 together with R3 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- or
- R4 and R7 together form a double bond;
- R3 is H or C1-C6 alkyl;
- R3 together with R4 and X forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R3 is absent;
- R7 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R7 and R4 together form a double bond;
- R8 is H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- R8 together with R9 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms, or R8 is absent;
- R9 is H or C1-C6 alkyl;
- R9 together with R8 and Y forms an optionally substituted 5-6 membered heterocycle containing 1-2 nitrogen, oxygen or sulfur atoms;
- R9 and R11 together form a double bond;
- R10 is absent, H, C(O)—C1-C6 alkyl, C1-C6 alkyl;
- or R10 and R11 together form a double bond;
- R11 is H or C1-C6 alkyl;
- or R11 and R19 together form a double bond;
- R11 and R9 together form a double bond;
- R12, R13, R14, R15, R16 and R17 are independently H, C(O)—C1-C6 alkyl or C1-C6 alkyl;
- and the dotted line indicates the presence of either a single or a double bond wherein the valences of a single bond are completed by hydrogens.
The method of claim 32, wherein said animal is a human.
The method of claim 32-33, wherein said injury or disease is severe or moderate TBI.
Dependencies are inferred from the claim text.