HRP940724A2 - Novel xantin derivatives having an adenosin-antagonistic activity - Google Patents

Novel xantin derivatives having an adenosin-antagonistic activity Download PDF

Info

Publication number: HRP940724A2
Authority: HR; Croatia
Prior art keywords: alkyl; group; substituted; residue; image
Prior art date: 1988-12-22

Application number

HRP-2423/89A

Other languages

English (en)

Croatian (hr)

Inventor

Ulrike Kufner-Muhl

Karl-Heinz Weber

Gerhard Walther

Werner Stransky

Helmut Ensinger

Gunter Schnignitz

Franz Josef Kuhn

Erich Lehr

Original Assignee

Boehringer Ingelheim Kg

Priority date (The priority date 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 date listed.)

1988-12-22

Filing date

1994-10-21

Publication date

1997-06-30

1994-10-21 Application filed by Boehringer Ingelheim Kg filed Critical Boehringer Ingelheim Kg

1997-06-30 Publication of HRP940724A2 publication Critical patent/HRP940724A2/hr

Links

230000000694 effects Effects 0.000 title description 6
-1 3,4-methylenedioxyphenyl Chemical group 0.000 claims abstract description 58
125000000217 alkyl group Chemical group 0.000 claims abstract description 35
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims abstract description 29
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 26
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 23
125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 12
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims abstract description 9
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 8
125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
150000003839 salts Chemical class 0.000 claims abstract description 7
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 7
229920002554 vinyl polymer Polymers 0.000 claims abstract description 7
229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 claims abstract description 6
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 5
125000005842 heteroatom Chemical group 0.000 claims abstract description 5
150000001413 amino acids Chemical class 0.000 claims abstract description 4
125000003386 piperidinyl group Chemical group 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 51
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
125000004432 carbon atom Chemical group C* 0.000 claims description 31
239000000126 substance Substances 0.000 claims description 26
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 12
238000000034 method Methods 0.000 claims description 12
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
239000013543 active substance Substances 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
229940075420 xanthine Drugs 0.000 claims description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 7
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
150000001924 cycloalkanes Chemical group 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 claims description 4
ZURRKVIQUKNLHF-UHFFFAOYSA-N 4,7,7-trimethylbicyclo[2.2.1]heptane-3-carboxylic acid Chemical group C1CC2(C)C(C(O)=O)CC1C2(C)C ZURRKVIQUKNLHF-UHFFFAOYSA-N 0.000 claims description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
239000003153 chemical reaction reagent Substances 0.000 claims description 4
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 4
125000000468 ketone group Chemical group 0.000 claims description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
125000000524 functional group Chemical group 0.000 claims description 3
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 claims description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 2
238000003747 Grignard reaction Methods 0.000 claims description 2
229930194542 Keto Natural products 0.000 claims description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
125000005336 allyloxy group Chemical group 0.000 claims description 2
125000000539 amino acid group Chemical group 0.000 claims description 2
UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
150000001925 cycloalkenes Chemical class 0.000 claims description 2
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims description 2
LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 claims description 2
150000004662 dithiols Chemical class 0.000 claims description 2
150000002240 furans Chemical class 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
229910052744 lithium Inorganic materials 0.000 claims description 2
125000000627 niacin group Chemical group 0.000 claims description 2
229960003512 nicotinic acid Drugs 0.000 claims description 2
239000011664 nicotinic acid Substances 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
239000012286 potassium permanganate Substances 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 claims 2
239000000825 pharmaceutical preparation Substances 0.000 claims 2
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 2
WWNNZCOKKKDOPX-UHFFFAOYSA-N N-methylnicotinate Chemical compound C[N+]1=CC=CC(C([O-])=O)=C1 WWNNZCOKKKDOPX-UHFFFAOYSA-N 0.000 claims 1
230000003042 antagnostic effect Effects 0.000 claims 1
229940079593 drug Drugs 0.000 claims 1
150000002118 epoxides Chemical class 0.000 claims 1
125000006384 methylpyridyl group Chemical group 0.000 claims 1
229940081066 picolinic acid Drugs 0.000 claims 1
150000004885 piperazines Chemical group 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 abstract description 6
CJVFIJXEPCVCTK-LWMBYGOMSA-N (2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C(C)C)C(C)C CJVFIJXEPCVCTK-LWMBYGOMSA-N 0.000 abstract 1
125000002252 acyl group Chemical group 0.000 abstract 1
125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
125000002947 alkylene group Chemical group 0.000 abstract 1
125000002619 bicyclic group Chemical group 0.000 abstract 1
125000001589 carboacyl group Chemical group 0.000 abstract 1
125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
125000002541 furyl group Chemical group 0.000 abstract 1
125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
230000003287 optical effect Effects 0.000 abstract 1
125000004430 oxygen atom Chemical group O* 0.000 abstract 1
125000004434 sulfur atom Chemical group 0.000 abstract 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 abstract 1
125000001544 thienyl group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 92
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000013078 crystal Substances 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
230000033228 biological regulation Effects 0.000 description 14
239000000243 solution Substances 0.000 description 14
238000003756 stirring Methods 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
150000001299 aldehydes Chemical class 0.000 description 11
239000000284 extract Substances 0.000 description 11
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
238000001816 cooling Methods 0.000 description 8
RUHGOZFOVBMWOO-UHFFFAOYSA-N 8-(3-oxocyclopentyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCC(=O)C1 RUHGOZFOVBMWOO-UHFFFAOYSA-N 0.000 description 7
229920002261 Corn starch Polymers 0.000 description 7
150000001298 alcohols Chemical class 0.000 description 7
239000008120 corn starch Substances 0.000 description 7
229940099112 cornstarch Drugs 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 7
230000009467 reduction Effects 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
150000001735 carboxylic acids Chemical class 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
NRECPLZNMXAXRH-UHFFFAOYSA-N 8-(3-hydroxycyclopentyl)-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCC(O)C1 NRECPLZNMXAXRH-UHFFFAOYSA-N 0.000 description 5
229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
238000002156 mixing Methods 0.000 description 5
238000010992 reflux Methods 0.000 description 5
WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 4
SVMBOONGPUFHRA-UHFFFAOYSA-N 5,6-diamino-1,3-dipropylpyrimidine-2,4-dione Chemical compound CCCN1C(N)=C(N)C(=O)N(CCC)C1=O SVMBOONGPUFHRA-UHFFFAOYSA-N 0.000 description 4
239000004367 Lipase Substances 0.000 description 4
102000004882 Lipase Human genes 0.000 description 4
108090001060 Lipase Proteins 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 4
239000000920 calcium hydroxide Substances 0.000 description 4
229910001861 calcium hydroxide Inorganic materials 0.000 description 4
235000011116 calcium hydroxide Nutrition 0.000 description 4
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
235000019421 lipase Nutrition 0.000 description 4
230000009935 nitrosation Effects 0.000 description 4
238000007034 nitrosation reaction Methods 0.000 description 4
239000003921 oil Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
238000006798 ring closing metathesis reaction Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
JSAVMACNWUUICZ-UHFFFAOYSA-N 5-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)furan-2-carbaldehyde Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=C(C=O)O1 JSAVMACNWUUICZ-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
241000179532 [Candida] cylindracea Species 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
239000002775 capsule Substances 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000006266 etherification reaction Methods 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
229910052736 halogen Inorganic materials 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
QCZZSANNLWPGEA-UHFFFAOYSA-N 1-(4-phenylphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=CC=C1 QCZZSANNLWPGEA-UHFFFAOYSA-N 0.000 description 2
CWKXDPPQCVWXAG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=CC(C=O)=CC=C21 CWKXDPPQCVWXAG-UHFFFAOYSA-N 0.000 description 2
XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 2
JIZRGGUCOQKGQD-UHFFFAOYSA-N 2-nitrothiophene Chemical compound [O-][N+](=O)C1=CC=CS1 JIZRGGUCOQKGQD-UHFFFAOYSA-N 0.000 description 2
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 2
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238000002636 symptomatic treatment Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
238000010998 test method Methods 0.000 description 1
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004474 valine Substances 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Pulmonology (AREA)
Hospice & Palliative Care (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Steroid Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

HRP-2423/89A 1988-12-22 1994-10-21 Novel xantin derivatives having an adenosin-antagonistic activity HRP940724A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE3843117A DE3843117A1 (de)	1988-12-22	1988-12-22	Neue xanthinderivate mit adenosin-antagonistischer wirkung
YU242389A YU47934B (sh)	1988-12-22	1989-12-20	Novi derivati ksantina sa antagonističnim dejstvom prema adenziju

Publications (1)

Publication Number	Publication Date
HRP940724A2 true HRP940724A2 (en)	1997-06-30

Family

ID=6369764

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRP-2423/89A HRP940724A2 (en)	1988-12-22	1994-10-21	Novel xantin derivatives having an adenosin-antagonistic activity

Country Status (32)

Country	Link
US (4)	US5175291A (hu)
EP (1)	EP0374808B1 (hu)
JP (1)	JP2565576B2 (hu)
KR (1)	KR0165666B1 (hu)
AT (1)	ATE136897T1 (hu)
BG (1)	BG61669B2 (hu)
BR (1)	BR1100527A (hu)
CA (1)	CA2006387C (hu)
CZ (1)	CZ286230B6 (hu)
DD (1)	DD290421A5 (hu)
DE (3)	DE8817122U1 (hu)
DK (1)	DK652689A (hu)
ES (1)	ES2086313T3 (hu)
FI (1)	FI96513C (hu)
GR (1)	GR3019733T3 (hu)
HR (1)	HRP940724A2 (hu)
HU (1)	HU218674B (hu)
IE (1)	IE74205B1 (hu)
IL (1)	IL92829A (hu)
MX (1)	MX9203618A (hu)
NO (1)	NO173502C (hu)
NZ (1)	NZ231901A (hu)
PH (2)	PH31107A (hu)
PL (1)	PL162877B1 (hu)
PT (1)	PT92658B (hu)
RU (1)	RU2057752C1 (hu)
SG (1)	SG46380A1 (hu)
SI (1)	SI8912423B (hu)
SK (1)	SK279525B6 (hu)
UA (1)	UA26427A (hu)
YU (1)	YU47934B (hu)
ZA (1)	ZA899881B (hu)

Families Citing this family (69)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE8817122U1 (de) *	1988-12-22	1993-02-04	Boehringer Ingelheim Kg, 55218 Ingelheim	Neue Xanthinderivate mit Adenosinantogenistischer Wirkung
US5290782A (en) *	1989-09-01	1994-03-01	Kyowa Hakko Kogyo Co., Ltd.	Xanthine derivatives
JPH06102662B2 (ja) *	1989-09-01	1994-12-14	協和醗酵工業株式会社	キサンチン誘導体
US5047534A (en) *	1990-03-26	1991-09-10	Merrell Dow Pharmaceuticals Inc.	Selective adenosine receptor agents
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1988
- 1988-12-22 DE DE8817122U patent/DE8817122U1/de not_active Expired - Lifetime
- 1988-12-22 DE DE3843117A patent/DE3843117A1/de not_active Ceased
1989
- 1989-12-19 CZ CS19897197A patent/CZ286230B6/cs not_active IP Right Cessation
- 1989-12-19 AT AT89123412T patent/ATE136897T1/de not_active IP Right Cessation
- 1989-12-19 DE DE58909657T patent/DE58909657D1/de not_active Expired - Fee Related
- 1989-12-19 EP EP89123412A patent/EP0374808B1/de not_active Expired - Lifetime
- 1989-12-19 SK SK7197-89A patent/SK279525B6/sk unknown
- 1989-12-19 ES ES89123412T patent/ES2086313T3/es not_active Expired - Lifetime
- 1989-12-19 SG SG1996003965A patent/SG46380A1/en unknown
- 1989-12-20 SI SI8912423A patent/SI8912423B/sl unknown
- 1989-12-20 YU YU242389A patent/YU47934B/sh unknown
- 1989-12-20 PL PL28287889A patent/PL162877B1/pl unknown
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- 1989-12-21 NO NO895168A patent/NO173502C/no not_active IP Right Cessation
- 1989-12-21 UA UA5011448A patent/UA26427A/uk unknown
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- 1989-12-21 CA CA002006387A patent/CA2006387C/en not_active Expired - Fee Related
- 1989-12-21 KR KR1019890019085A patent/KR0165666B1/ko not_active IP Right Cessation
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- 1989-12-21 IE IE414789A patent/IE74205B1/en not_active IP Right Cessation
- 1989-12-21 ZA ZA899881A patent/ZA899881B/xx unknown
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- 1989-12-21 IL IL9282989A patent/IL92829A/en active IP Right Grant
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1991
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1992
- 1992-05-07 RU SU925011448A patent/RU2057752C1/ru active
- 1992-06-26 MX MX9203618A patent/MX9203618A/es unknown
- 1992-07-10 PH PH44630A patent/PH31111A/en unknown
1993
- 1993-07-27 US US08/097,478 patent/US5532368A/en not_active Expired - Fee Related
1994
- 1994-02-08 BG BG098441A patent/BG61669B2/bg unknown
- 1994-10-21 HR HRP-2423/89A patent/HRP940724A2/hr not_active Application Discontinuation
1995
- 1995-05-30 US US08/454,452 patent/US5696124A/en not_active Expired - Fee Related
1996
- 1996-04-23 GR GR960401119T patent/GR3019733T3/el unknown
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Also Published As

Publication number	Publication date
FI96513C (fi)	1996-07-10
KR0165666B1 (ko)	1999-01-15
DE3843117A1 (de)	1990-06-28
US5532368A (en)	1996-07-02
CA2006387A1 (en)	1990-06-22
NO895168L (no)	1990-06-25
UA26427A (uk)	1999-08-30
SI8912423A (sl)	1998-04-30
CZ286230B6 (cs)	2000-02-16
SG46380A1 (en)	1998-02-20
BR1100527A (pt)	2000-08-01
PH31107A (en)	1998-02-23
DK652689A (da)	1990-06-23
ATE136897T1 (de)	1996-05-15
US5688802A (en)	1997-11-18
NO173502B (no)	1993-09-13
DE58909657D1 (de)	1996-05-23
SK719789A3 (en)	1998-12-02
PH31111A (en)	1998-02-23
PT92658A (pt)	1990-06-29
EP0374808B1 (de)	1996-04-17
SI8912423B (sl)	1998-12-31
EP0374808A3 (de)	1991-05-15
HU218674B (hu)	2000-10-28
AU4707289A (en)	1990-06-28
IE894147L (en)	1990-06-22
NZ231901A (en)	1993-12-23
NO895168D0 (no)	1989-12-21
EP0374808A2 (de)	1990-06-27
KR900009646A (ko)	1990-07-05
RU2057752C1 (ru)	1996-04-10
JPH02247180A (ja)	1990-10-02
FI96513B (fi)	1996-03-29
US5175291A (en)	1992-12-29
YU242389A (en)	1991-10-31
JP2565576B2 (ja)	1996-12-18
HUT52503A (en)	1990-07-28
NO173502C (no)	1993-12-22
IL92829A (en)	1995-12-31
YU47934B (sh)	1996-05-20
AU637990B2 (en)	1993-06-17
IE74205B1 (en)	1997-07-16
PL162877B1 (pl)	1994-01-31
HU896736D0 (en)	1990-02-28
PT92658B (pt)	1995-09-12
DD290421A5 (de)	1991-05-29
BG61669B2 (bg)	1998-02-27
ES2086313T3 (es)	1996-07-01
DE8817122U1 (de)	1993-02-04
SK279525B6 (sk)	1998-12-02
FI896117A0 (fi)	1989-12-20
DK652689D0 (da)	1989-12-21
US5696124A (en)	1997-12-09
ZA899881B (en)	1991-08-28
PL282878A1 (en)	1992-03-09
CZ719789A3 (cs)	1999-10-13
IL92829A0 (en)	1990-09-17
MX9203618A (es)	1992-09-01
CA2006387C (en)	2000-02-08
GR3019733T3 (en)	1996-07-31

Legal Events

Date	Code	Title
1997-06-30	A1OB	Publication of a patent application
1997-12-23	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2001-03-07	ODBC	Application rejected

Publication	Publication Date	Title
HRP940724A2 (en)	1997-06-30	Novel xantin derivatives having an adenosin-antagonistic activity
US5641784A (en)	1997-06-24	8-substituted 1,3-dialiphaticxanthine derivatives
US4755517A (en)	1988-07-05	Derivatives of xanthine, pharmaceutical compositions and methods of use therefor
NO161116B (no)	1989-03-28	Analogifremgangsmaate for fremstilling av antiviralt virksomme purinderivater.
CA2002834C (en)	2000-02-22	Cycloalkyl xanthines
DE60033310T2 (de)	2007-11-22	Adenosin rezeptor antagonisten sowie methoden zu deren herstellung und verwendung
US5565463A (en)	1996-10-15	9-subtituted-8-unsubstituted-9-deazaguanines
NO146775B (no)	1982-08-30	Analogifremgangsmaate ved fremstilling av terapeutisk aktive racemiske eller optisk aktive kondenserte pyrimidinderivater
CH661046A5 (fr)	1987-06-30	Derives de benzodioxinopyrrole et procedes de preparation.
JP2000501420A (ja)	2000-02-08	新規なトリアゾロプリン類、その調製方法及び医薬組成物としての使用
IL47654A (en)	1977-08-31	History 7 - Hydroxy - 4, 5, 6, 7 - Tetrahydrotiano] C - 2, 3 [- Pyridine, their preparation and spirit preparations that bluish them
FR2463142A1 (fr)	1981-02-20	Nouveaux composes de purine, leur procede de production et composition pharmaceutique les contenant