# US 2021/0276972 A1 · Quinazoline Derivatives as VEGF Inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0276972 A1 - Document ID: US20210276972A1 - Status: Published application - Kind: A1 - Application number: 17/150,856 - Filed: 2021-01-15 - Published: 2021-09-09 - Earliest claimed: 1999-11-05 - Assignees: Genzyme Corporation - Applicants: Genzyme Corporation - Inventors: Andrew Peter Thomas; Elaine Sophie Elizabeth Stokes; Laurent Francois Andre Hennequin - Web page: https://patentgrep.com/patent/US20210276972A1 ## CPC - C07D 401/12: linked by a chain containing hetero atoms as chain links - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 17/06: Antipsoriatics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 27/02: Ophthalmic agents - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61P 37/00: Drugs for immunological or allergic disorders - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention relates to quinazoline derivatives of formula (I), wherein in is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5akylR3 (wherein R3 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis. ## Claims ### Claim at position 1 1-13. (canceled) ### Claim 14 A pharmaceutical composition comprising 100 mg to 300 mg of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. ### Claim 15 (depends on 14) The pharmaceutical composition according to claim 14, wherein the pharmaceutical composition is formulated for oral administration. ### Claim 16 (depends on 15) The pharmaceutical composition according to claim 15, in the form of a tablet. ### Claim 17 (depends on 16) The pharmaceutical composition according to claim 16, wherein the tablet is coated. ### Claim 18 (depends on 17) The pharmaceutical composition according to claim 17, wherein the coating is an enteric coating. ### Claim 19 (depends on 14) The pharmaceutical composition according to claim 14, wherein the amount of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline is 100 mg. ### Claim 20 (depends on 14) The pharmaceutical composition according to claim 14, wherein the amount of the pharmaceutically acceptable salt of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline is 100 mg. ### Claim 21 (depends on 14) The pharmaceutical composition according to claim 14, wherein the amount of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline is 300 mg. ### Claim 22 (depends on 14) The pharmaceutical composition according to claim 14, wherein the amount of the pharmaceutically acceptable salt of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline is 300 mg. ### Claim 23 (depends on 14) The pharmaceutical composition according to claim 14, wherein the at least one pharmaceutically acceptable excipient is selected from the group consisting of lactose, croscarmellose sodium, maize starch, polyvinylpyrollidone and magnesium stearate. ### Claim 24 (depends on 14) The pharmaceutical composition according to claim 14, comprising 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline. ### Claim 25 (depends on 14) The pharmaceutical composition according to claim 14, comprising a pharmaceutically acceptable salt of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline. ### Claim 26 A pharmaceutical composition comprising 100 mg of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is formulated as a tablet. ### Claim 27 A pharmaceutical composition comprising 300 mg of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition is formulated as a tablet.