SK14282002A3 - Deriváty 8-chinolínxantínu a 8-izochinolínxantínu, farmaceutická kompozícia, ktorá ich obsahuje, ich použitie a spôsob ich prípravy - Google Patents

Deriváty 8-chinolínxantínu a 8-izochinolínxantínu, farmaceutická kompozícia, ktorá ich obsahuje, ich použitie a spôsob ich prípravy Download PDF

Info

Publication number: SK14282002A3
Authority: SK; Slovakia
Prior art keywords: group; alkyl; alkoxy; hydrogen; ring
Prior art date: 2000-04-07

Application number

SK1428-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Gurdip Bhalay

Stephen Paul Collingwood

Robin Alec Fairhurst

Sylvie Felicite Gomez

Reto Naef

David Andrew Sandham

Original Assignee

Novartis Ag

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.)

2000-04-07

Filing date

2001-04-05

Publication date

2003-04-01

2001-04-05 Application filed by Novartis Ag filed Critical Novartis Ag

2003-04-01 Publication of SK14282002A3 publication Critical patent/SK14282002A3/sk

Links

238000000034 method Methods 0.000 title description 100
238000002360 preparation method Methods 0.000 title description 16
239000008194 pharmaceutical composition Substances 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 112
-1 hydroxy, aminosulfonyl Chemical group 0.000 claims abstract description 84
125000000217 alkyl group Chemical group 0.000 claims abstract description 79
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 51
239000001257 hydrogen Substances 0.000 claims abstract description 50
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 37
150000003839 salts Chemical group 0.000 claims abstract description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 30
229910052736 halogen Inorganic materials 0.000 claims abstract description 27
150000002367 halogens Chemical class 0.000 claims abstract description 27
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
125000001424 substituent group Chemical group 0.000 claims abstract description 27
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 26
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 24
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 21
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 20
125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 18
125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 17
125000003118 aryl group Chemical group 0.000 claims abstract description 16
229910052799 carbon Inorganic materials 0.000 claims abstract description 15
150000002431 hydrogen Chemical class 0.000 claims abstract description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 13
125000002252 acyl group Chemical group 0.000 claims abstract description 12
125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 11
125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 11
125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 7
125000004415 heterocyclylalkyl group Chemical group 0.000 claims abstract description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000004442 acylamino group Chemical group 0.000 claims abstract description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
125000006413 ring segment Chemical group 0.000 claims abstract description 6
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims abstract description 5
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 5
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 4
125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 claims abstract description 4
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims abstract description 3
125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims abstract description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 24
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 21
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 3
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
125000003884 phenylalkyl group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
239000000543 intermediate Substances 0.000 description 108
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
238000006243 chemical reaction Methods 0.000 description 68
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 67
239000000243 solution Substances 0.000 description 66
239000011541 reaction mixture Substances 0.000 description 64
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 38
239000002904 solvent Substances 0.000 description 31
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
239000007787 solid Substances 0.000 description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
239000002253 acid Substances 0.000 description 21
239000003960 organic solvent Substances 0.000 description 21
239000000725 suspension Substances 0.000 description 20
238000003818 flash chromatography Methods 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
238000001704 evaporation Methods 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000012267 brine Substances 0.000 description 15
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
125000003226 pyrazolyl group Chemical group 0.000 description 14
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
230000008569 process Effects 0.000 description 12
239000000047 product Substances 0.000 description 12
239000002585 base Substances 0.000 description 11
239000012043 crude product Substances 0.000 description 11
101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 10
101150098694 PDE5A gene Proteins 0.000 description 10
238000009835 boiling Methods 0.000 description 10
102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 10
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
229910000041 hydrogen chloride Inorganic materials 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
238000010992 reflux Methods 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
238000000746 purification Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000003125 aqueous solvent Substances 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 7
150000004702 methyl esters Chemical class 0.000 description 7
150000007530 organic bases Chemical class 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
238000005406 washing Methods 0.000 description 7
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 6
VULNACCPMCVPGE-UHFFFAOYSA-N 5,6-diamino-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(N)=C(N)C(=O)N(C)C1=O VULNACCPMCVPGE-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
150000001721 carbon Chemical group 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
150000007529 inorganic bases Chemical class 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
230000017074 necrotic cell death Effects 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
238000002953 preparative HPLC Methods 0.000 description 6
BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 6
229940075420 xanthine Drugs 0.000 description 6
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 5
208000010228 Erectile Dysfunction Diseases 0.000 description 5
201000001880 Sexual dysfunction Diseases 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
150000008044 alkali metal hydroxides Chemical class 0.000 description 5
238000001035 drying Methods 0.000 description 5
125000004494 ethyl ester group Chemical group 0.000 description 5
238000000605 extraction Methods 0.000 description 5
238000001914 filtration Methods 0.000 description 5
201000001881 impotence Diseases 0.000 description 5
231100000872 sexual dysfunction Toxicity 0.000 description 5
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 4
QHDVBZROTMPMAP-UHFFFAOYSA-N 2-(1-chloro-6,7-dimethoxyisoquinolin-4-yl)acetic acid Chemical compound N1=CC(CC(O)=O)=C2C=C(OC)C(OC)=CC2=C1Cl QHDVBZROTMPMAP-UHFFFAOYSA-N 0.000 description 4
XCJMMVCKDPLZPO-UHFFFAOYSA-N 2-(5-chloro-6-methoxyisoquinolin-4-yl)acetic acid Chemical compound C1=NC=C(CC(O)=O)C2=C(Cl)C(OC)=CC=C21 XCJMMVCKDPLZPO-UHFFFAOYSA-N 0.000 description 4
DSUWAPZUHADAER-UHFFFAOYSA-N 2-(6-methoxyisoquinolin-4-yl)acetic acid Chemical compound C1=NC=C(CC(O)=O)C2=CC(OC)=CC=C21 DSUWAPZUHADAER-UHFFFAOYSA-N 0.000 description 4
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 4
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000001301 oxygen Chemical group 0.000 description 4
125000000168 pyrrolyl group Chemical group 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
238000003756 stirring Methods 0.000 description 4
229910052717 sulfur Chemical group 0.000 description 4
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
101150065749 Churc1 gene Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 3
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
230000027455 binding Effects 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
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239000011550 stock solution Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
230000006103 sulfonylation Effects 0.000 description 1
238000005694 sulfonylation reaction Methods 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical group C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
231100000886 tinnitus Toxicity 0.000 description 1
238000004448 titration Methods 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229940035893 uracil Drugs 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
230000002792 vascular Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
125000005023 xylyl group Chemical group 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1

Classifications

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- C—CHEMISTRY; METALLURGY
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- 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

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Pulmonology (AREA)
Endocrinology (AREA)
Ophthalmology & Optometry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Dermatology (AREA)
Gynecology & Obstetrics (AREA)
Hospice & Palliative Care (AREA)
Nutrition Science (AREA)
Vascular Medicine (AREA)
Oncology (AREA)
Psychiatry (AREA)
Pregnancy & Childbirth (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

SK1428-2002A 2000-04-07 2001-04-05 Deriváty 8-chinolínxantínu a 8-izochinolínxantínu, farmaceutická kompozícia, ktorá ich obsahuje, ich použitie a spôsob ich prípravy SK14282002A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0008694.2A GB0008694D0 (en)	2000-04-07	2000-04-07	Organic compounds
PCT/EP2001/003909 WO2001077110A1 (en)	2000-04-07	2001-04-05	8-quinolinxanthine and 8-isoquinolinxanthine derivatives as pde 5 inhibitors

Publications (1)

Publication Number	Publication Date
SK14282002A3 true SK14282002A3 (sk)	2003-04-01

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ID=9889516

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1428-2002A SK14282002A3 (sk)	2000-04-07	2001-04-05	Deriváty 8-chinolínxantínu a 8-izochinolínxantínu, farmaceutická kompozícia, ktorá ich obsahuje, ich použitie a spôsob ich prípravy

Country Status (29)

Country	Link
US (1)	US20030171384A1 (pt)
EP (1)	EP1268480B1 (pt)
JP (1)	JP3869725B2 (pt)
KR (1)	KR100526094B1 (pt)
CN (1)	CN1176922C (pt)
AR (1)	AR028531A1 (pt)
AT (1)	ATE253576T1 (pt)
AU (2)	AU7392101A (pt)
BR (1)	BR0109855A (pt)
CA (1)	CA2403514C (pt)
CZ (1)	CZ20023305A3 (pt)
DE (1)	DE60101158T2 (pt)
DK (1)	DK1268480T3 (pt)
ES (1)	ES2210169T3 (pt)
GB (1)	GB0008694D0 (pt)
HU (1)	HUP0300565A3 (pt)
IL (1)	IL152078A0 (pt)
MX (1)	MXPA02009903A (pt)
MY (1)	MY119238A (pt)
NO (1)	NO20024741L (pt)
NZ (1)	NZ521361A (pt)
PE (1)	PE20020228A1 (pt)
PL (1)	PL212407B1 (pt)
PT (1)	PT1268480E (pt)
RU (1)	RU2269529C2 (pt)
SK (1)	SK14282002A3 (pt)
TR (1)	TR200400185T4 (pt)
WO (1)	WO2001077110A1 (pt)
ZA (1)	ZA200207956B (pt)

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GB9301192D0 (en) *	1993-06-09	1993-06-09	Trott Francis W	Flower shaped mechanised table
AU4501199A (en) *	1998-06-03	1999-12-20	Almirall Prodesfarma S.A.	8-phenylxanthine derivatives and their use as phosphodiesterase inhibitors
GB9828340D0 (en) *	1998-12-22	1999-02-17	Novartis Ag	Organic compounds

2000
- 2000-04-07 GB GBGB0008694.2A patent/GB0008694D0/en not_active Ceased
2001
- 2001-04-05 ES ES01940294T patent/ES2210169T3/es not_active Expired - Lifetime
- 2001-04-05 PT PT01940294T patent/PT1268480E/pt unknown
- 2001-04-05 SK SK1428-2002A patent/SK14282002A3/sk unknown
- 2001-04-05 WO PCT/EP2001/003909 patent/WO2001077110A1/en not_active Ceased
- 2001-04-05 CZ CZ20023305A patent/CZ20023305A3/cs unknown
- 2001-04-05 DE DE60101158T patent/DE60101158T2/de not_active Expired - Lifetime
- 2001-04-05 DK DK01940294T patent/DK1268480T3/da active
- 2001-04-05 AU AU7392101A patent/AU7392101A/xx active Pending
- 2001-04-05 JP JP2001575583A patent/JP3869725B2/ja not_active Expired - Fee Related
- 2001-04-05 EP EP01940294A patent/EP1268480B1/en not_active Expired - Lifetime
- 2001-04-05 IL IL15207801A patent/IL152078A0/xx unknown
- 2001-04-05 BR BR0109855-1A patent/BR0109855A/pt not_active IP Right Cessation
- 2001-04-05 KR KR10-2002-7012627A patent/KR100526094B1/ko not_active Expired - Fee Related
- 2001-04-05 AT AT01940294T patent/ATE253576T1/de active
- 2001-04-05 MX MXPA02009903A patent/MXPA02009903A/es active IP Right Grant
- 2001-04-05 CN CNB018074898A patent/CN1176922C/zh not_active Expired - Fee Related
- 2001-04-05 AU AU2001273921A patent/AU2001273921B2/en not_active Ceased
- 2001-04-05 PL PL358205A patent/PL212407B1/pl unknown
- 2001-04-05 PE PE2001000317A patent/PE20020228A1/es not_active Application Discontinuation
- 2001-04-05 AR ARP010101623A patent/AR028531A1/es not_active Application Discontinuation
- 2001-04-05 RU RU2002129557/04A patent/RU2269529C2/ru not_active IP Right Cessation
- 2001-04-05 MY MYPI20011632A patent/MY119238A/en unknown
- 2001-04-05 US US10/240,481 patent/US20030171384A1/en not_active Abandoned
- 2001-04-05 HU HU0300565A patent/HUP0300565A3/hu unknown
- 2001-04-05 TR TR2004/00185T patent/TR200400185T4/xx unknown
- 2001-04-05 CA CA002403514A patent/CA2403514C/en not_active Expired - Fee Related
- 2001-04-05 NZ NZ521361A patent/NZ521361A/en unknown
2002
- 2002-10-02 NO NO20024741A patent/NO20024741L/no not_active Application Discontinuation
- 2002-10-03 ZA ZA200207956A patent/ZA200207956B/en unknown

Also Published As

Publication number	Publication date
EP1268480A1 (en)	2003-01-02
AU7392101A (en)	2001-10-23
JP3869725B2 (ja)	2007-01-17
NZ521361A (en)	2004-05-28
NO20024741D0 (no)	2002-10-02
CN1420887A (zh)	2003-05-28
HUP0300565A3 (en)	2004-10-28
RU2002129557A (ru)	2004-03-27
DE60101158D1 (en)	2003-12-11
EP1268480B1 (en)	2003-11-05
WO2001077110A1 (en)	2001-10-18
CA2403514A1 (en)	2001-10-18
CA2403514C (en)	2010-01-12
ATE253576T1 (de)	2003-11-15
PT1268480E (pt)	2004-03-31
AU2001273921B2 (en)	2005-05-05
ES2210169T3 (es)	2004-07-01
US20030171384A1 (en)	2003-09-11
NO20024741L (no)	2002-10-02
HUP0300565A2 (hu)	2003-07-28
MY119238A (en)	2005-04-30
DE60101158T2 (de)	2004-08-26
IL152078A0 (en)	2003-05-29
CN1176922C (zh)	2004-11-24
AR028531A1 (es)	2003-05-14
GB0008694D0 (en)	2000-05-31
JP2003530398A (ja)	2003-10-14
ZA200207956B (en)	2003-07-16
PL212407B1 (pl)	2012-09-28
DK1268480T3 (da)	2004-03-15
RU2269529C2 (ru)	2006-02-10
TR200400185T4 (tr)	2004-03-22
PL358205A1 (en)	2004-08-09
KR100526094B1 (ko)	2005-11-08
PE20020228A1 (es)	2002-03-28
BR0109855A (pt)	2003-06-03
MXPA02009903A (es)	2003-03-27
CZ20023305A3 (cs)	2003-01-15
KR20020081590A (ko)	2002-10-28

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