Patent EA-002836-B1 (EA)
Title: N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolamine mesylate anhydrate and monohydrate
Inventor: ALLEN DOUGLAS JOHN MELDRUM
IPC: A61K31/505
Filed: 1999-04-08
Abstract: 1. A compound N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate or a hydrate form thereof. 2. A compound according to Claim 1 wherein said compound is an anhydrous form of  N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate. 3. A compound according to Claim 2 wherein said compound is polymorph A characterized by the following peaks in its X-ray powder diffraction pattern Peak No. 1 2 3 4 5 6 7 8 9 10 2q ( degree ) Cu 6,3 7,15 9,8 13,4 13,7 18,05 18,9 19,6 20,0 21,35 d space 14,1 12,3 9,0 6,6 6,4 4,9 4,7 4,5 4,4 4,15 Peak No. 11 12 13 14 15 16 17 18 19 20 2q ( degree ) Cu 21,8 23,1 26,8        d space 4,1 3,85 3,3          4. A compound according to Claim 2 wherein said compound is polymorph B characterized by the following peaks in its X-ray powder diffraction pattern Peak No. 1 2 3 4 5 6 7 8 9 10 2q ( degree ) Cu 5,4 8,8 13,4 13,7 15,3 15,7 17,4 17,8 18,4 18,8 d space 16,3 10,1 6,6 6,5 5,8 5,65 5,1 5,0 4,8 4,7 Peak No. 11 12 13 14 15 16 17 18 19 20 2q ( degree ) Cu 19,5 19,85 20,1 21,1 21,8 22,6 24,1 25,2 25,9 26,7 d space 4,55 4,5 4,4 4,2 4,1 3,9 3,7 3,5 3,4 3,3 Peak No. 21 22 23 24 25 26 27 28 29 30 2q ( degree ) Cu 28,3 30,9         d space 3,1 2,9           5. A compound according to Claim 2 wherein said compound is polymorph C characterized by the following peaks in its X-ray powder diffraction pattern Peak No. 1 2 3 4 5 6 7 8 9 10 2q ( degree ) Cu 6,0 8,3 10,3 11,5 12,55 13,45 16,0 16,75 17,4 17,9 d space 14,7 10,6 8,6 7,7 7,05 6,6 5,5 5,3 5,1 4,95 Peak No. 11 12 13 14 15 16 17 18 19 20 2q ( degree ) Cu 18,1 18,65 19,35 20,6 23,0 24,0 24,8 26,75 27,2 36,3 d space 4,9 4,75 4,6 4,3 3,9 3,7 3,6 3,3 3,3 2,5   6. A compound according to Claim 1 wherein said compound is N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate monohydrate. 7. A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal which comprises a therapeutically effective amount of a compound according to Claim 1 and a pharmaceutically acceptable carrier. 8. The pharmaceutical composition of Claim 7 wherein said hyperproliferative disorder is a cancer selected from brain, lung, squamous cell, bladder, gastric, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, oesophageal, gynecological and thyroid cancer. 9. A method of treating a hyperproliferative disorder in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound according to Claim 1. 10. The method of Claim 9 wherein said method is for the treatment of a cancer selected from brain, squamous cell, bladder, gastric, pancreatic, breast, head, neck, oesophageal, prostate, colorectal, lung, renal, kidney, ovarian, gynecological and thyroid cancer. 11. A method for the treatment of a hyperproliferative disorder in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound according to Claim 1 in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, anti-hormones, and anti-androgens.