Small molecule ras inhibitors
AssigneeOhio State Innovation Foundation
InventorsRoger BRIESEWITZ, Dehua PEI, Punit UPADHYAYA
Life of this patent
Estimating the term…
Abstract
Disclosed herein are novel compounds that are Ras inhibitors. Also disclosed are compositions comprising the compounds and methods of using the compounds in treating various diseases. In another aspect, provided is an antibody-drug-conjugate comprising an antibody conjugated with a compound described herein. In still another aspect, provided is a pharmaceutical composition comprising a compound or antibody-drug-conjugate described herein. In a further aspect, provided is method of treating a cancer comprising administering a therapeutically effective amount of a compound or antibody-drug-conjugate described herein to a patient in need thereof.
Claims29
A compound of formula A
- or a tautomer, a pharmaceutically acceptable salt and/or a solvate thereof;
- wherein
- R1, R2, R4, R6, R7, R8, R10, R11 and each R15 are independently H, C1-C6 alkyl, substituted C1-C6 alkyl, phenyl, or substituted phenyl, wherein at least two of R1, R2, R4, R6, R7, R8, R10, R11 and R15 are C1-C6 alkyl substituted with NHC(═NH)NH2 and no four consecutive R1, R2, R4, R6, R7, R8, R10, R11 and R15 are (CH2)3NHC(═NH)NH2;
- R3 and R5 are independently L-R, wherein L is covalent bond, C1-C6 alkylene, (CH2)sC(O)NH or (CH2)sNHC(O), and R is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R9 is C1-C6 alkyl or C1-C6 alkyl substituted with OH;
- R1′, R2′, R3′, R4′, R5′, R6′, R7′, R8′, R9′, R10′, R11′ and each R15′ are independently H or methyl;
- x is 0, 1, 2, 3 or 4;
- s is 0, 1, 2, or 3;
- m is 0 or 1;
- and
- n is 0 or 1.
A compound of formula I, II or III
- or a tautomer, a pharmaceutically acceptable salt and/or a solvate thereof;
- wherein
- R1, R2, R4, R6, R7, R8, R10 and R11 are independently H, C1-C6 alkyl, substituted C1-C6 alkyl, phenyl, or substituted phenyl, wherein at least two of R1, R2, R4, R6, R7, R8, R10 and R11 are C1-C6 alkyl substituted with NHC(═NH)NH2 and R1, R2, R10, and R11 cannot be all (CH2)3NHC(═NH)NH2;
- R3 and R5 are independently L-R, wherein L is covalent bond, C1-C6 alkylene, (CH2)sC(O)NH or (CH2)sNHC(O), and R is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R9 is C1-C6 alkyl or C1-C6 alkyl substituted with OH;
- R1′, R2′, R3′, R4′, R5′, R6′, R7′, R8′, R9′, R10′ and R11′ are independently H or methyl;
- s is 0, 1, 2, or 3;
- m is 0 or 1;
- and
- n is 0 or 1.
A compound of formula IB, IIB, IIIB, IVB, VB or VIB:
- or a tautomer, a pharmaceutically acceptable salt and/or a solvate thereof;
- wherein
- R1, R2, R4, R6, R7, R8, R10 and R11 are independently H, C1-C6 alkyl, substituted C1-C6 alkyl,
- phenyl, or substituted phenyl, wherein at least two of R1, R2, R4, R6, R7, R8, R10 and R11 are C1-C6 alkyl substituted with NHC(═NH)NH2 and R1, R2, R10 and R11 cannot be all (CH2)3NHC(═NH)NH2;
- R3 and R5 are independently L-R, wherein L is covalent bond, C1-C6 alkylene, (CH2)sC(O)NH or (CH2)sNHC(O), and R is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- R9 is C1-C6 alkyl or C1-C6 alkyl substituted with OH;
- R8 is hydrogen or methyl;
- s is 0, 1, 2, or 3;
- m is 0 or 1;
- and
- n is 0 or 1.
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Dependencies are inferred from the claim text.