Guanidine compounds and use thereof
AssigneeImmunoMet Therapeutics Inc.
InventorsSung Wuk Kim, Hong Woo Kim, Sang Hee Yoo, Ji Sun Lee, Hye Jin Heo, Hong Bum Lee, Ji Ae Kook, Young Woo Lee, Mi Jeong Kim, Woong Cho
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Abstract
The present invention relates to guanidine compounds for inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and use thereof. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating a OXPHOS-related disease, particularly cancer, by inhibiting mitochondrial oxidative phosphorylation and reprogramming cellular metabolism.
Claims6
A compound of chemical formula 1, or a pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate thereof;
- wherein:
- wherein R1 is H,
- R2, R3 and R4 are H;
- A is —C(NH)—NH—;
- R5 is —(CH2)n- where n is an integer from 1 to 6,
- R6 is C8-C9 cycloalkyl, or 7 or 9-11-membered benzocycloalkyl, where cycloalkyl, and benzocycloalkyl may be substituted with at least one of hydroxyl, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C3-C7 cycloalkyl, C6-C9 arylalkyl, SO2NH2, OR8, or NR10R11, where each of R8, R10 and R11 is, independently, hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, or C6-C12 aryl;
- or
- R6 is C10 cycloalkyl, or 7-membered heterocycloalkyl, where C10 cycloalkyl and 7-membered heterocycloalkyl are substituted with at least one of hydroxyl, halogen, C1-C4alkyl, C1-C4 haloalkyl, C3-C7 cycloalkyl, C6-C9 arylalkyl, SO2NH2, OR8, or NR10R11, where each of R8, R10, and R11 is, independently, hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, or C6-C12 aryl.
A compound of chemical formula 3, or a pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate thereof:
- wherein R1 is H,
- R2, R3, and R4 are H,
- n is an integer from 1 to 6, and
- an adjacent pair of R12, R13, R14, R15, or R16 are C1-C4 alkyl groups that, together with the atoms to which they are attached, combine with each other to form a 4 to 7 membered saturated or unsaturated cycloalkyl group;
- and
- the variables R12, R13, R14, R15, and R16 that are not part of the adjacent pair that combine with each other to form a 4 to 7 membered saturated or unsaturated cycloalkyl group are hydrogen.
A compound selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:
- N-1-(3,4-dichloro)phenethylbiguanide,
- N-1-(2,5-dichloro)phenethylbiguanide,
- N-1-(2-chloro)phenethylbiguanide,
- N-1-(3-methoxy)phenethylbiguanide,
- N-1-(2-(5,6,7,8-tetrahydronaphthalen-1-yl)ethyl)biguanide,
- N-1-(2-(5,6,7,8-tetrahydronaphthalen-2-yl)ethyl)biguanide,
- N-1-(2-(5,6,7,8-tetrahydronaphthalen-2-yl)methyl)biguanide, and
- N-1-(2-(2,3-dihydro-1H-inden-5-yl)ethyl)biguanide.
A compound selected from the group consisting of:
- N-1-(2-(2,3-dihydro-1H-inden-5-yl)ethyl)biguanide,
- N-1-(2-(5,6,7,8-tetrahydronaphthalen-2-yl)ethyl)biguanide, and
- N-1-(2-(5,6,7,8-tetrahydronaphthalen-2-yl)methyl)biguanide, or
- a pharmaceutically acceptable salt thereof.
A compound selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:
- 1-(4-trifluoromethoxyphenethyl)guanide, and
- 1-(1-(5,6,7,8-tetrahydronaphthalen-1-yl)ethyl)guanide.
Dependencies are inferred from the claim text.