UA73522C2 - Imidazo[1,2-a]pyridine and pyrazole[2,3-a]pyridine derivatives - Google Patents

Info

Publication number

UA73522C2

UA73522C2 UA2002032241A UA2002032241A UA73522C2 UA 73522 C2 UA73522 C2 UA 73522C2 UA 2002032241 A UA2002032241 A UA 2002032241A UA 2002032241 A UA2002032241 A UA 2002032241A UA 73522 C2 UA73522 C2 UA 73522C2

Authority

UA

Ukraine

Prior art keywords

sulfamoyl

alkyl

pyrid

formula

compound

Prior art date

1999-08-21

Links

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• Global Dossier
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• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title description 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 title 1
• 150000003222 pyridines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 187
• 238000000034 method Methods 0.000 claims abstract description 122
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 107
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 99
• 150000003839 salts Chemical class 0.000 claims abstract description 45
• 150000002148 esters Chemical class 0.000 claims abstract description 42
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• -1 cyano, hydroxy Chemical group 0.000 claims description 201
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 166
• 125000000217 alkyl group Chemical group 0.000 claims description 135
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 73
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 62
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 51
• 125000000623 heterocyclic group Chemical group 0.000 claims description 46
• 229910052799 carbon Inorganic materials 0.000 claims description 43
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 41
• 230000007062 hydrolysis Effects 0.000 claims description 32
• 238000006460 hydrolysis reaction Methods 0.000 claims description 32
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 28
• 229910052736 halogen Inorganic materials 0.000 claims description 26
• 150000002367 halogens Chemical class 0.000 claims description 26
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 150000001721 carbon Chemical group 0.000 claims description 24
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
• 238000011282 treatment Methods 0.000 claims description 20
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
• 229910052794 bromium Inorganic materials 0.000 claims description 18
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 241001465754 Metazoa Species 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
• 238000006243 chemical reaction Methods 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 125000006239 protecting group Chemical group 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• 239000012634 fragment Substances 0.000 claims description 8
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 125000001589 carboacyl group Chemical group 0.000 claims description 7
• 230000003993 interaction Effects 0.000 claims description 7
• 239000003153 chemical reaction reagent Substances 0.000 claims description 6
• 208000032839 leukemia Diseases 0.000 claims description 6
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 238000009776 industrial production Methods 0.000 claims description 5
• 229910052751 metal Inorganic materials 0.000 claims description 5
• 239000002184 metal Substances 0.000 claims description 5
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
• 125000004043 oxo group Chemical group O=* 0.000 claims description 5
• 230000035755 proliferation Effects 0.000 claims description 5
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
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• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 208000038016 acute inflammation Diseases 0.000 claims description 4
• 230000006022 acute inflammation Effects 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 208000037976 chronic inflammation Diseases 0.000 claims description 4
• 230000006020 chronic inflammation Effects 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• 208000030533 eye disease Diseases 0.000 claims description 4
• 230000000893 fibroproliferative effect Effects 0.000 claims description 4
• 201000011066 hemangioma Diseases 0.000 claims description 4
• 208000017169 kidney disease Diseases 0.000 claims description 4
• 229940126601 medicinal product Drugs 0.000 claims description 4
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
• 230000000306 recurrent effect Effects 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 150000001412 amines Chemical class 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 3
• 210000001210 retinal vessel Anatomy 0.000 claims description 3
• 208000031481 Pathologic Constriction Diseases 0.000 claims description 2
• 229910052770 Uranium Inorganic materials 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
• 229910052700 potassium Inorganic materials 0.000 claims description 2
• 230000036262 stenosis Effects 0.000 claims description 2
• 208000037804 stenosis Diseases 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 125000000304 alkynyl group Chemical group 0.000 claims 1
• GRKXKNLRBZVLSN-UHFFFAOYSA-N methylamino acetate Chemical group CNOC(C)=O GRKXKNLRBZVLSN-UHFFFAOYSA-N 0.000 claims 1
• 125000002072 seryl group Chemical group 0.000 claims 1
• 238000012876 topography Methods 0.000 claims 1
• 230000022131 cell cycle Effects 0.000 abstract description 13
• 230000005764 inhibitory process Effects 0.000 abstract description 8
• 238000002360 preparation method Methods 0.000 abstract description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 1
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 abstract 1
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 abstract 1
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 abstract 1
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 abstract 1
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 abstract 1
• 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 abstract 1
• 238000001727 in vivo Methods 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
• 239000000203 mixture Substances 0.000 description 137
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 70
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
• 238000005481 NMR spectroscopy Methods 0.000 description 65
• 238000001704 evaporation Methods 0.000 description 51
• 230000008020 evaporation Effects 0.000 description 51
• 238000004587 chromatography analysis Methods 0.000 description 44
• 239000000243 solution Substances 0.000 description 42
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 34
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 230000002401 inhibitory effect Effects 0.000 description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• 101000703761 Homo sapiens Leucine-rich repeat protein SHOC-2 Proteins 0.000 description 12
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• 239000003112 inhibitor Substances 0.000 description 11
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• 230000001028 anti-proliverative effect Effects 0.000 description 9
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• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
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• 125000002252 acyl group Chemical group 0.000 description 8
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
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• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
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• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 5
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