SK13082003A3 - Pyrazolopyrimidíny ako terapeutické prostriedky - Google Patents

Info

Publication number

SK13082003A3

SK13082003A3 SK1308-2003A SK13082003A SK13082003A3 SK 13082003 A3 SK13082003 A3 SK 13082003A3 SK 13082003 A SK13082003 A SK 13082003A SK 13082003 A3 SK13082003 A3 SK 13082003A3

Authority

SK

Slovakia

Prior art keywords

substituted

unsubstituted

alkyl

group

independently

Prior art date

2001-03-22

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• 239000003814 drug Substances 0.000 title description 15
• 229940124597 therapeutic agent Drugs 0.000 title description 3
• APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 399
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• 239000000651 prodrug Substances 0.000 claims abstract description 35
• 229940002612 prodrug Drugs 0.000 claims abstract description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 316
• -1 imidazo [2,1-b] [1,3] thiazolyl Chemical group 0.000 claims description 301
• 125000003118 aryl group Chemical group 0.000 claims description 189
• 229910052739 hydrogen Inorganic materials 0.000 claims description 174
• 239000001257 hydrogen Substances 0.000 claims description 164
• 125000001424 substituent group Chemical group 0.000 claims description 118
• 238000000034 method Methods 0.000 claims description 108
• 125000000623 heterocyclic group Chemical group 0.000 claims description 104
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 99
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 98
• 229910052757 nitrogen Inorganic materials 0.000 claims description 94
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 92
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
• 125000001072 heteroaryl group Chemical group 0.000 claims description 81
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 80
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 77
• 201000010099 disease Diseases 0.000 claims description 64
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 57
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
• 230000000694 effects Effects 0.000 claims description 57
• 125000003545 alkoxy group Chemical group 0.000 claims description 54
• 239000000203 mixture Substances 0.000 claims description 53
• 229910052736 halogen Inorganic materials 0.000 claims description 49
• 150000002367 halogens Chemical class 0.000 claims description 49
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
• 229910052717 sulfur Inorganic materials 0.000 claims description 48
• 102000001253 Protein Kinase Human genes 0.000 claims description 47
• 108060006633 protein kinase Proteins 0.000 claims description 47
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 42
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
• 229910004013 NO 2 Inorganic materials 0.000 claims description 41
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• 229910052760 oxygen Inorganic materials 0.000 claims description 40
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 38
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• 239000002207 metabolite Substances 0.000 claims description 35
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• 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 31
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 29
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 29
• 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 29
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 29
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000002541 furyl group Chemical group 0.000 claims description 28
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• 208000035475 disorder Diseases 0.000 claims description 26
• 229910052731 fluorine Inorganic materials 0.000 claims description 26
• 125000004076 pyridyl group Chemical group 0.000 claims description 26
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• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 22
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 125000001544 thienyl group Chemical group 0.000 claims description 22
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 21
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• 125000002883 imidazolyl group Chemical group 0.000 claims description 21
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• 125000005518 carboxamido group Chemical group 0.000 claims description 20
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
• 125000001041 indolyl group Chemical group 0.000 claims description 20
• 125000002971 oxazolyl group Chemical group 0.000 claims description 20
• 231100000397 ulcer Toxicity 0.000 claims description 20
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• 125000000168 pyrrolyl group Chemical group 0.000 claims description 19
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 18
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
• 230000008569 process Effects 0.000 claims description 17
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 17
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 16
• 229910052698 phosphorus Inorganic materials 0.000 claims description 16
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 15
• 229910052801 chlorine Inorganic materials 0.000 claims description 15
• 239000003102 growth factor Substances 0.000 claims description 15
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 15
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
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• 125000001624 naphthyl group Chemical group 0.000 claims description 13
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• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 12
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 12
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 11
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• 125000003368 amide group Chemical group 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 11
• 125000002837 carbocyclic group Chemical group 0.000 claims description 11
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 11
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 11
• 208000011580 syndromic disease Diseases 0.000 claims description 11
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
• 125000005110 aryl thio group Chemical group 0.000 claims description 10
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 10
• 229910052740 iodine Inorganic materials 0.000 claims description 10
• 230000003287 optical effect Effects 0.000 claims description 10
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 10
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 10
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
• 102100040681 Platelet-derived growth factor C Human genes 0.000 claims description 9
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• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 9
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• 125000001786 isothiazolyl group Chemical group 0.000 claims description 9
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• DLAJQEFZFUKNBV-UHFFFAOYSA-N 4,4,5,5-tetramethyl-n-phenyl-1,3,2-dioxaborolan-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1NC1=CC=CC=C1 DLAJQEFZFUKNBV-UHFFFAOYSA-N 0.000 claims description 8
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