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
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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.
Claims5
A compound having Chemical Formula 1, or a pharmaceutically acceptable salt thereof:
- wherein
- R1 and R2 are taken together with N to which they are attached to form a pyrrolidine group and is substituted with at least a group selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C2 alkylamino,
- R3 and R4 are H,
- n is 0, 1 or 2, and
- R5 is an aryl group represented by Chemical Formula 2,
- wherein R6, R7, R8, R9, and R10 are independently SR11 where R11 is C1-C3 alkyl, C1-C3 haloalkyl, or C6-C10 aryl, wherein only one of R6, R7, R8, R9, and R10 is SR11 with the other positions being H or OR12, where R12 is a is C1-C3 alkyl, C6-C10 aryl, wherein up to three of R6, R7, R8, R9, and R10 are OR12 with the other positions being H.
A compound selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:
- N—(N-(4-(trifluoromethoxy)phenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(4-phenoxyphenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3-phenoxyphenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(4-(trifluoromethyl)phenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3-chloro-4-iodophenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(4-(trifluoromethylthio)phenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(2-chlorophenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(2-bromophenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(2,4-dichlorophenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(2-propylphenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3,4-dimethoxyphenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3-chloro-4-(trifluoromethoxy)phenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3-bromo-4-(trifluoromethoxy)phenyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(4-(trifluoromethyl)benzyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3-(trifluoromethyl)benzyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(3,4-(dichloro)benzyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-phenethylcarbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(4-bromophenethyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(cyclopropylmethyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(cyclopropyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide,
- N—(N-(cyclohexyl)carbamimidoyl)-3,3-difluoropyrrolidine-1-carboximidamide, and
- N—(N-(4-(trifluoromethoxy)phenyl)carbamimidoyl)-(R)-3-fluoropyrrolidine-1-carboximidamide.
Dependencies are inferred from the claim text.