ES2309591T3 - Pirimidinas con actividad tie2(tek). - Google Patents
Pirimidinas con actividad tie2(tek). Download PDFInfo
- Publication number
- ES2309591T3 ES2309591T3 ES04806134T ES04806134T ES2309591T3 ES 2309591 T3 ES2309591 T3 ES 2309591T3 ES 04806134 T ES04806134 T ES 04806134T ES 04806134 T ES04806134 T ES 04806134T ES 2309591 T3 ES2309591 T3 ES 2309591T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- amino
- alkoxy
- phenyl
- saturated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 230000000694 effects Effects 0.000 title description 22
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 title description 4
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 460
- -1 amino, carbamoyl Chemical group 0.000 claims abstract description 455
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 426
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 406
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 358
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 241
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 219
- 239000001257 hydrogen Substances 0.000 claims abstract description 219
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 211
- 150000001875 compounds Chemical class 0.000 claims abstract description 198
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 185
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 146
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 137
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 132
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 109
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 85
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims abstract description 79
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 78
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 71
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 69
- 239000011737 fluorine Substances 0.000 claims abstract description 69
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 68
- 125000005843 halogen group Chemical group 0.000 claims abstract description 66
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 63
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 57
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 37
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 31
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims description 110
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000004076 pyridyl group Chemical group 0.000 claims description 60
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 59
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 53
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 50
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 50
- 125000000335 thiazolyl group Chemical group 0.000 claims description 49
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 44
- 125000002883 imidazolyl group Chemical group 0.000 claims description 43
- 125000002971 oxazolyl group Chemical group 0.000 claims description 42
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 42
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 42
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 41
- 125000002541 furyl group Chemical group 0.000 claims description 41
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 41
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 41
- 125000001544 thienyl group Chemical group 0.000 claims description 41
- 125000001425 triazolyl group Chemical group 0.000 claims description 41
- 125000002619 bicyclic group Chemical group 0.000 claims description 38
- 229910052701 rubidium Inorganic materials 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 30
- 150000001412 amines Chemical class 0.000 claims description 27
- 125000000524 functional group Chemical group 0.000 claims description 27
- CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical compound FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 claims description 25
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 23
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 23
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 22
- 241001465754 Metazoa Species 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 102000012753 TIE-2 Receptor Human genes 0.000 claims description 14
- 108010090091 TIE-2 Receptor Proteins 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000012948 isocyanate Substances 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 150000001345 alkine derivatives Chemical class 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 150000002513 isocyanates Chemical class 0.000 claims description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 8
- 208000034038 Pathologic Neovascularization Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- VLJNIUYWLWKXGY-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2N)N)=N1 VLJNIUYWLWKXGY-UHFFFAOYSA-N 0.000 claims description 3
- PZZLPGXLHRRVAU-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(2-morpholin-4-ylethylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NCCN2CCOCC2)=N1 PZZLPGXLHRRVAU-UHFFFAOYSA-N 0.000 claims description 3
- FCXHLOLLFUKXQZ-UHFFFAOYSA-N 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-3-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]urea Chemical compound S1C(C(C)(C)C)=NN=C1NC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 FCXHLOLLFUKXQZ-UHFFFAOYSA-N 0.000 claims description 3
- DWDZHXCGWUTSEJ-UHFFFAOYSA-N 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-3-[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]urea Chemical compound S1C(C(C)(C)C)=NN=C1NC(=O)NC1=CC=C(C#CC=2C(=NC=NC=2N)N)C=C1 DWDZHXCGWUTSEJ-UHFFFAOYSA-N 0.000 claims description 3
- BWGJJZKSFWBNAC-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2C=C3OCCOC3=CC=2)=C1 BWGJJZKSFWBNAC-UHFFFAOYSA-N 0.000 claims description 3
- CPTWISRJCXYSKU-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(2-morpholin-4-ylphenyl)urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2C(=CC=CC=2)N2CCOCC2)=C1 CPTWISRJCXYSKU-UHFFFAOYSA-N 0.000 claims description 3
- YAQSJUMPVVARIT-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(3-methyl-1,2-oxazol-5-yl)urea Chemical compound O1N=C(C)C=C1NC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 YAQSJUMPVVARIT-UHFFFAOYSA-N 0.000 claims description 3
- KTCPCYALYMIOOL-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(3-methyl-1,2-thiazol-5-yl)urea Chemical compound S1N=C(C)C=C1NC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 KTCPCYALYMIOOL-UHFFFAOYSA-N 0.000 claims description 3
- KDZHDZUEBHEULS-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[2-(trifluoromethyl)phenyl]urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2C(=CC=CC=2)C(F)(F)F)=C1 KDZHDZUEBHEULS-UHFFFAOYSA-N 0.000 claims description 3
- HZIFWYVRZLJAMZ-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 HZIFWYVRZLJAMZ-UHFFFAOYSA-N 0.000 claims description 3
- OFDYOMFJLKLQII-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1 OFDYOMFJLKLQII-UHFFFAOYSA-N 0.000 claims description 3
- UUACONKSMKMZJG-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)NC=2N=CC=C(C=2)C(F)(F)F)=C1 UUACONKSMKMZJG-UHFFFAOYSA-N 0.000 claims description 3
- MUZKROVMLJMCDW-UHFFFAOYSA-N 1-[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(3-methyl-1,2-oxazol-5-yl)urea Chemical compound O1N=C(C)C=C1NC(=O)NC1=CC=C(C#CC=2C(=NC=NC=2N)N)C=C1 MUZKROVMLJMCDW-UHFFFAOYSA-N 0.000 claims description 3
- ACOXCIWILXLVGZ-UHFFFAOYSA-N 1-[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(3-methyl-1,2-thiazol-5-yl)urea Chemical compound S1N=C(C)C=C1NC(=O)NC1=CC=C(C#CC=2C(=NC=NC=2N)N)C=C1 ACOXCIWILXLVGZ-UHFFFAOYSA-N 0.000 claims description 3
- HHYNEZCJBZEGJN-UHFFFAOYSA-N 1-[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound NC1=NC=NC(N)=C1C#CC(C=C1)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1F HHYNEZCJBZEGJN-UHFFFAOYSA-N 0.000 claims description 3
- ZWSLELFBRLVYTM-UHFFFAOYSA-N 1-[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea Chemical compound NC1=NC=NC(N)=C1C#CC(C=C1)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC=N1 ZWSLELFBRLVYTM-UHFFFAOYSA-N 0.000 claims description 3
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- XXYSCRDEVSWVBF-UHFFFAOYSA-N n-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-2-[4-(trifluoromethyl)phenyl]acetamide Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)CC=2C=CC(=CC=2)C(F)(F)F)=C1 XXYSCRDEVSWVBF-UHFFFAOYSA-N 0.000 claims description 3
- YPFSKXWYQIKSJC-UHFFFAOYSA-N n-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-2-phenylacetamide Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)CC=2C=CC=CC=2)=C1 YPFSKXWYQIKSJC-UHFFFAOYSA-N 0.000 claims description 3
- VSSDDLKIHUMWEF-UHFFFAOYSA-N n-[3-[[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]carbamoylamino]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2N)N)=C1 VSSDDLKIHUMWEF-UHFFFAOYSA-N 0.000 claims description 3
- LULWEIAEPUVWBM-UHFFFAOYSA-N n-[3-[[4-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]carbamoylamino]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C#CC=2C(=NC=NC=2N)N)=C1 LULWEIAEPUVWBM-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- YMDNBJLXYNUJRO-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(2-hydroxyethylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NCCO)=N1 YMDNBJLXYNUJRO-UHFFFAOYSA-N 0.000 claims description 2
- YRIBYGOJNRCLFY-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(2-pyrrolidin-1-ylethylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NCCN2CCCC2)=N1 YRIBYGOJNRCLFY-UHFFFAOYSA-N 0.000 claims description 2
- UZWKGOYJOBEWIT-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(methylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound CNC1=NC=NC=C1C#CC1=CC=CC(NC(=O)NC2=NOC(=C2)C(C)(C)C)=C1 UZWKGOYJOBEWIT-UHFFFAOYSA-N 0.000 claims description 2
- JVUZXRDTWTVVDM-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-[(2,4-dimethoxyphenyl)methylamino]pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound COC1=CC(OC)=CC=C1CNC1=NC=NC=C1C#CC1=CC=CC(NC(=O)NC2=NOC(=C2)C(C)(C)C)=C1 JVUZXRDTWTVVDM-UHFFFAOYSA-N 0.000 claims description 2
- DWGGMXXNOWNENR-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-[(5-tert-butyl-1,2-oxazol-3-yl)amino]pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NC2=NOC(=C2)C(C)(C)C)=N1 DWGGMXXNOWNENR-UHFFFAOYSA-N 0.000 claims description 2
- CKBLLSJJAWXCCF-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-[3-(propan-2-ylamino)propylamino]pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound CC(C)NCCCNC1=NC=NC=C1C#CC1=CC=CC(NC(=O)NC2=NOC(=C2)C(C)(C)C)=C1 CKBLLSJJAWXCCF-UHFFFAOYSA-N 0.000 claims description 2
- ZZKARPKXOYEXRT-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(1-methylpiperidin-4-yl)urea Chemical compound C1CN(C)CCC1NC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 ZZKARPKXOYEXRT-UHFFFAOYSA-N 0.000 claims description 2
- FJIMSKSYCYHGCJ-UHFFFAOYSA-N 1-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-3-(1-propylpiperidin-4-yl)urea Chemical compound C1CN(CCC)CCC1NC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 FJIMSKSYCYHGCJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- KJJHHJAPCQBAMQ-UHFFFAOYSA-N n-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-2-(2-methoxyphenyl)acetamide Chemical compound COC1=CC=CC=C1CC(=O)NC1=CC=CC(C#CC=2C(=NC=NC=2N)N)=C1 KJJHHJAPCQBAMQ-UHFFFAOYSA-N 0.000 claims description 2
- JSHVGFGVFXHTJB-UHFFFAOYSA-N n-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-2-(3-methoxyphenyl)acetamide Chemical compound COC1=CC=CC(CC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2N)N)=C1 JSHVGFGVFXHTJB-UHFFFAOYSA-N 0.000 claims description 2
- VCRPQCYQIQQFMT-UHFFFAOYSA-N n-[3-[2-(4,6-diaminopyrimidin-5-yl)ethynyl]phenyl]-2-[3-(trifluoromethyl)phenyl]acetamide Chemical compound NC1=NC=NC(N)=C1C#CC1=CC=CC(NC(=O)CC=2C=C(C=CC=2)C(F)(F)F)=C1 VCRPQCYQIQQFMT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 claims description 2
- KYJHTGLFBHFWGM-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(2-piperidin-1-ylethylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NCCN2CCCCC2)=N1 KYJHTGLFBHFWGM-UHFFFAOYSA-N 0.000 claims 1
- WSDJQQDDLYWCQC-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-[2-[4-(3-morpholin-4-ylpropylamino)pyrimidin-5-yl]ethynyl]phenyl]urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=C(C=CC=2)C#CC=2C(=NC=NC=2)NCCCN2CCOCC2)=N1 WSDJQQDDLYWCQC-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0330001A GB0330001D0 (en) | 2003-12-24 | 2003-12-24 | Compounds |
| GB0330001 | 2003-12-24 | ||
| GB0416850 | 2004-07-29 | ||
| GB0416850A GB0416850D0 (en) | 2004-07-29 | 2004-07-29 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2309591T3 true ES2309591T3 (es) | 2008-12-16 |
Family
ID=34712716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04806134T Expired - Lifetime ES2309591T3 (es) | 2003-12-24 | 2004-12-20 | Pirimidinas con actividad tie2(tek). |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20080027076A1 (https=) |
| EP (1) | EP1737462B1 (https=) |
| JP (1) | JP2007517006A (https=) |
| AR (1) | AR046996A1 (https=) |
| AT (1) | ATE402705T1 (https=) |
| DE (1) | DE602004015509D1 (https=) |
| ES (1) | ES2309591T3 (https=) |
| TW (1) | TW200524607A (https=) |
| UY (1) | UY28700A1 (https=) |
| WO (1) | WO2005060969A1 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT410913B (de) * | 2001-08-14 | 2003-08-25 | Schelling Anlagenbau Gmbh | Auflagetisch für eine trennsäge mit einem maschinentisch |
| EP1737463B1 (en) * | 2003-12-24 | 2008-12-03 | AstraZeneca AB | Pyrimidines with tie2 (tek) activity |
| US7776869B2 (en) * | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| US20100048543A1 (en) * | 2005-02-01 | 2010-02-25 | Astrazeneca Ab | Pyrimidine compounds having ties (tek) inhibitory activity |
| WO2006082371A1 (en) * | 2005-02-01 | 2006-08-10 | Astrazeneca Ab | Pyrimidine compounds having tie2 (tek) inhibitory activity |
| GB0502418D0 (en) * | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| EP1893605A2 (en) * | 2005-03-31 | 2008-03-05 | AstraZeneca AB | Saminopyrimidine derivates with tie2 inhibiting activity |
| SI2495016T1 (sl) * | 2005-12-23 | 2020-04-30 | Ariad Pharmaceuticals, Inc. | Biciklične heteroarilne spojine |
| AU2015210454B2 (en) * | 2005-12-23 | 2016-10-27 | Takeda Pharmaceuticals U.S.A., Inc. | Bicyclic heteroaryl compounds |
| AU2013201243A1 (en) * | 2005-12-23 | 2013-03-28 | Ariad Pharmaceuticals, Inc. | Bicyclic heteroaryl compounds |
| CN101389338B (zh) * | 2005-12-23 | 2013-06-26 | 阿里亚德医药股份有限公司 | 双环杂芳基化合物 |
| AU2007249924B2 (en) | 2006-05-08 | 2013-07-04 | Ariad Pharmaceuticals, Inc. | Acetylenic heteroaryl compounds |
| BRPI0710331A2 (pt) | 2006-05-08 | 2012-03-20 | Ariad Pharmaceuticals, Inc | Compostos heteroarila monocíclicos para tratamento de câncer e composição |
| EP2022785A1 (en) | 2007-06-20 | 2009-02-11 | Bayer Schering Pharma Aktiengesellschaft | Alkynylpyrimidines as Tie2 kinase inhibitors |
| EP2070929A1 (en) * | 2007-12-11 | 2009-06-17 | Bayer Schering Pharma Aktiengesellschaft | Alkynylaryl compounds and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| PE20110196A1 (es) | 2008-07-29 | 2011-04-03 | Boehringer Ingelheim Int | 5-alquinil-pirimidinas |
| EP2365809B8 (en) | 2008-11-12 | 2018-10-10 | Ariad Pharmaceuticals, Inc. | Pyrazinopyrazines and derivatives as kinase inhibitors |
| US8633183B2 (en) | 2010-01-26 | 2014-01-21 | Boehringer Ingelheim International Gmbh | 5-alkynyl-pyrimidines |
| US8618111B2 (en) * | 2010-01-26 | 2013-12-31 | Boehringer Ingelheim International Gmbh | 5-alkynyl-pyrimidines |
| CA3022250A1 (en) | 2012-12-12 | 2014-06-12 | Ariad Pharmaceuticals, Inc. | Crystalline forms of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride |
| JP6665154B2 (ja) * | 2014-07-17 | 2020-03-13 | ノース・アンド・サウス・ブラザー・ファーマシー・インベストメント・カンパニー・リミテッド | 置換尿素誘導体及びその薬学的使用 |
| ES2921257T3 (es) * | 2016-06-20 | 2022-08-22 | Daegu Gyeongbuk Medical Innovation Found | Nuevo derivado de imidazopiridina, procedimiento para prepararlo y composición farmacéutica que contiene el mismo como ingrediente activo para prevenir o tratar el cáncer |
| ES2889749T3 (es) * | 2017-07-13 | 2022-01-13 | Sunshine Lake Pharma Co Ltd | Sal de derivado de urea sustituido y uso de la misma en medicina |
| US20210284647A1 (en) * | 2018-07-10 | 2021-09-16 | Voronoibio Inc. | N-(3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylphenyl)-5-phenyl-4,5-dihydro-1h-pyrazole-1-carboxamide derivative, and pharmaceutical composition containing same as active ingredient for treating kinase-related diseases |
| US11746110B2 (en) | 2018-07-17 | 2023-09-05 | Shenzhen Targetrx, Inc. | Alkynyl (hetero) aromatic ring compounds used for inhibiting protein kinase activity |
| JP7505719B2 (ja) * | 2020-02-28 | 2024-06-25 | テグ－キョンプク メディカル イノベーション ファウンデーション | ３－（（８－（（１Ｈ－ピラゾール－４－イル）アミノ）イミダゾ［１，２－ａ］ピリジン－３－イル）エチニル）－Ｎ－フェニルベンズアミド誘導体、その調製法、それを活性成分として含有する癌の予防用又は治療用医薬組成物 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4064671B2 (ja) * | 2000-02-25 | 2008-03-19 | エフ．ホフマン−ラ ロシュ アーゲー | アデノシン受容体モジュレーター |
| DK1303495T3 (da) * | 2000-07-24 | 2010-09-20 | Krenitsky Pharmaceuticals Inc | Substituerede 5-alkylnylpyrimidiner med neurotrofisk aktivitet |
| US20030225273A1 (en) * | 2002-03-21 | 2003-12-04 | Michaelides Michael R. | Thiopyrimidine and isothiazolopyrimidine kinase inhibitors |
| US20030199525A1 (en) * | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
-
2004
- 2004-12-20 EP EP04806134A patent/EP1737462B1/en not_active Expired - Lifetime
- 2004-12-20 ES ES04806134T patent/ES2309591T3/es not_active Expired - Lifetime
- 2004-12-20 DE DE602004015509T patent/DE602004015509D1/de not_active Expired - Fee Related
- 2004-12-20 JP JP2006546305A patent/JP2007517006A/ja active Pending
- 2004-12-20 US US10/596,740 patent/US20080027076A1/en not_active Abandoned
- 2004-12-20 AT AT04806134T patent/ATE402705T1/de not_active IP Right Cessation
- 2004-12-20 WO PCT/GB2004/005332 patent/WO2005060969A1/en not_active Ceased
- 2004-12-23 UY UY28700A patent/UY28700A1/es not_active Application Discontinuation
- 2004-12-24 TW TW093140595A patent/TW200524607A/zh unknown
- 2004-12-27 AR ARP040104907A patent/AR046996A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007517006A (ja) | 2007-06-28 |
| US20080027076A1 (en) | 2008-01-31 |
| UY28700A1 (es) | 2005-07-29 |
| WO2005060969A1 (en) | 2005-07-07 |
| ATE402705T1 (de) | 2008-08-15 |
| HK1102045A1 (en) | 2007-11-02 |
| EP1737462A1 (en) | 2007-01-03 |
| TW200524607A (en) | 2005-08-01 |
| DE602004015509D1 (de) | 2008-09-11 |
| AR046996A1 (es) | 2006-01-04 |
| EP1737462B1 (en) | 2008-07-30 |
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