PT1187592E - Antagonistas dos receptores de integrina alfa v - Google Patents

Info

Publication number

PT1187592E

PT1187592E PT00942652T PT00942652T PT1187592E PT 1187592 E PT1187592 E PT 1187592E PT 00942652 T PT00942652 T PT 00942652T PT 00942652 T PT00942652 T PT 00942652T PT 1187592 E PT1187592 E PT 1187592E

Authority

PT

Portugal

Prior art keywords

alkyl

alkylamino

oxo

aryl

tetrahydro

Prior art date

1999-06-02

Links

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• 229940127449 Integrin Receptor Antagonists Drugs 0.000 title abstract description 14
• 150000001875 compounds Chemical class 0.000 claims abstract description 113
• 108010044426 integrins Proteins 0.000 claims abstract description 37
• 102000006495 integrins Human genes 0.000 claims abstract description 37
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
• 239000005557 antagonist Substances 0.000 claims abstract description 27
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
• 230000033115 angiogenesis Effects 0.000 claims abstract description 22
• 201000010099 disease Diseases 0.000 claims abstract description 22
• 206010061218 Inflammation Diseases 0.000 claims abstract description 17
• 201000011510 cancer Diseases 0.000 claims abstract description 17
• 230000004054 inflammatory process Effects 0.000 claims abstract description 17
• 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 15
• 208000002780 macular degeneration Diseases 0.000 claims abstract description 15
• 208000037803 restenosis Diseases 0.000 claims abstract description 15
• 230000004614 tumor growth Effects 0.000 claims abstract description 14
• 230000003612 virological effect Effects 0.000 claims abstract description 13
• 206010003246 arthritis Diseases 0.000 claims abstract description 11
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 9
• -1 aryl- C1-6 alkyl Chemical group 0.000 claims description 78
• 239000000203 mixture Substances 0.000 claims description 44
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
• 125000003118 aryl group Chemical group 0.000 claims description 32
• 210000002997 osteoclast Anatomy 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 claims description 23
• FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 22
• 125000000217 alkyl group Chemical group 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 230000000694 effects Effects 0.000 claims description 18
• 239000003112 inhibitor Substances 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 14
• 230000003042 antagnostic effect Effects 0.000 claims description 13
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 150000002148 esters Chemical class 0.000 claims description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical group 0.000 claims description 12
• 229940122361 Bisphosphonate Drugs 0.000 claims description 11
• 150000004663 bisphosphonates Chemical class 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 9
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 8
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 230000002265 prevention Effects 0.000 claims description 8
• 125000005493 quinolyl group Chemical group 0.000 claims description 8
• 229940044551 receptor antagonist Drugs 0.000 claims description 8
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• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
• 108091006112 ATPases Proteins 0.000 claims description 7
• 102000057290 Adenosine Triphosphatases Human genes 0.000 claims description 7
• 206010027476 Metastases Diseases 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 229920006395 saturated elastomer Polymers 0.000 claims description 7
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 6
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 6
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 6
• 239000013543 active substance Substances 0.000 claims description 6
• 125000004442 acylamino group Chemical group 0.000 claims description 6
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 230000009401 metastasis Effects 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• 102100033367 Appetite-regulating hormone Human genes 0.000 claims description 5
• 101710111255 Appetite-regulating hormone Proteins 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
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• 125000005842 heteroatom Chemical group 0.000 claims description 5
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• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
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• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 5
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
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• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 4
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 4
• 230000001028 anti-proliverative effect Effects 0.000 claims description 4
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
• 231100000433 cytotoxic Toxicity 0.000 claims description 4
• 230000001472 cytotoxic effect Effects 0.000 claims description 4
• 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 4
• 102000004171 Cathepsin K Human genes 0.000 claims description 3
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• 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 3
• 229940122091 Geranylgeranyltransferase inhibitor Drugs 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
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• 102000037865 fusion proteins Human genes 0.000 claims description 3
• 239000003102 growth factor Substances 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 229910052757 nitrogen Inorganic materials 0.000 claims description 3
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
• CAKRAHQRJGUPIG-UHFFFAOYSA-M sodium;[4-azaniumyl-1-hydroxy-1-[hydroxy(oxido)phosphoryl]butyl]-hydroxyphosphinate Chemical group [Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O CAKRAHQRJGUPIG-UHFFFAOYSA-M 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims description 2
• NMOYMTRZYRAJPD-UHFFFAOYSA-N 3-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(6,7,8,9-tetrahydro-5h-pyrido[2,3-b]azepin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCCN2)C2=N1 NMOYMTRZYRAJPD-UHFFFAOYSA-N 0.000 claims description 2
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 2
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• 101100481406 Mus musculus Tie1 gene Proteins 0.000 claims description 2
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• 101100445392 Xenopus laevis ephb3 gene Proteins 0.000 claims description 2
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• 210000001339 epidermal cell Anatomy 0.000 claims description 2
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims description 2
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
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• MQEYZBZPDZEAEE-NRFANRHFSA-N (2s)-2-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(6,7,8,9-tetrahydro-5h-pyrido[2,3-b]azepin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCCN2)C2=N1 MQEYZBZPDZEAEE-NRFANRHFSA-N 0.000 claims 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims 1
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