Claims for Patent: 8,835,443

Summary for Patent: 8,835,443

Title:	Pyrimidine compound and medical use thereof
Abstract:	The present invention relates to a pyrimidine compound or a pharmaceutically acceptable salt thereof represented by the following formula [I] wherein each symbol is as defined in the specification and a method of therapeutically or prophylactically treating an undesirable cell proliferation, comprising administering such a compound. The compound of the present invention has superior activity in suppressing undesirable cell proliferation, particularly, an antitumor activity, and is useful as an antitumor agent for the prophylaxis or treatment of cancer, rheumatism, and the like. In addition, the compound of the present invention can be a more effective antitumor agent when used in combination with other antitumor agents such as an alkylating agent or metabolism antagonist.
Inventor(s):	Hisashi Kawasaki, Hiroyuki Abe, Kazuhide Hayakawa, Tetsuya Iida, Shinichi Kikuchi, Takayuki Yamaguchi, Toyomichi Nanayama, Hironori Kurachi, Masahiro Tamaru, Yoshikazu Hori, Mitsuru Takahashi, Takayuki Yoshida, Toshiyuki Sakai
Assignee:	Japan Tobacco Inc
Application Number:	US12/626,443
Patent Claims:	1. A method of therapeutically treating an undesirable cell proliferation in a mammal in need thereof comprising administering to the mammal a therapeutic amount of a compound represented by the following formula [I] or a pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein X1 and X2 are the same or different and each is a carbon atom or a nitrogen atom, a moiety is R1 and R2 are the same or different and each is a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, or wherein m is 0 or an integer of 1 to 4, ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R6 is wherein m is 0, and ring Cy is a C3-12 carbon ring group ora heterocyclic group, wherein the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R3, R4, and R5 are the same or different and each is a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, or R2 and R3 are optionally linked to form a C1-4 alkylene group, or R4 and R5 are optionally linked to form a C1-4 alkylene group, wherein group A is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-4 alkyl group, 5) —ORA1 wherein RA1 is a hydrogen atom or a C1-4 alkyl group, 6) —SRA2 wherein RA2 is a hydrogen atom or a C1-4 alkyl group, 7) —NRA3RA4 wherein RA3 and RA4 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 8) —COORA5 wherein RA5 is a hydrogen atom or a C1-4 alkyl group, 9) —NRA6 CORA7 wherein RA6 is a hydrogen atom or a C1-4 alkyl group, RA7 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 10) —NRA8COORA9 wherein RA8 and RA9 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 11) a C3-12 carbon ring group and 12) a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, each of the C1-4 alkyl groups of the above-mentioned 4), RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8 and RA9 is optionally substituted by the same or different 1 to 3 substituents selected from the following group C, and each of the C3-12 carbon ring groups of the above-mentioned 11) and RA7, and the heterocyclic groups of 12) and RA7 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C group B is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-8 alkyl group, 5) a C2-4 alkenyl group, 6) a C2-4 alkynyl group, 7) —ORB1 wherein RB1 is a hydrogen atom or a C1-4 alkyl group, 8) —SRB2 wherein RB2 is a hydrogen atom or a C1-4 alkyl group, 9) —NRB3RB4 wherein RB3 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, and RB4 is a hydrogen atom or a C1-4 alkyl group, 10) —NRB5CORB6 wherein RB5 is a hydrogen atom or a C1-4 alkyl group, and RB6 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 11) —NRB7COORB8 wherein RB7 and RB8 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 12) —NRB9CONRB10RB11 wherein RB9, RB10 and RB11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 13) —NRB12CONRB13ORB14 wherein RB12, RB13 and RB14 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 14) —NRB15SO2RB16 wherein RB15 is a hydrogen atom or a C1-4 alkyl group, and RB16 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 15) —SO2—RB17 wherein RB17 is a C1-4 alkyl group or a heterocyclic group, 16) —SO2NRB18RB19 wherein RB18 and RB19 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 17) —P(═O)(RB20)(RB21) wherein RB20 and RB21 are the same or different and each is a C1-4 alkyl group, 18) —COORB22 wherein RB22 is a hydrogen atom or a C1-4 alkyl group, 19) —CONRB23RB24 wherein RB23 and RB24 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 20) —NRB25SO2NRB26RB27 wherein RB25, RB26 and RB27 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 21) —NRB28SO2NRB29CONRB30RB31 wherein RB28, RB29, RB30 and RB31 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 22) a C3-12 carbon ring group and 23) a heterocyclic group wherein each of the “C1-8 alkyl group” of the above-mentioned 4), and the C1-4 alkyl groups for Rb1 to RB31 is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, each of the C2-4 alkenyl group of 5) and the C2-4 alkynyl group of 6) is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and each of the C3-12 carbon ring group of the above-mentioned 22), RB3, RB6 and RB16, and the heterocyclic group of the above-mentioned 23), RB3, RB6, RB16 and RB17 optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and group C is a group consisting of 1) a halogen atom, 2) a cyano group, 3) a C1-4 alkyl group, 4) —ORC1 wherein RC1 is a hydrogen atom or a C1-4 alkyl group, 5) —NRC2RC3 wherein RC2 and RC3 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 6) —COORC4 wherein RC4 is a hydrogen atom or a C1-4 alkyl group and 7) an oxo group, whereupon the undesirable cell proliferation is treated. 2. The method of claim 1, wherein the compound is represented by the following formula [I-1]: wherein each symbol in the formula is as defined in claim 1. 3. The method of claim 1, wherein the compound is represented by the following formula [I-2]: wherein each symbol in the formula is as defined in claim 1. 4. The method of claim 1, wherein the compound is represented by the following formula [I-3]: wherein each symbol in the formula is as defined in claim 1. 5. The method of claim 1, wherein R1 is a C1-6 alkyl group. 6. The method of claim 1, wherein R1 is wherein m is 0, and ring Cy is a C3-12 carbon ring group, wherein the C3-12 carbon ring group is optionally substituted by 1 to 5 substituents selected from group B of claim 1. 7. The method of claim 1, wherein R1 is a C3-8 cycloalkyl group. 8. The method of claim 7, wherein R1 is a cyclopropyl group. 9. The method of claim 1, wherein R2 is wherein m is 0, and ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from group B of claim 1. 10. The method of claim 1, wherein R3 is a C1-6 alkyl group. 11. The method of claim 1, wherein R4 is a hydrogen atom. 12. The method of claim 1, wherein R5 is a hydrogen atom. 13. The method of claim 1, wherein the undesirable cell proliferation causes rheumatism. 14. The method of claim 1, wherein the undesirable cell proliferation causes a tumor. 15. A method of inhibiting MEK in a mammal in need thereof comprising administering to the mammal an MEK inhibiting amount of a compound represented by the following formula [I] or a pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein X1 and X2 are the same or different and each is a carbon atom or a nitrogen atom, a moiety is R1 and R2 are the same or different and each is a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, or wherein m is 0 or an integer of 1 to 4, ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R6 is wherein m is 0, and ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R3, R4, and R5 are the same or different and each is a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, or R2 and R3 are optionally linked to form a C1-4 alkylene group, or R4 and R5 are optionally linked to form a C1-4 alkylene group, wherein group A is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-4 alkyl group, 5) —ORA1 wherein RA1 is a hydrogen atom or a C1-4 alkyl group, 6) —SRA2 wherein RA2 is a hydrogen atom or a C1-4 alkyl group, 7) —NRA3RA4 wherein RA3 and RA4 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 8) —COORA5 wherein RA5 is a hydrogen atom or a C1-4 alkyl group, 9) —NRA6CORA7 wherein RA6 is a hydrogen atom or a C1-4 alkyl group, RA7 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 10) —NRA8COORA9 wherein RA8 and RA9 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 11) a C3-12 carbon ring group and 12) a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, each of the C1-4 alkyl groups of the above-mentioned 4), RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8 and RA9 is optionally substituted by the same or different 1 to 3 substituents selected from the following group C, and each of the C3-12 carbon ring groups of the above-mentioned 11) and RA7, and the heterocyclic groups of 12) and RA7 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C group B is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-8 alkyl group, 5) a C2-4 alkenyl group, 6) a C2-4 alkynyl group, 7) —ORB1 wherein RB1 is a hydrogen atom or a C1-4 alkyl group, 8) —SRB2 wherein RB2 is a hydrogen atom or a C1-4 alkyl group, 9) —NRB3RB4 wherein RB3 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, and RB4 is a hydrogen atom or a C1-4 alkyl group, 10) —NRB5CORB6 wherein RB5 is a hydrogen atom or a C1-4 alkyl group, and RB6 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 11) —NRB7COORB8 wherein RB7 and RB8 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 12) —NRB9CONRB10RRB11 wherein RB9, RB10 and RB11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 13) —NRB12CONRB13ORB14 wherein RB12, RB13 and RB14 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 14) —NRB15SO2RB16 wherein RB15 is a hydrogen atom or a C1-4 alkyl group, and RB16 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 15) —SO2—RB17 wherein RB17 is a C1-4 alkyl group or a heterocyclic group, 16) —SO2NRB18RB19 wherein RB18 and RB19 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 17) —P(═O)(RB20)(RB21) wherein RB20 and RB21 are the same or different and each is a C1-4 alkyl group, 18) —COORB22 wherein RB22 is a hydrogen atom or a C1-4 alkyl group, 19) —CONRB23RB24 wherein RB23 and RB24 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 20) —NRB25SO2NRB26RB27 wherein RB25, RB26 and RB27 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 21) —NRB28SO2NRB29CONRB30RB31 wherein RB28, RB29, RB30 and RB31 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 22) a C3-12 carbon ring group and 23) a heterocyclic group wherein each of the “C1-8 alkyl group” of the above-mentioned 4), and the C1-4 alkyl groups for RB1 to RB31 is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, each of the C2-4 alkenyl group of 5) and the C2-4 alkynyl group of 6) is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and each of the C3-12 carbon ring group of the above-mentioned 22), RB3, RB6 and RB16, and the heterocyclic group of the above-mentioned 23), RB3, RB6, RB16 and RB17 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and group C is a group consisting of 1) a halogen atom, 2) a cyano group, 3) a C1-4 alkyl group, 4) —ORC1 wherein RC1 is a hydrogen atom or a C1-4 alkyl group, 5) —NRC2RC3 wherein RC2 and RC3 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 6) —COORC4 wherein RC4 is a hydrogen atom or a C1-4 alkyl group and 7) an oxo group, whereupon MEK is inhibited. 16. A method of inducing p15 protein in a mammal in need thereof comprising administering to the mammal a p15 protein inducing amount of a compound represented by the following formula [I] or a pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein X1 and X2 are the same or different and each is a carbon atom or a nitrogen atom, a moiety is R1 and R2 are the same or different and each is a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, or wherein m is 0 or an integer of 1 to 4, ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R6 is wherein m is 0, and ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R3, R4, and R5 are the same or different and each is a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, or R2 and R3 are optionally linked to form a C1-4 alkylene group, or R4 and R5 are optionally linked to form a C1-4 alkylene group, wherein group A is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-4 alkyl group, 5) —ORA1 wherein RA1 is a hydrogen atom or a C1-4 alkyl group, 6) —SRA2 wherein RA2 is a hydrogen atom or a C1-4 alkyl group, 7) —NRA3RA4 wherein RA3 and RA4 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 8) —COORA5 wherein RA5 is a hydrogen atom or a C1-4 alkyl group, 9) —NRA6CORA7 wherein RA6 is a hydrogen atom or a C1-4 alkyl group, RA7 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 10) —NRA8COORA9 wherein RA8 and RA9 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 11) a C3-12 carbon ring group and 12) a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, each of the C1-4 alkyl groups of the above-mentioned 4), RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8 and RA9 is optionally substituted by the same or different 1 to 3 substituents selected from the following group C, and each of the C3-12 carbon ring groups of the above-mentioned 11) and RA7, and the heterocyclic groups of 12) and RA7 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C group B is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-8 alkyl group, 5) a C2-4 alkenyl group, 6) a C2-4 alkynyl group, 7) —ORB1 wherein RB1 is a hydrogen atom or a C1-4 alkyl group, 8) —SRB2 wherein RB2 is a hydrogen atom or a C1-4 alkyl group, 9) —NRB3RB4 wherein RB3 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, and RB4 is a hydrogen atom or a C1-4 alkyl group, 10) —NRB5CORB6 wherein RB5 is a hydrogen atom or a C1-4 alkyl group, and RB6 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 11) —NRB7COORB8 wherein RB7 and RB8 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 12) —NRB9CONRB10RB11 wherein RB9, RB10 and RB11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 13) —NRB12CONRB13ORB14 wherein RB12, RB13 and RB14 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 14) —NRB15SO2RB16 wherein RB15 is a hydrogen atom or a C1-4 alkyl group, and RB16 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 15) —SO2—RB17 wherein RB17 is a C1-4 alkyl group or a heterocyclic group, 16) —SO2NRB18RB19 wherein RB18 and RB19 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 17) —P(═O)(RB20)(RB21) wherein RB20 and RB21 are the same or different and each is a C1-4 alkyl group, 18) —COORB22 wherein RB22 is a hydrogen atom or a C1-4 alkyl group, 19) —CONRB23RB24 wherein RB23 and RB24 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 20) —NRB25SO2NRB26RB27 wherein RB25, RB26 and RB27 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 21) —NRB28SO2NRB29CONRB30RB31 wherein RB28, RB29, RB30 and RB31 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 22) a C3-12 carbon ring group and 23) a heterocyclic group wherein each of the “C1-8 alkyl group” of the above-mentioned 4), and the C1-4 alkyl groups for RB1 to RB31 is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, each of the C2-4 alkenyl group of 5) and the C2-4 alkynyl group of 6) is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and each of the C3-12 carbon ring group of the above-mentioned 22), RB3, RB6 and RB16, and the heterocyclic group of the above-mentioned 23), RB3, RB6, RB16 and RB17 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and group C is a group consisting of 1) a halogen atom, 2) a cyano group, 3) a C1-4 alkyl group, 4) —ORC1 wherein RC1 is a hydrogen atom or a C1-4 alkyl group, 5) —NRC2RC3 wherein RC2 and RC3 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 6) —COORC4 wherein RC4 is a hydrogen atom or a C1-4 alkyl group and 7) an oxo group, whereupon p15 protein is induced. 17. A method of arresting a cell cycle in the G0/G1 phase in a mammal in need thereof comprising administering to the mammal a cell cycle arresting amount of a compound represented by the following formula [I] or a pharmaceutically acceptable salt, hydrate, or solvate thereof: wherein X1 and X2 are the same or different and each is a carbon atom or a nitrogen atom, a moiety is R1 and R2 are the same or different and each is a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, or wherein m is 0 or an integer of 1 to 4, ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R6 is wherein m is 0, and ring Cy is a C3-12 carbon ring group or a heterocyclic group, wherein the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R3, R4, and R5 are the same or different and each is a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C2-6 alkenyl group, wherein the C1-6 alkyl group and the C2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, a C3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and the C3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, or R2 and R3 are optionally linked to form a C1-4 alkylene group, or R4 and R5 are optionally linked to form a C1-4alkylene group, wherein group A is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-4 alkyl group, 5) —ORA1 wherein RA1 is a hydrogen atom or a C1-4 alkyl group, 6) —SRA2 wherein RA2 is a hydrogen atom or a C1-4 alkyl group, 7) —NRA3RA4 wherein RA3 and RA4 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 8) —COORA5 wherein RA5 is a hydrogen atom or a C1-4 alkyl group, 9) —NRA6CORA7 wherein RA6 is a hydrogen atom or a C1-4 alkyl group, RA7 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 10) —NRA8COORA9 wherein RA8 and RA9 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 11) a C3-12 carbon ring group and 12) a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, each of the C1-4 alkyl groups of the above-mentioned 4), RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8 and RA9 is optionally substituted by the same or different 1 to 3 substituents selected from the following group C, and each of the C3-12 carbon ring groups of the above-mentioned 11) and RA7, and the heterocyclic groups of 12) and RA7 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C group B is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C1-8 alkyl group, 5) a C2-4 alkenyl group, 6) a C2-4 alkynyl group, 7) —ORB1 wherein RB1 is a hydrogen atom or a C1-4 alkyl group, 8) —SRB2 wherein RB2 is a hydrogen atom or a C1-4 alkyl group, 9) —NRB3RB4 wherein RB3 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, and RB4 is a hydrogen atom or a C1-4 alkyl group, 10) —NRB5CORB6 wherein RB5 is a hydrogen atom or a C1-4 alkyl group, and RB6 is a hydrogen atom, a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 11) —NRB7COORB8 wherein RB7 and RB8 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 12) —NRB9CONRB10RB11 wherein RB9, RB10 and RB11 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 13) —NRB12CONRB13ORB14 wherein RB12, RB13 and RB14 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 14) —NRB15SO2RB16 wherein RB15 is a hydrogen atom or a C1-4 alkyl group, and RB16 is a C1-4 alkyl group, a C3-12 carbon ring group or a heterocyclic group, 15) —SO2—RB17 wherein RB17 is a C1-4 alkyl group or a heterocyclic group, 16) —SO2NRB18RB19 wherein RB18 and RB19 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 17) —P(═O)(RB20)(RB21) wherein RB20 and RB21 are the same or different and each is a C1-4 alkyl group, 18) —COORB22 wherein RB22 is a hydrogen atom or a C1-4 alkyl group, 19) —CONRB23RB24 wherein RB23 and RB24 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 20) —NRB25SO2NRB26RB27 wherein RB25, RB26 and RB27 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 21) —NRB28SO2NRB29CONRB30RB31 wherein RB28, RB29, RB30 and RB31 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 22) a C3-12 carbon ring group and 23) a heterocyclic group wherein each of the “C1-8 alkyl group” of the above-mentioned 4), and the C1-4 alkyl groups for RB1 to RB31 is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, each of the C2-4 alkenyl group of 5) and the C2-4 alkynyl group of 6) is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and each of the C3-12 carbon ring group of the above-mentioned 22), RB3, RB6 and RB16, and RB6, RB16, and the heterocyclic group of the above-mentioned 23), RB3, RB6, RB16 and RB17 optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and group C is a group consisting of 1) a halogen atom, 2) a cyano group, 3) a C1-4 alkyl group, 4) —ORC1 wherein RC1 is a hydrogen atom or a C1-4 alkyl group, 5) —NRC2RC3 wherein RC2 and RC3 are the same or different and each is a hydrogen atom or a C1-4 alkyl group, 6) —COORC4 wherein RC4 is a hydrogen atom or a C1-4 alkyl group and 7) an oxo group, whereupon the cell cycle is arrested in the G0/G1 phase. 18. The method of claim 1, wherein the undesirable cell proliferation is cancer. 19. The method of claim 18, wherein the cancer is melanoma. 20. The method of claim 18, wherein the cancer is pancreatic cancer. 21. The method of claim 18, wherein the cancer is non-small cell lung cancer. 22. The method of claim 18, wherein the cancer is acute myeloid leukemia. 23. The method of any one of claims 1, 15-17, and 18-22, further comprising administering to the mammal a therapeutic amount of at least one antitumor compound that is not a compound of the formula [I]. 24. The method of claim 23, wherein the at least one antitumor compound is an apoptosis inducer. 25. The method of claim 24, wherein the apoptosis inducer is gemcitabine. 26. The method of any one of claims 1, 15-17, and 18-22, wherein the compound of formula [I] is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof. 27. The method of claim 26, wherein the compound is the sodium salt thereof. 28. The method of claim 26, wherein the compound is the hydrate thereof. 29. The method of claim 26, wherein the compound is the acetic acid solvate thereof. 30. The method of claim 26, wherein the compound is the dimethylsulfoxide solvate thereof. 31. The method of claim 26, wherein the compound is the ethanol solvate thereof. 32. The method of claim 26, wherein the compound is the nitromethane solvate thereof. 33. The method of claim 26, wherein the compound is the chlorobenzene solvate thereof. 34. The method of claim 26, wherein the compound is the 1-pentanol solvate thereof. 35. The method of claim 26, wherein the compound is the isopropyl alcohol solvate thereof. 36. The method of claim 26, wherein the compound is the ethylene glycol solvate thereof. 37. The method of claim 26, wherein the compound is the 3-methylbutanol solvate thereof. 38. The method of claim 23, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof. 39. The method of claim 38, wherein the compound is the sodium salt thereof. 40. The method of claim 38, wherein the compound is the hydrate thereof. 41. The method of claim 38, wherein the compound is the acetic acid solvate thereof. 42. The method of claim 38, wherein the compound is the dimethylsulfoxide solvate thereof. 43. The method of claim 38, wherein the compound is the ethanol solvate thereof. 44. The method of claim 38, wherein the compound is the nitromethane solvate thereof. 45. The method of claim 38, wherein the compound is the chlorobenzene solvate thereof. 46. The method of claim 38, wherein the compound is the 1-pentanol solvate thereof. 47. The method of claim 38, wherein the compound is the isopropyl alcohol solvate thereof. 48. The method of claim 38, wherein the compound is the ethylene glycol solvate thereof. 49. The method of claim 38, wherein the compound is the 3-methylbutanol solvate thereof.