SK287311B6 - Substituované xantíny, lieková kompozícia s ich obsahom, ich použitie a spôsob ich prípravy - Google Patents

Info

Publication number

SK287311B6

SK287311B6 SK663-2002A SK6632002A SK287311B6 SK 287311 B6 SK287311 B6 SK 287311B6 SK 6632002 A SK6632002 A SK 6632002A SK 287311 B6 SK287311 B6 SK 287311B6

Authority

SK

Slovakia

Prior art keywords

compound

dipropyl

bicyclo

dioxo

tetrahydro

Prior art date

1999-11-12

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 264
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims description 23
• 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 title claims description 3
• 239000003814 drug Chemical class 0.000 title description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
• 238000002360 preparation method Methods 0.000 claims abstract description 14
• 201000010099 disease Diseases 0.000 claims abstract description 11
• 210000003169 central nervous system Anatomy 0.000 claims abstract description 6
• 230000000747 cardiac effect Effects 0.000 claims abstract description 5
• 230000003412 degenerative effect Effects 0.000 claims abstract description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 208000023504 respiratory system disease Diseases 0.000 claims abstract description 5
• 239000000203 mixture Substances 0.000 claims description 175
• -1 aldehydo Chemical group 0.000 claims description 162
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 46
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 46
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 29
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 239000002253 acid Substances 0.000 claims description 25
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 23
• 229960005305 adenosine Drugs 0.000 claims description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
• 150000001299 aldehydes Chemical class 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 17
• ULGKOBWVPCWKOE-UHFFFAOYSA-N 1-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)bicyclo[2.2.2]octane-4-carboxylic acid Chemical compound C1CC(C(O)=O)(CC2)CCC12C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 ULGKOBWVPCWKOE-UHFFFAOYSA-N 0.000 claims description 15
• 150000002148 esters Chemical class 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• JMEHHVKPUQMNOZ-UHFFFAOYSA-N 8-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound C1CC(O)(CC2)CCC12C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 JMEHHVKPUQMNOZ-UHFFFAOYSA-N 0.000 claims description 11
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 150000004702 methyl esters Chemical class 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000005080 alkoxycarbonylalkenyl group Chemical group 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 229940075420 xanthine Drugs 0.000 claims description 9
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
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• 150000002367 halogens Chemical group 0.000 claims description 8
• FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 8
• 125000002252 acyl group Chemical group 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000000304 alkynyl group Chemical group 0.000 claims description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 206010019280 Heart failures Diseases 0.000 claims description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
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• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 150000001450 anions Chemical class 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 208000013403 hyperactivity Diseases 0.000 claims description 4
• 201000006370 kidney failure Diseases 0.000 claims description 4
• YSEQNZOXHCKLOG-UHFFFAOYSA-N 2-methyl-octanoic acid Chemical compound CCCCCCC(C)C(O)=O YSEQNZOXHCKLOG-UHFFFAOYSA-N 0.000 claims description 3
• VPQZQQILWCCMPS-UHFFFAOYSA-N 3-[4-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)-1-bicyclo[2.2.2]octanyl]prop-2-enoic acid Chemical compound C1CC(C=CC(O)=O)(CC2)CCC12C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 VPQZQQILWCCMPS-UHFFFAOYSA-N 0.000 claims description 3
• QRNZEQUDMOASPY-UHFFFAOYSA-N 8-[4-(hydroxymethyl)cuban-1-yl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C(=O)N(CCC)C2=C1NC(C13C4C5C1C1C3C4C51CO)=N2 QRNZEQUDMOASPY-UHFFFAOYSA-N 0.000 claims description 3
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
• 206010061216 Infarction Diseases 0.000 claims description 3
• 229910019142 PO4 Inorganic materials 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
• 208000008784 apnea Diseases 0.000 claims description 3
• MPLAMJZRRHSDCU-UHFFFAOYSA-N bicyclo[2.2.2]octane-4-carbaldehyde Chemical compound C1CC2CCC1(C=O)CC2 MPLAMJZRRHSDCU-UHFFFAOYSA-N 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 206010013932 dyslexia Diseases 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 230000007971 neurological deficit Effects 0.000 claims description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
• 239000010452 phosphate Substances 0.000 claims description 3
• 150000003014 phosphoric acid esters Chemical class 0.000 claims description 3
• 150000003839 salts Chemical class 0.000 claims description 3
• 125000003107 substituted aryl group Chemical group 0.000 claims description 3
• 230000009529 traumatic brain injury Effects 0.000 claims description 3
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 2
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
• FDIIYUJHLVKFBF-UHFFFAOYSA-N 8-(2-hydroxy-5-bicyclo[3.2.1]octanyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound C1C(C(O)CC2)CCC12C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 FDIIYUJHLVKFBF-UHFFFAOYSA-N 0.000 claims description 2
• VMAQWUKPAQYHQU-UHFFFAOYSA-N 8-(5-hydroxy-1-bicyclo[3.2.2]nonanyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound C1CC(O)(CCC2)CCC12C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 VMAQWUKPAQYHQU-UHFFFAOYSA-N 0.000 claims description 2
• 101150065749 Churc1 gene Proteins 0.000 claims description 2
• 229910004727 OSO3H Inorganic materials 0.000 claims description 2
• 206010030113 Oedema Diseases 0.000 claims description 2
• 229910018830 PO3H Inorganic materials 0.000 claims description 2
• 102100038239 Protein Churchill Human genes 0.000 claims description 2
• 125000004442 acylamino group Chemical group 0.000 claims description 2
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 2
• 230000003042 antagnostic effect Effects 0.000 claims description 2
• 230000002490 cerebral effect Effects 0.000 claims description 2
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• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 230000008085 renal dysfunction Effects 0.000 claims description 2
• 230000035945 sensitivity Effects 0.000 claims description 2
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
• 230000008733 trauma Effects 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• URONBCGNVPSCEO-UHFFFAOYSA-N 2-[[5-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)-3-methyl-2,6-dioxabicyclo[3.3.1]nonan-8-yl]oxy]acetic acid Chemical compound C1C(C)OC(C2)C(OCC(O)=O)COC21C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 URONBCGNVPSCEO-UHFFFAOYSA-N 0.000 claims 1
• JXPYJGCIVUUJMS-UHFFFAOYSA-N 8-(8-hydroxy-3-methyl-2,6-dioxabicyclo[3.3.1]nonan-5-yl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound C1C(C)OC(C2)C(O)COC21C1=NC(N(C(N(CCC)C2=O)=O)CCC)=C2N1 JXPYJGCIVUUJMS-UHFFFAOYSA-N 0.000 claims 1
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 1
• NVBIDTXRBMYRGD-UHFFFAOYSA-N cubane-1-carboxylic acid Chemical compound C12C3C4C5(C(=O)O)C3C2C5C41 NVBIDTXRBMYRGD-UHFFFAOYSA-N 0.000 claims 1
• 230000007812 deficiency Effects 0.000 claims 1
• 230000000241 respiratory effect Effects 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 59
• 239000002934 diuretic Substances 0.000 abstract description 8
• 230000001882 diuretic effect Effects 0.000 abstract description 5
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• 239000002598 adenosine A1 receptor antagonist Substances 0.000 abstract description 3
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• 229940124639 Selective inhibitor Drugs 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 346
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• 235000019439 ethyl acetate Nutrition 0.000 description 118
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• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 40
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