AU2012351712B2 - Pyrazolopyridine derivatives, preparation process therefor and therapeutic use thereof - Google Patents

Info

Publication number

AU2012351712B2

AU2012351712B2 AU2012351712A AU2012351712A AU2012351712B2 AU 2012351712 B2 AU2012351712 B2 AU 2012351712B2 AU 2012351712 A AU2012351712 A AU 2012351712A AU 2012351712 A AU2012351712 A AU 2012351712A AU 2012351712 B2 AU2012351712 B2 AU 2012351712B2

Authority

AU

Australia

Prior art keywords

group

pyrazolo

phenyl

pyridin

trifluoromethyl

Prior art date

2011-12-14

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.)

Ceased

Links

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• 238000002360 preparation method Methods 0.000 title claims description 5
• 230000001225 therapeutic effect Effects 0.000 title abstract description 4
• 150000005229 pyrazolopyridines Chemical class 0.000 title description 2
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 150000001875 compounds Chemical class 0.000 claims description 177
• 229910052757 nitrogen Inorganic materials 0.000 claims description 120
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 81
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 78
• 125000000217 alkyl group Chemical group 0.000 claims description 72
• 238000011282 treatment Methods 0.000 claims description 50
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 49
• 125000005842 heteroatom Chemical group 0.000 claims description 48
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 46
• 125000003118 aryl group Chemical group 0.000 claims description 44
• 125000004076 pyridyl group Chemical group 0.000 claims description 43
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
• 125000001424 substituent group Chemical group 0.000 claims description 38
• 206010028980 Neoplasm Diseases 0.000 claims description 37
• 229920006395 saturated elastomer Polymers 0.000 claims description 35
• 238000000034 method Methods 0.000 claims description 31
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 22
• 238000002560 therapeutic procedure Methods 0.000 claims description 22
• 230000002265 prevention Effects 0.000 claims description 21
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 21
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
• 238000006243 chemical reaction Methods 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 15
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 15
• 239000003446 ligand Substances 0.000 claims description 14
• 238000006069 Suzuki reaction reaction Methods 0.000 claims description 13
• 150000002148 esters Chemical class 0.000 claims description 13
• 125000004432 carbon atom Chemical group C* 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
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• 208000008919 achondroplasia Diseases 0.000 claims description 11
• 239000003054 catalyst Substances 0.000 claims description 11
• 229910052763 palladium Inorganic materials 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
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• 125000001544 thienyl group Chemical group 0.000 claims description 10
• 230000002792 vascular Effects 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000004434 sulfur atom Chemical group 0.000 claims description 9
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 8
• 238000005804 alkylation reaction Methods 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
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• YUVBHWNSSUFVNU-UHFFFAOYSA-N 2-amino-5-[4-(difluoromethyl)-1-methylpyrazolo[3,4-b]pyridin-6-yl]benzonitrile Chemical compound N1=C2N(C)N=CC2=C(C(F)F)C=C1C1=CC=C(N)C(C#N)=C1 YUVBHWNSSUFVNU-UHFFFAOYSA-N 0.000 claims description 4
• AMDQRIBWSYJGCS-UHFFFAOYSA-N 2-fluoro-5-[3-phenyl-4-(trifluoromethyl)-2h-pyrazolo[3,4-b]pyridin-6-yl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(C2=NC3=NNC(=C3C(=C2)C(F)(F)F)C=2C=CC=CC=2)=C1 AMDQRIBWSYJGCS-UHFFFAOYSA-N 0.000 claims description 4
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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• FNPZYDSGVUZXLM-UHFFFAOYSA-N 2-amino-5-[4-(difluoromethyl)-1h-pyrazolo[3,4-b]pyridin-6-yl]benzonitrile Chemical compound C1=C(C#N)C(N)=CC=C1C1=CC(C(F)F)=C(C=NN2)C2=N1 FNPZYDSGVUZXLM-UHFFFAOYSA-N 0.000 claims description 3
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• JFBYMYUTFVTRGH-UHFFFAOYSA-N 4-[5-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]pyridin-2-yl]morpholine Chemical compound C12=C(C(F)(F)F)C=C(C=3C=NC(=CC=3)N3CCOCC3)N=C2N(C)N=C1C1=CC=CC=C1 JFBYMYUTFVTRGH-UHFFFAOYSA-N 0.000 claims description 3
• FTZOTEZEJXGMME-UHFFFAOYSA-N 4-[[3-[1-methyl-3-pyridin-3-yl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]phenyl]methyl]morpholine Chemical compound C12=C(C(F)(F)F)C=C(C=3C=C(CN4CCOCC4)C=CC=3)N=C2N(C)N=C1C1=CC=CN=C1 FTZOTEZEJXGMME-UHFFFAOYSA-N 0.000 claims description 3
• AUBQNGHWNDGCEQ-UHFFFAOYSA-N 5-(4-carbamoyl-3-phenyl-2h-pyrazolo[3,4-b]pyridin-6-yl)-2-fluorobenzoic acid Chemical compound C=12C(C(=O)N)=CC(C=3C=C(C(F)=CC=3)C(O)=O)=NC2=NNC=1C1=CC=CC=C1 AUBQNGHWNDGCEQ-UHFFFAOYSA-N 0.000 claims description 3
• XDMHMPLVHGTYKS-UHFFFAOYSA-N 5-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]-1,3-benzothiazole Chemical compound C12=C(C(F)(F)F)C=C(C=3C=C4N=CSC4=CC=3)N=C2N(C)N=C1C1=CC=CC=C1 XDMHMPLVHGTYKS-UHFFFAOYSA-N 0.000 claims description 3
• QPWPGHMKKMZBOQ-UHFFFAOYSA-N 5-[4-(difluoromethyl)-3-phenyl-2h-pyrazolo[3,4-b]pyridin-6-yl]-2-fluorobenzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(C2=NC3=NNC(=C3C(C(F)F)=C2)C=2C=CC=CC=2)=C1 QPWPGHMKKMZBOQ-UHFFFAOYSA-N 0.000 claims description 3
• AJEVIKZWKGEOMV-UHFFFAOYSA-N 6-(4-amino-3-cyanophenyl)-3-phenyl-2h-pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C(=O)N)=CC(C=3C=C(C(N)=CC=3)C#N)=NC2=NNC=1C1=CC=CC=C1 AJEVIKZWKGEOMV-UHFFFAOYSA-N 0.000 claims description 3
• IZNNHNMWHCIARM-UHFFFAOYSA-N 6-(4-methoxyphenyl)-1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC(C(F)(F)F)=C(C(=NN2C)C=3C=CC=CC=3)C2=N1 IZNNHNMWHCIARM-UHFFFAOYSA-N 0.000 claims description 3
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• 206010059394 acanthoma Diseases 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 201000011539 clear cell acanthoma Diseases 0.000 claims description 3
• 125000005434 dihydrobenzoxazinyl group Chemical group O1N(CCC2=C1C=CC=C2)* 0.000 claims description 3
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• 125000001041 indolyl group Chemical group 0.000 claims description 3
• ZRLVMLPJLRFIPC-UHFFFAOYSA-N n,n-dimethyl-3-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]aniline Chemical compound CN(C)C1=CC=CC(C=2N=C3N(C)N=C(C3=C(C=2)C(F)(F)F)C=2C=CC=CC=2)=C1 ZRLVMLPJLRFIPC-UHFFFAOYSA-N 0.000 claims description 3
• IMVTZQZAEMKICY-UHFFFAOYSA-N n,n-dimethyl-3-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]benzamide Chemical compound CN(C)C(=O)C1=CC=CC(C=2N=C3N(C)N=C(C3=C(C=2)C(F)(F)F)C=2C=CC=CC=2)=C1 IMVTZQZAEMKICY-UHFFFAOYSA-N 0.000 claims description 3
• XVGZTBUPQTVEMF-UHFFFAOYSA-N n,n-dimethyl-4-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1=CC(C(F)(F)F)=C(C(=NN2C)C=3C=CC=CC=3)C2=N1 XVGZTBUPQTVEMF-UHFFFAOYSA-N 0.000 claims description 3
• XEQVQPJLLLSEFU-UHFFFAOYSA-N n-methyl-3-[3-phenyl-4-(trifluoromethyl)-2h-pyrazolo[3,4-b]pyridin-6-yl]benzamide Chemical compound CNC(=O)C1=CC=CC(C2=NC3=NNC(=C3C(=C2)C(F)(F)F)C=2C=CC=CC=2)=C1 XEQVQPJLLLSEFU-UHFFFAOYSA-N 0.000 claims description 3
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