# US 11,078,160 B2 · Ethynyl compounds, their preparation and their therapeutic use for the treatment of malaria > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,078,160 B2 - Document ID: US11078160B2 - Status: Granted - Kind: B2 - Application number: 16/628,720 - Filed: 2018-07-04 - Published: 2020-09-10 - Granted: 2021-08-03 - Earliest claimed: 2017-07-04 - Assignees: Sanofi - Applicants: Sanofi - Inventors: Cécile Pascal; Alain Pellet; Gilles Courtemanche; Simon Campbell - Web page: https://patentgrep.com/patent/US11078160B2 ## CPC - C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates - A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol - A61K 31/4402: only substituted in position 2, e.g. pheniramine, bisacodyl - A61P 33/06: Antimalarials - C07C 279/22: Y being a hydrogen or a carbon atom, e.g. benzoylguanidines - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The present disclosure relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof wherein R1 means a fluorine atom or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms; R2 means a chlorine atom, a linear alkyl radical containing 1, 2 or 3 carbon atoms or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms, and R means a hydrogen atom or a radical of formula (Ia). The present disclosure also relates to processes for their preparation as well their therapeutic uses, in particular such as for use in the treatment of malaria. ## Claims ### Claim 1 A compound of formula (I): wherein: R1 is a fluorine atom or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms, R2 is a chlorine atom; a linear alkyl radical containing 1, 2 or 3 carbon atoms optionally substituted with at least one fluorine atom; or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms, and R is a hydrogen atom or a radical of formula (Ia) R3 is a hydrogen atom; a hydroxyl radical; or a linear or branched alkyl radical containing 1, 2 or 3 carbon atoms, and R3 is in position 5 or in position 6 of said radical of formula (Ia), or a pharmaceutically acceptable salt thereof. ### Claim 2 (depends on 1) The compound according to claim 1, wherein R1 is a fluorine atom or a trifluoromethyl radical. ### Claim 3 (depends on 1) The compound according to claim 1, wherein R2 is a chlorine atom, a methyl radical or a perhalogeno linear alkyl radical containing 1, 2 or 3 carbon atoms. ### Claim 4 (depends on 1) The compound according to claim 1, wherein R is the radical of formula (Ia). ### Claim 5 (depends on 1) The compound according to claim 1, wherein R is a radical of formula (Ia) and R3 is in position 5 or 6 of said radical of formula (Ia). ### Claim 6 (depends on 1) The compound according to claim 1, wherein R is the radical of formula (Ia) and R3 is a hydrogen atom, a hydroxyl radical or a methyl radical. ### Claim 7 (depends on 5) The compound according to claim 5, wherein R is the radical of formula (Ia) and R3 is a hydroxyl radical in position 5 of said radical of formula (Ia). ### Claim 8 (depends on 5) The compound according to claim 5, wherein R is the radical of formula (Ia) and R3 is a linear or branched alkyl radical containing 1, 2 or 3 carbon atoms in position 6 of said radical of formula (Ia). ### Claim 9 (depends on 1) The compound according to claim 1, wherein at least one of R1 and R2 is a perfluoromethyl radical. ### Claim 10 (depends on 1) The compound according to claim 1, wherein both R1 and R2 are a perfluoromethyl radical. ### Claim 11 (depends on 1) The compound according to claim 1, said compound being selected from: 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide, 5-((3-((diaminomethylene)carbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-2-methyl-N-(6-methylpyridin-2-yl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-fluorophenyl)ethynyl)-N-(6-methylpyridin-2-yl)-2-(trifluoromethyl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-trifluoromethyl)phenyl)ethynyl)-2-methyl-N-(pyridin-2-yl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(5-hydroxypyridin-2-yl)-2-(trifluoromethyl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-2-chloro-N-(pyridin-2-yl)benzamide, 5-((3-(carbamimidoylcarbamoyl)-5-fluorophenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide, N-carbamimidoyl-3-((3-carbamoyl-4-(trifluoromethyl)phenyl)ethynyl)-5-trifluoromethyl)benzamide, and their pharmaceutically acceptable salts. ### Claim 12 (depends on 1) The compound according to claim 1, said compound being selected from: 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide malonic acid, 5-((3-((diaminomethylene)carbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-2-methyl-N-(6-methylpyridin-2-yl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-fluorophenyl)ethynyl)-N-(6-methylpyridin-2-yl)-2-(trifluoromethyl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-trifluoromethyl)phenyl)ethynyl)-2-methyl-N-(pyridin-2-yl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-N-(5-hydroxypyridin-2-yl)-2-(trifluoromethyl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-(trifluoromethyl)phenyl)ethynyl)-2-chloro-N-(pyridin-2-yl)benzamide hydrochloride, 5-((3-(carbamimidoylcarbamoyl)-5-fluorophenyl)ethynyl)-N-(pyridin-2-yl)-2-(trifluoromethyl)benzamide hydrochloride, and pharmaceutically acceptable salts thereof. ### Claim 13 (depends on 1) A composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt thereof and of at least one other anti-malaria active principle different from said at least one compound. ### Claim 14 (depends on 1) A pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, diluent or excipient thereof. ### Claim 15 (depends on 1) A method of treating malaria in a patient in need thereof that comprises administering of a compound according to claim 1 or a pharmaceutically acceptable salt thereof or a composition comprising said compound or pharmaceutically active salt to a patient having malaria.