HRP960009A2 - 9-substituted 2-(2-n-alkoxyphenyl)-purin-6-ones - Google Patents

9-substituted 2-(2-n-alkoxyphenyl)-purin-6-ones Download PDF

Info

Publication number: HRP960009A2
Authority: HR; Croatia
Prior art keywords: straight; chain; carbon atoms; substituted; branched alkyl
Prior art date: 1995-01-19

Application number

HR19501480.4A

Other languages

English (en)

Croatian (hr)

Inventor

Matthias Schramm

Original Assignee

Matthias Schramm

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.)

1995-01-19

Filing date

1996-01-08

Publication date

1997-12-31

1996-01-08 Application filed by Matthias Schramm filed Critical Matthias Schramm

1997-12-31 Publication of HRP960009A2 publication Critical patent/HRP960009A2/hr

Links

125000004432 carbon atom Chemical group C* 0.000 claims description 107
125000000217 alkyl group Chemical group 0.000 claims description 102
229910052739 hydrogen Inorganic materials 0.000 claims description 79
239000001257 hydrogen Substances 0.000 claims description 79
150000001875 compounds Chemical class 0.000 claims description 50
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
150000002431 hydrogen Chemical class 0.000 claims description 34
238000000034 method Methods 0.000 claims description 32
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
-1 sulfonic acid chlorides Chemical class 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 12
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
229940079593 drug Drugs 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
239000000460 chlorine Chemical group 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
239000012442 inert solvent Substances 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
208000001435 Thromboembolism Diseases 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
206010061218 Inflammation Diseases 0.000 claims description 3
230000010933 acylation Effects 0.000 claims description 3
238000005917 acylation reaction Methods 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
238000005576 amination reaction Methods 0.000 claims description 2
150000001540 azides Chemical group 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical group 0.000 claims description 2
201000001881 impotence Diseases 0.000 claims description 2
230000003647 oxidation Effects 0.000 claims description 2
238000007254 oxidation reaction Methods 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 109
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 32
239000002904 solvent Substances 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 17
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
239000007832 Na2SO4 Substances 0.000 description 13
239000012074 organic phase Substances 0.000 description 13
239000002585 base Substances 0.000 description 12
239000000203 mixture Substances 0.000 description 12
229910001868 water Inorganic materials 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
239000000243 solution Substances 0.000 description 10
238000001035 drying Methods 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000003480 eluent Substances 0.000 description 8
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
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 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
DVNYTAVYBRSTGK-UHFFFAOYSA-N 5-aminoimidazole-4-carboxamide Chemical class NC(=O)C=1N=CNC=1N DVNYTAVYBRSTGK-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
239000002253 acid Substances 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
230000033228 biological regulation Effects 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
150000002170 ethers Chemical class 0.000 description 5
229940052303 ethers for general anesthesia Drugs 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012071 phase Substances 0.000 description 4
DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical group CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
QAXDVKBGZRMSHF-UHFFFAOYSA-N 6-acetyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(C)=O QAXDVKBGZRMSHF-UHFFFAOYSA-N 0.000 description 3
TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
230000003110 anti-inflammatory effect Effects 0.000 description 3
210000000709 aorta Anatomy 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229960004132 diethyl ether Drugs 0.000 description 3
238000009472 formulation Methods 0.000 description 3
150000002440 hydroxy compounds Chemical class 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
UFZNZKGKBWOSJG-UHFFFAOYSA-N purin-2-one Chemical class O=C1N=CC2=NC=NC2=N1 UFZNZKGKBWOSJG-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
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 description 2
102000002723 Atrial Natriuretic Factor Human genes 0.000 description 2
101800001288 Atrial natriuretic factor Proteins 0.000 description 2
101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 2
102000000584 Calmodulin Human genes 0.000 description 2
108010041952 Calmodulin Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
108010044467 Isoenzymes Proteins 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
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239000012346 acetyl chloride Substances 0.000 description 2
239000013543 active substance Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
238000002399 angioplasty Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
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229950005499 carbon tetrachloride Drugs 0.000 description 2
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NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
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238000002156 mixing Methods 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
125000005936 piperidyl group Chemical group 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
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VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
210000002229 urogenital system Anatomy 0.000 description 2
238000005292 vacuum distillation Methods 0.000 description 2
230000000304 vasodilatating effect Effects 0.000 description 2
239000008096 xylene Substances 0.000 description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 1
FSQHJEDHYSCBCW-UHFFFAOYSA-N 2-(2-propoxyphenyl)purin-6-one Chemical compound CCCOC1=CC=CC=C1C1=NC(=O)C2=NC=NC2=N1 FSQHJEDHYSCBCW-UHFFFAOYSA-N 0.000 description 1
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LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
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229910001863 barium hydroxide Inorganic materials 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
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CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
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238000009835 boiling Methods 0.000 description 1
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239000000969 carrier Substances 0.000 description 1
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238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
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238000007887 coronary angioplasty Methods 0.000 description 1
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239000012973 diazabicyclooctane Substances 0.000 description 1
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239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
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208000010125 myocardial infarction Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000006187 pill Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
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238000010992 reflux Methods 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
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238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
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208000017520 skin disease Diseases 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
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238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
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238000002560 therapeutic procedure Methods 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (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)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

HR19501480.4A 1995-01-19 1996-01-08 9-substituted 2-(2-n-alkoxyphenyl)-purin-6-ones HRP960009A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19501480A DE19501480A1 (de)	1995-01-19	1995-01-19	9-substituierte 2-(2-n-Alkoxyphenyl)-purin-6-one

Publications (1)

Publication Number	Publication Date
HRP960009A2 true HRP960009A2 (en)	1997-12-31

Family

ID=7751828

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR19501480.4A HRP960009A2 (en)	1995-01-19	1996-01-08	9-substituted 2-(2-n-alkoxyphenyl)-purin-6-ones

Country Status (30)

Country	Link
US (1)	US5866571A (cs)
EP (1)	EP0722943A1 (cs)
JP (1)	JPH08231546A (cs)
KR (1)	KR960029335A (cs)
CN (1)	CN1138583A (cs)
AR (1)	AR002704A1 (cs)
AU (1)	AU4097796A (cs)
BG (1)	BG61729B1 (cs)
BR (1)	BR9600149A (cs)
CA (1)	CA2167349A1 (cs)
CO (1)	CO4700524A1 (cs)
CZ (1)	CZ16896A3 (cs)
DE (1)	DE19501480A1 (cs)
EE (1)	EE9600020A (cs)
FI (1)	FI960226A7 (cs)
HR (1)	HRP960009A2 (cs)
HU (1)	HUP9600107A3 (cs)
IL (1)	IL116771A (cs)
MA (1)	MA23779A1 (cs)
NO (1)	NO960221L (cs)
NZ (1)	NZ280829A (cs)
PE (1)	PE10597A1 (cs)
PL (1)	PL312353A1 (cs)
SG (1)	SG47379A1 (cs)
SK (1)	SK7696A3 (cs)
SV (1)	SV1996000004A (cs)
TN (1)	TNSN96005A1 (cs)
TR (1)	TR199600701A2 (cs)
YU (1)	YU2896A (cs)
ZA (1)	ZA96399B (cs)

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US6064072A (en) *	1997-05-12	2000-05-16	Cymer, Inc.	Plasma focus high energy photon source
DE19838300A1 (de) *	1998-08-24	2000-03-02	Bayer Ag	9-Dialkylaminopurinon-derivate
US6124303A (en) *	1998-09-11	2000-09-26	Cell Pathways, Inc.	Method for inhibiting neoplastic cells and related conditions by exposure to 9-substituted 2-(2-N-aloxyphenyl) purin-6-ones
US6268372B1 (en)	1998-09-11	2001-07-31	Cell Pathways, Inc.	Method for inhibiting neoplastic cells and related conditions by exposure to 2,9-disubstituted purin-6-ones
GB9924020D0 (en) *	1999-10-11	1999-12-15	Pfizer Ltd	Pharmaceutically active compounds
AUPQ515700A0 (en) *	2000-01-19	2000-02-10	Fujisawa Pharmaceutical Co., Ltd.	Imidazole compounds
CN1264574C (zh) *	2000-09-06	2006-07-19	田边制药株式会社	口服制剂
NZ527585A (en) *	2001-02-15	2005-04-29	Tanabe Seiyaku Co	Tablets quickly disintegrated in oral cavity
US6479493B1 (en)	2001-08-23	2002-11-12	Cell Pathways, Inc.	Methods for treatment of type I diabetes
HU228316B1 (en) *	2001-12-13	2013-03-28	Daiichi Sankyo Company	Pyrazolopyrimidinone derivatives having pde7-inhibitory activity
US6962940B2 (en)	2002-03-20	2005-11-08	Celgene Corporation	(+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof
US7276529B2 (en)	2002-03-20	2007-10-02	Celgene Corporation	Methods of the treatment or prevention of exercise-induced asthma using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
US7893101B2 (en)	2002-03-20	2011-02-22	Celgene Corporation	Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof
US7208516B2 (en)	2002-03-20	2007-04-24	Celgene Corporation	Methods of the treatment of psoriatic arthritis using (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
US20050154202A1 (en) *	2002-04-05	2005-07-14	Hagmann William K.	Substituted aryl amides
MX2016014384A (es)	2014-06-23	2017-01-20	Celgene Corp	Apremilast para el tratamiento de una enfermedad del higado o una anormalidad en la funcion del higado.

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Publication number	Priority date	Publication date	Assignee	Title
US4451478A (en) *	1982-03-12	1984-05-29	Newport Pharmaceuticals International, Inc.	Imidazole compounds
CA1303037C (en) *	1987-02-02	1992-06-09	Smith Kline & French Laboratories Limited	Purinone derivatives as bronchodilators vasodilators and anti-allergic agents
GB8817651D0 (en) *	1988-07-25	1988-09-01	Smith Kline French Lab	Chemical compounds
GB9126260D0 (en) *	1991-12-11	1992-02-12	Pfizer Ltd	Therapeutic agents
US5294612A (en) *	1992-03-30	1994-03-15	Sterling Winthrop Inc.	6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof
US5734053A (en) *	1992-06-26	1998-03-31	Pfizer Inc	Purinone antianginal agents
GB9213623D0 (en) *	1992-06-26	1992-08-12	Pfizer Ltd	Therapeutic agents

1995
- 1995-01-19 DE DE19501480A patent/DE19501480A1/de not_active Withdrawn
1996
- 1996-01-08 EP EP96100153A patent/EP0722943A1/de not_active Withdrawn
- 1996-01-08 HR HR19501480.4A patent/HRP960009A2/hr not_active Application Discontinuation
- 1996-01-12 TR TR96/00023A patent/TR199600701A2/xx unknown
- 1996-01-15 AU AU40977/96A patent/AU4097796A/en not_active Abandoned
- 1996-01-16 IL IL11677196A patent/IL116771A/xx not_active IP Right Cessation
- 1996-01-16 NZ NZ280829A patent/NZ280829A/en unknown
- 1996-01-16 US US08/585,996 patent/US5866571A/en not_active Expired - Fee Related
- 1996-01-16 CA CA002167349A patent/CA2167349A1/en not_active Abandoned
- 1996-01-17 FI FI960226A patent/FI960226A7/fi unknown
- 1996-01-17 TN TNTNSN96005A patent/TNSN96005A1/fr unknown
- 1996-01-17 PL PL96312353A patent/PL312353A1/xx unknown
- 1996-01-17 SG SG1996000262A patent/SG47379A1/en unknown
- 1996-01-18 ZA ZA96399A patent/ZA96399B/xx unknown
- 1996-01-18 HU HU9600107A patent/HUP9600107A3/hu unknown
- 1996-01-18 CZ CZ96168A patent/CZ16896A3/cs unknown
- 1996-01-18 BG BG100291A patent/BG61729B1/bg unknown
- 1996-01-18 JP JP8023474A patent/JPH08231546A/ja active Pending
- 1996-01-18 MA MA24134A patent/MA23779A1/fr unknown
- 1996-01-18 EE EE9600020A patent/EE9600020A/xx unknown
- 1996-01-18 YU YU2896A patent/YU2896A/sh unknown
- 1996-01-18 SK SK76-96A patent/SK7696A3/sk unknown
- 1996-01-18 KR KR1019960001003A patent/KR960029335A/ko not_active Withdrawn
- 1996-01-18 NO NO960221A patent/NO960221L/no unknown
- 1996-01-18 BR BR9600149A patent/BR9600149A/pt active Search and Examination
- 1996-01-19 CN CN96101805A patent/CN1138583A/zh active Pending
- 1996-01-19 SV SV1996000004A patent/SV1996000004A/es unknown
- 1996-01-19 AR ARP960101086A patent/AR002704A1/es unknown
- 1996-01-19 PE PE1996000045A patent/PE10597A1/es not_active Application Discontinuation
- 1996-01-19 CO CO96002170A patent/CO4700524A1/es unknown

Also Published As

Publication number	Publication date
US5866571A (en)	1999-02-02
EE9600020A (et)	1996-08-15
BG100291A (bg)	1996-07-31
TR199600701A2 (tr)	1996-08-21
YU2896A (sh)	1999-03-04
FI960226A7 (fi)	1996-07-20
HUP9600107A2 (en)	1997-05-28
NO960221D0 (no)	1996-01-18
CO4700524A1 (es)	1998-12-29
FI960226A0 (fi)	1996-01-17
SK7696A3 (en)	1996-08-07
PE10597A1 (es)	1997-06-13
IL116771A0 (en)	1996-05-14
CZ16896A3 (en)	1996-08-14
HU9600107D0 (en)	1996-03-28
BG61729B1 (bg)	1998-04-30
IL116771A (en)	1999-06-20
PL312353A1 (en)	1996-07-22
HUP9600107A3 (en)	1999-06-28
AU4097796A (en)	1996-07-25
SG47379A1 (en)	1998-04-17
EP0722943A1 (de)	1996-07-24
MA23779A1 (fr)	1996-10-01
CA2167349A1 (en)	1996-07-20
DE19501480A1 (de)	1996-07-25
CN1138583A (zh)	1996-12-25
AR002704A1 (es)	1998-04-29
ZA96399B (en)	1996-08-14
KR960029335A (ko)	1996-08-17
TNSN96005A1 (en)	2005-03-15
SV1996000004A (es)	1997-02-19
BR9600149A (pt)	1998-01-06
NZ280829A (en)	1998-04-27
NO960221L (no)	1996-07-22
JPH08231546A (ja)	1996-09-10

Legal Events

Date	Code	Title
1997-12-31	A1OB	Publication of a patent application
1998-03-16	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
1999-05-10	OBST	Application withdrawn

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