DD283402A5 - Verfahren zur herstellung von 2-substituierten adenosinderivaten - Google Patents

Verfahren zur herstellung von 2-substituierten adenosinderivaten Download PDF

Info

Publication number: DD283402A5
Authority: DD; German Democratic Republic
Prior art keywords: group; lower alkyl; hydrogen; groups; pharmaceutically acceptable
Prior art date: 1988-01-07

Application number

DD89324859A

Other languages

German (de)

English (en)

Inventor

Alan J Hutchison

John E Francis

Original Assignee

��`��@��k��

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.)

1988-01-07

Filing date

1989-01-05

Publication date

1990-10-10

1989-01-05 Application filed by ��`��@��k�� filed Critical ��`��@��k��

1990-10-10 Publication of DD283402A5 publication Critical patent/DD283402A5/de

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-1 2-SUBSTITUTED ADENOSINE Chemical class 0.000 title claims abstract description 106
238000000034 method Methods 0.000 title claims abstract description 53
238000002360 preparation method Methods 0.000 title claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 266
239000001257 hydrogen Substances 0.000 claims description 227
229910052739 hydrogen Inorganic materials 0.000 claims description 227
150000001875 compounds Chemical class 0.000 claims description 128
150000002148 esters Chemical class 0.000 claims description 118
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 110
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 98
239000002126 C01EB10 - Adenosine Substances 0.000 claims description 94
229960005305 adenosine Drugs 0.000 claims description 94
150000003839 salts Chemical class 0.000 claims description 83
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 79
150000002431 hydrogen Chemical class 0.000 claims description 74
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 74
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 68
125000002947 alkylene group Chemical group 0.000 claims description 63
229910052736 halogen Inorganic materials 0.000 claims description 58
239000000203 mixture Substances 0.000 claims description 58
125000003545 alkoxy group Chemical group 0.000 claims description 57
150000002367 halogens Chemical class 0.000 claims description 55
125000001424 substituent group Chemical group 0.000 claims description 48
239000002243 precursor Substances 0.000 claims description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
239000000651 prodrug Substances 0.000 claims description 33
229940002612 prodrug Drugs 0.000 claims description 33
125000004423 acyloxy group Chemical group 0.000 claims description 29
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 26
150000001412 amines Chemical class 0.000 claims description 25
125000004432 carbon atom Chemical group C* 0.000 claims description 23
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
125000004450 alkenylene group Chemical group 0.000 claims description 19
150000001408 amides Chemical class 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000004076 pyridyl group Chemical group 0.000 claims description 12
125000004149 thio group Chemical group *S* 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
238000006243 chemical reaction Methods 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000000168 pyrrolyl group Chemical group 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 9
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
229940079593 drug Drugs 0.000 claims description 6
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
QYCGBAJADAGLLK-UHFFFAOYSA-N 1-(cyclohepten-1-yl)cycloheptene Chemical group C1CCCCC=C1C1=CCCCCC1 QYCGBAJADAGLLK-UHFFFAOYSA-N 0.000 claims description 5
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 3
XGIMEDAMLNPVHR-QIFOKDCASA-N (2r,3r,4s,5r)-2-[6-amino-2-[(2-hydroxy-2-phenylethyl)amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NCC(O)C1=CC=CC=C1 XGIMEDAMLNPVHR-QIFOKDCASA-N 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
230000002452 interceptive effect Effects 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 claims 3
102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
150000003835 adenosine derivatives Chemical class 0.000 claims 1
125000002355 alkine group Chemical group 0.000 claims 1
229940030600 antihypertensive agent Drugs 0.000 claims 1
239000002220 antihypertensive agent Substances 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 claims 1
239000010985 leather Substances 0.000 claims 1
125000005981 pentynyl group Chemical group 0.000 claims 1
239000000556 agonist Substances 0.000 abstract description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 95
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 88
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 48
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 43
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
239000007858 starting material Substances 0.000 description 32
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
239000002253 acid Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
239000002904 solvent Substances 0.000 description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
239000003921 oil Substances 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000003480 eluent Substances 0.000 description 16
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
150000007513 acids Chemical class 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 12
239000007787 solid Substances 0.000 description 12
241000124008 Mammalia Species 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
239000000725 suspension Substances 0.000 description 11
239000000543 intermediate Substances 0.000 description 10
BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 description 9
239000003610 charcoal Substances 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
201000010099 disease Diseases 0.000 description 8
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000011282 treatment Methods 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
239000012259 ether extract Substances 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
PBCITPUKHNCINI-UHFFFAOYSA-N 2-(4-bromothiophen-2-yl)ethanamine Chemical compound NCCC1=CC(Br)=CS1 PBCITPUKHNCINI-UHFFFAOYSA-N 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 5
102100025358 Probable G-protein coupled receptor 162 Human genes 0.000 description 5
208000007536 Thrombosis Diseases 0.000 description 5
239000002024 ethyl acetate extract Substances 0.000 description 5
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000008107 starch Substances 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
239000000284 extract Substances 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000009870 specific binding Effects 0.000 description 4
239000000126 substance Substances 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
239000005711 Benzoic acid Substances 0.000 description 3
241000700159 Rattus Species 0.000 description 3
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
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235000010233 benzoic acid Nutrition 0.000 description 3
230000027455 binding Effects 0.000 description 3
230000036772 blood pressure Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
210000000748 cardiovascular system Anatomy 0.000 description 3
239000000969 carrier Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
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235000010446 mineral oil Nutrition 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 3
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239000002244 precipitate Substances 0.000 description 3
239000011734 sodium Substances 0.000 description 3
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238000011699 spontaneously hypertensive rat Methods 0.000 description 3
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DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 2
DBFQHWKOYLSNEU-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2-phenylethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NCCC1=CC=CC=C1 DBFQHWKOYLSNEU-LSCFUAHRSA-N 0.000 description 2
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125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
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HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
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CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
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ULSIYEODSMZIPX-UHFFFAOYSA-N phenylethanolamine Chemical compound NCC(O)C1=CC=CC=C1 ULSIYEODSMZIPX-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
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229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
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125000006410 propenylene group Chemical group 0.000 description 1
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238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
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238000007086 side reaction Methods 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
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239000000600 sorbitol Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
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239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
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PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
235000021286 stilbenes Nutrition 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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 description 1
238000003828 vacuum filtration Methods 0.000 description 1
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125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical class [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/173—Purine radicals with 2-deoxyribosyl as the saccharide radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- A61P9/12—Antihypertensives

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biotechnology (AREA)
Pharmacology & Pharmacy (AREA)
Genetics & Genomics (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Hematology (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

DD89324859A 1988-01-07 1989-01-05 Verfahren zur herstellung von 2-substituierten adenosinderivaten DD283402A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US14205588A	1988-01-07	1988-01-07
US07/193,968 US5034381A (en)	1988-01-07	1988-05-13	2-(substituted amino) adenosines as antihypertensives

Publications (1)

Publication Number	Publication Date
DD283402A5 true DD283402A5 (de)	1990-10-10

Family

ID=26839719

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD89324859A DD283402A5 (de)	1988-01-07	1989-01-05	Verfahren zur herstellung von 2-substituierten adenosinderivaten

Country Status (17)

Country	Link
US (1)	US5034381A (da)
EP (1)	EP0323807A3 (da)
JP (1)	JPH01265100A (da)
KR (1)	KR890011903A (da)
AU (1)	AU618055B2 (da)
CA (1)	CA1325209C (da)
DD (1)	DD283402A5 (da)
DK (1)	DK5089A (da)
FI (1)	FI90430C (da)
HU (1)	HU202550B (da)
IL (1)	IL88877A0 (da)
MX (1)	MX14446A (da)
NO (1)	NO169843C (da)
NZ (1)	NZ227542A (da)
PH (1)	PH26672A (da)
PT (1)	PT89392B (da)
ZA (1)	ZA8984B (da)

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US4977144A (en) *	1988-08-02	1990-12-11	Ciba-Geigy Corporation	Imidazo[4,5-b]pyridine derivatives as cardiovascular agents
US5189027A (en)	1990-11-30	1993-02-23	Yamasa Shoyu Kabushiki Kaisha	2-substituted adenosine derivatives and pharmaceutical compositions for circulatory diseases
US5206222A (en) *	1991-05-22	1993-04-27	Vanderbilt University	Methods for the reduction of myocardial reperfusion injury
IT1254915B (it) *	1992-04-24	1995-10-11	Gloria Cristalli	Derivati di adenosina ad attivita' a2 agonista
US5426101A (en) *	1992-09-30	1995-06-20	Merrell Dow Pharmaceuticals Inc.	2-substituted adenosines with A-2 receptor affinity
IL107101A0 (en) *	1992-09-30	1993-12-28	Merrell Dow Pharma	2-substituted adenosines with a-2 receptor affinity
WO1994023723A1 (en) *	1993-04-15	1994-10-27	New York University	Adenosine receptor agonists for the promotion of wound healing
US5817641A (en) *	1994-07-21	1998-10-06	Thomas Jefferson University	Treatment of enterotoxigenic diarrhea with 2-substituted adenosine derivatives
AU740770B2 (en)	1997-06-18	2001-11-15	Aderis Pharmaceuticals, Inc.	Compositions and methods for preventing restenosis following revascularization procedures
CA2305726A1 (en)	1997-10-07	1999-04-15	Regents Of The University Of California	Treating occlusive peripheral vascular disease and coronary disease with combinations of heparin and an adenoside a2 agonist, or with adenosine
US5972903A (en) *	1997-10-07	1999-10-26	Regents Of The University Of California Corporation	Method for promoting angiogenesis using heparin and adenosine
BR9911965A (pt) *	1998-07-09	2001-05-29	Sankyo Co	Composto, derivado de éster, éter ou n-alquilcarbamoìla farmaceuticamente aceitáveis, composição farmacêutica, uso de um composto, processo para o tratamento ou prevenção de uma infecção bacteriana, streptomices griseus, derivado de amida, processo para preparar um composto, e, cepa de streptomyces griseus
AR023463A1 (es)	1999-04-16	2002-09-04	Schering Corp	Uso de compuestos de azetidinona
TWI245047B (en) *	1999-08-20	2005-12-11	Sankyo Co	Novel A-500359 derivatives
US20050033044A1 (en)	2003-05-19	2005-02-10	Bristol-Myers Squibb Pharma Company	Methods for preparing 2-alkynyladenosine derivatives
JP2008530229A (ja)	2005-02-17	2008-08-07	ワイス	シクロアルキル縮合インドール、ベンゾチオフェン、ベンゾフランおよびインデン誘導体
US20090136460A1 (en) *	2007-07-10	2009-05-28	Vanderbilt University	Use of adenosine receptor ligands to promote cell adhesion in cell-based therapies
US10301348B2 (en) *	2013-10-23	2019-05-28	Academia Sinica	Compounds for use in prevention and treatment of neurodegenerative diseases and pain

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US4501735A (en) *	1983-12-05	1985-02-26	Warner-Lambert Company	N6-(1- and 2-benzocycloalkyl) adenosines
DE3406533A1 (de) *	1984-02-23	1985-08-29	Boehringer Mannheim Gmbh, 6800 Mannheim	Verwendung von adenosin-derivaten als antiallergica und arzneimittel, die diese enthalten
EP0300144A3 (en) *	1984-04-18	1989-09-27	Whitby Research Incorporated	N-6 alkyl substituted adenosine derivatives as cardiac vasodilators
US4594350A (en) *	1984-07-30	1986-06-10	Reagents Of University Of Minnesota	(3-ethoxypropionate) esters of cyclaradine
US4593019A (en) *	1984-10-26	1986-06-03	Warner-Lambert Company	N6 -tricyclic adenosines
US4791103A (en) *	1985-02-08	1988-12-13	Warner-Lambert Company	2,N6 -disubstituted adenosines, derivatives and methods of use
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US4600707A (en) *	1985-01-25	1986-07-15	Warner-Lambert Company	Benzothien-3-yl adenosine; benzothien-3-yl adenosine, S-oxide; and benzothien-3-yl, S,S-dioxide adenosine compounds
US4755594A (en) *	1986-01-31	1988-07-05	Warner-Lambert Company	N6 -substituted adenosines
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EP0277917A3 (en) *	1987-02-04	1990-03-28	Ciba-Geigy Ag	Certain adenosine 5'-carboxamide derivatives

1988
- 1988-05-13 US US07/193,968 patent/US5034381A/en not_active Expired - Fee Related
- 1988-12-29 EP EP88810900A patent/EP0323807A3/en not_active Withdrawn
- 1988-12-30 NO NO885821A patent/NO169843C/no unknown
1989
- 1989-01-03 IL IL88877A patent/IL88877A0/xx unknown
- 1989-01-04 FI FI890028A patent/FI90430C/fi not_active IP Right Cessation
- 1989-01-05 NZ NZ227542A patent/NZ227542A/en unknown
- 1989-01-05 ZA ZA8984A patent/ZA8984B/xx unknown
- 1989-01-05 CA CA000587534A patent/CA1325209C/en not_active Expired - Fee Related
- 1989-01-05 MX MX1444689A patent/MX14446A/es unknown
- 1989-01-05 PT PT89392A patent/PT89392B/pt not_active IP Right Cessation
- 1989-01-05 DD DD89324859A patent/DD283402A5/de unknown
- 1989-01-05 HU HU8933A patent/HU202550B/hu not_active IP Right Cessation
- 1989-01-06 JP JP64000590A patent/JPH01265100A/ja active Pending
- 1989-01-06 PH PH39015A patent/PH26672A/en unknown
- 1989-01-06 DK DK005089A patent/DK5089A/da not_active Application Discontinuation
- 1989-01-06 AU AU27767/89A patent/AU618055B2/en not_active Ceased
- 1989-01-06 KR KR1019890000062A patent/KR890011903A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
DK5089A (da)	1989-07-08
NO885821L (no)	1989-07-10
PT89392B (pt)	1993-09-30
PH26672A (en)	1992-09-15
NO885821D0 (no)	1988-12-30
MX14446A (es)	1994-01-31
HUT48904A (en)	1989-07-28
AU618055B2 (en)	1991-12-12
EP0323807A2 (en)	1989-07-12
JPH01265100A (ja)	1989-10-23
EP0323807A3 (en)	1990-06-20
FI890028A0 (fi)	1989-01-04
NZ227542A (en)	1992-03-26
PT89392A (pt)	1990-02-08
HU202550B (en)	1991-03-28
IL88877A0 (en)	1989-08-15
FI890028A7 (fi)	1989-07-08
FI90430C (fi)	1994-02-10
FI90430B (fi)	1993-10-29
ZA8984B (en)	1989-08-30
KR890011903A (ko)	1989-08-23
DK5089D0 (da)	1989-01-06
NO169843C (no)	1992-08-12
US5034381A (en)	1991-07-23
AU2776789A (en)	1989-07-13
NO169843B (no)	1992-05-04
CA1325209C (en)	1993-12-14

Publication	Publication Date	Title
DD283402A5 (de)	1990-10-10	Verfahren zur herstellung von 2-substituierten adenosinderivaten
DE3689836T2 (de)	1994-09-22	Zyklische aminabkömmlinge.
DE69623631T2 (de)	2003-08-07	4-aryl-1-phenylalkyl-1,2,3,6-tetrahydropyridine als neurothophe und neuroprotektive wirkstoffe
DE69107250T2 (de)	1995-09-21	Neue 4-Aminobuttersäurederivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneizubereitungen.
DE69023928T2 (de)	1996-04-18	DIAMINVERBINDUNGEN UND ARZNEIMITTEL GEGEN CEREBRALE STöRUNGEN DIE DIESE ENTHALTEN.
DD273833A5 (de)	1989-11-29	N 9 - cyclopentylsubstituierte adeninderivate
DE68908374T2 (de)	1994-01-05	Propenonoximether, Verfahren zu dessen Herstellung sowie diese enthaltende Arzneinmittel.
CH660484A5 (de)	1987-04-30	In 1-stellung durch einen heterocyclischen rest substituierte 4-((2,5-pyrrolidindion-1-yl)alkyl)piperazin-verbindungen.
DD284679A5 (de)	1990-11-21	Verfahren zur herstellung von adenosin 5'-carboamidderivate
CH648553A5 (de)	1985-03-29	Neue 3,4-dihydro-5h-2,3-benzodiazepin-derivate und verfahren zur herstellung derselben.
DE69329894T2 (de)	2001-05-03	Arylamidderivate
DE68904586T2 (de)	1993-08-19	Histamin-derivat, verfahren zu dessen herstellung und therapeutischen anwendung.
DE69408580T2 (de)	1998-06-18	2-amino-1,2,3,4-tetrahydronaphthalenderivate mit cardiovaskulärer wirkung
DD299424A5 (de)	1992-04-16	Phenolderivate zur foerderung des menschlichen nervenwachstumsfaktors
DE2940833A1 (de)	1980-04-30	2-methyl-dihydropyridin-verbindung, verfahren zu ihrer herstellung und sie enthaltendes pharmazeutisches mittel
DE69116237T2 (de)	1996-07-25	Derivate von Hexahydroazepine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
DE69719511T2 (de)	2003-10-02	Antivirale 2,4-pyrimidindion-derivate und verfahren zu ihrer herstellung
EP0033156A2 (de)	1981-08-05	1-Phenyl-2-cyclohexen-1-alkylamin-Derivate, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
DE69302544T2 (de)	1996-09-19	2-amino-1,2,3,4-tetrahydronaphthalen derivate mit wirkung auf das kardiovasculäre system, verfahren zu deren herstellung und deren pharmazeutische zusammensetzungen
DD284025A5 (de)	1990-10-31	Verfahren zur herstellung von imidazo(4,5-b)pyridin-derivaten
DE2461802A1 (de)	1975-07-17	Pyrazinderivate
DE68905171T2 (de)	1993-06-17	Benzol-derivate, ihre herstellung und pharmazeutische zusammensetzungen, die diese enthalten.
DE3813531A1 (de)	1988-11-10	Neue 2-aminoalkyl-4-benzyl-1-(2h)-phthalazinon-derivate
DE69110217T2 (de)	1996-02-29	Derivate der Kaffeinsäure und sie enthaltende pharmazeutische Zusammensetzungen.
DE3782378T2 (de)	1993-03-11	Dihydropyridinderivate und deren pharmazeutische zusammensetzungen.