# US 2014/0194486 A1 · Therapeutic agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0194486 A1 - Document ID: US20140194486A1 - Status: Published application - Kind: A1 - Application number: 14/085,632 - Filed: 2013-11-20 - Published: 2014-07-10 - Earliest claimed: 2008-06-25 - Assignees: Cancer Research Technology Limited - Applicants: Cancer Research Technology Limited - Inventors: Bernard Thomas GOLDING; Christiane Riedinger; Roger John Griffin; Ian Robert Hardcastle; Eric Valeur; Anna Frances Watson; Martin Noble - Web page: https://patentgrep.com/patent/US20140194486A1 ## CPC - C07D 209/49: and having in the molecule an acyl radical containing a saturated three-membered ring, e.g. chrysanthemumic acid esters - A61K 31/4035: Isoindoles, e.g. phthalimide - A61K 31/4402: only substituted in position 2, e.g. pheniramine, bisacodyl - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 209/48: with oxygen atoms in positions 1 and 3, e.g. phthalimide - C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms - C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms - 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 ## Abstract A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53. ## Claims ### Claim at position 1 1-40. (canceled) ### Claim 41 A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein in formulae I: X is O; R1 is selected from substituted or unsubstituted aralkyl, substituted alkyl, propyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heteroaralkyl; R2 is selected from substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted branched hydroxyalkyl, substituted or unsubstituted cycloalkyl having 6 ring carbon atoms or greater, substituted or unsubstituted cycloalkenyl, hydroxyalkylaralkyl, hydroxyalkylheteroaralkyl, and a carboxylic acid-containing group; R3 is selected from substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylamine, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, and substituted or unsubstituted heteroaralkyl; and R4-R7 represents groups R4, R5, R6 and R7 which are independently selected from hydrogen, halo, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted alkylamine, substituted or unsubstituted alkoxy, trifluoromethyl, amino, nitro, carboxyl, carbonyl, methylsulfone, trifluoromethylsulfone, cyano and substituted or unsubstituted sulfonamide. ### Claim 42 (depends on 41) A compound according to claim 41, wherein R1 is selected from substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and/or R2 is selected from acetyl, hydroxyalkenyl, hydroxyalkynyl, branched 5-carbon hydroxyalkyl, hydroxycycloalkyl, hydroxycycloalkenyl, hydroxymethylcycloalkyl, hydroxymethylcycloalkylmethylene, and hydroxyl alkylbenzyl; and/or R3 is selected from substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl. ### Claim 43 (depends on 41) A compound according to claim 41, wherein R2 is selected from hydroxypropyl, hydroxybutyl, hydroxybutenyl, hydroxycyclopentenyl, hydroxycyclohexenyl and n-propylamine. ### Claim 44 (depends on 41) A compound according to claim 41, wherein R1 is substituted benzyl. ### Claim 45 (depends on 41) A compound according to claim 41, wherein R1 is 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, cyanobenzyl, or 4-iodobenzyl. ### Claim 46 (depends on 41) A compound according to claim 41, wherein R3 is substituted or unsubstituted phenyl. ### Claim 47 (depends on 41) A compound according to claim 41, wherein R3 is 4-chlorophenyl or 4-fluorophenyl. ### Claim 48 (depends on 41) A compound according to claim 41, wherein at least one of R4-R1 is a chlorine atom. ### Claim 49 (depends on 41) A compound according to claim 41, or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from substituted aryl, substituted heteroaryl, substituted aralkyl, and substituted heteroaralkyl. ### Claim 50 (depends on 41) A compound according to claim 41, wherein R1 is substituted aralkyl, R2 is acyclic hydroxyalkyl, and R3 is substituted aryl. ### Claim 51 (depends on 41) A compound according to claim 41, wherein the R1 group is the S-enantiomer. ### Claim 52 (depends on 41) A pharmaceutical composition comprising an effective amount of at least one compound according to claim 41, and a pharmaceutically acceptable carrier. ### Claim 53 (depends on 41) A method of treating cancer in a mammal comprising administering a therapeutically effective amount of a medicament comprising at least one compound according to claim 41. ### Claim 54 (depends on 53) A method according to claim 53, wherein the cancer overexpresses MDM2. ### Claim 55 (depends on 53) A method according to claim 53, wherein the cancer is selected from osteosarcoma, colorectal carcinoma, neuroblastoma and uterus chorion cancer. ### Claim 56 (depends on 41) A method of inhibiting the interaction of MDM2 protein with p53 comprising administering a therapeutically effective amount of a compound according to claim 41 or a pharmaceutically acceptable salt thereof. ### Claim 57 (depends on 53) A method according to claim 53 further comprising administering a therapeutically effective amount of at least one additional anticancer agent. ### Claim 58 (depends on 54) A method according to claim 54 further comprising administering a therapeutically effective amount of at least one additional anticancer agent. ### Claim 59 (depends on 41) A kit comprising at least one compound according to claim 41; and instructions for use. ### Claim 60 (depends on 41) A method of manufacturing a medicament comprising, combining a compound according to claim 41 or a pharmaceutically acceptable salt thereof, with a carrier that comprises one or more accessory ingredients.