DD273833A5 - N 9 - cyclopentylsubstituierte adeninderivate - Google Patents

N 9 - cyclopentylsubstituierte adeninderivate Download PDF

Info

Publication number: DD273833A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; hydrogen; alpha; lower alkyl; compound
Prior art date: 1986-11-14

Application number

DD87308972A

Other languages

German (de)

English (en)

Inventor

Jen Chen

Alan J Hutchison

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.)

1986-11-14

Filing date

1987-11-12

Publication date

1989-11-29

1987-11-12 Application filed by ��@��@��k�� filed Critical ��@��@��k��

1989-11-29 Publication of DD273833A5 publication Critical patent/DD273833A5/de

Links

GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 title claims description 7
150000001875 compounds Chemical class 0.000 claims abstract description 167
-1 N9-cyclopentyl-substituted adenine Chemical class 0.000 claims abstract description 95
238000000034 method Methods 0.000 claims abstract description 65
238000002360 preparation method Methods 0.000 claims abstract description 22
230000008569 process Effects 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 79
239000001257 hydrogen Substances 0.000 claims description 78
125000000217 alkyl group Chemical group 0.000 claims description 67
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
150000003839 salts Chemical class 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 39
239000007858 starting material Substances 0.000 claims description 34
150000002148 esters Chemical class 0.000 claims description 32
150000002431 hydrogen Chemical class 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 24
150000002367 halogens Chemical class 0.000 claims description 24
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 21
125000003118 aryl group Chemical group 0.000 claims description 21
239000000460 chlorine Substances 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
229910052801 chlorine Inorganic materials 0.000 claims description 15
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 15
239000002585 base Substances 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 12
125000001589 carboacyl group Chemical group 0.000 claims description 10
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000002947 alkylene group Chemical group 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
230000003287 optical effect Effects 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 5
125000004849 alkoxymethyl group Chemical group 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
229910052717 sulfur Chemical group 0.000 claims description 5
239000011593 sulfur Chemical group 0.000 claims description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
150000003254 radicals Chemical class 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000003435 aroyl group Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000005605 benzo group Chemical group 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
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 3
229940079593 drug Drugs 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
AYVGBNGTBQLJBG-UHFFFAOYSA-N [3-(hydroxymethyl)cyclopentyl]methanol Chemical compound OCC1CCC(CO)C1 AYVGBNGTBQLJBG-UHFFFAOYSA-N 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
125000004135 2-norbornyl group Chemical group [H]C1([H])C([H])([H])C2([H])C([H])([H])C1([H])C([H])([H])C2([H])* 0.000 claims 1
125000001054 5 membered carbocyclic group Chemical group 0.000 claims 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
229920006395 saturated elastomer Polymers 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
241000124008 Mammalia Species 0.000 abstract description 13
229940121359 adenosine receptor antagonist Drugs 0.000 abstract description 6
239000000296 purinergic P1 receptor antagonist Substances 0.000 abstract description 6
102000009346 Adenosine receptors Human genes 0.000 abstract description 5
108050000203 Adenosine receptors Proteins 0.000 abstract description 5
239000003446 ligand Substances 0.000 abstract description 4
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 abstract description 2
238000000926 separation method Methods 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 94
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
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 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 26
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000007787 solid Substances 0.000 description 21
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
239000002126 C01EB10 - Adenosine Substances 0.000 description 17
239000002253 acid Substances 0.000 description 17
229960005305 adenosine Drugs 0.000 description 17
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 15
239000012043 crude product Substances 0.000 description 15
238000002844 melting Methods 0.000 description 14
230000008018 melting Effects 0.000 description 14
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
235000019341 magnesium sulphate Nutrition 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
238000009833 condensation Methods 0.000 description 8
230000005494 condensation Effects 0.000 description 8
230000000694 effects Effects 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
239000000047 product Substances 0.000 description 8
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 8
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
230000002441 reversible effect Effects 0.000 description 7
239000000725 suspension Substances 0.000 description 7
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 6
206010020772 Hypertension Diseases 0.000 description 6
241000700159 Rattus Species 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 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
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000002798 polar solvent Substances 0.000 description 5
239000008107 starch Substances 0.000 description 5
230000000638 stimulation Effects 0.000 description 5
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
208000028017 Psychotic disease Diseases 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
208000007536 Thrombosis Diseases 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000006735 epoxidation reaction Methods 0.000 description 4
150000002118 epoxides Chemical class 0.000 description 4
230000001077 hypotensive effect Effects 0.000 description 4
239000002198 insoluble material Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
201000000980 schizophrenia Diseases 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
238000003756 stirring Methods 0.000 description 4
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
FHBLBGKCJWORQJ-UHFFFAOYSA-N 2,4,6-trichloropyrimidin-5-amine Chemical compound NC1=C(Cl)N=C(Cl)N=C1Cl FHBLBGKCJWORQJ-UHFFFAOYSA-N 0.000 description 3
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
229930024421 Adenine Natural products 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
229910000831 Steel Inorganic materials 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
229960000643 adenine Drugs 0.000 description 3
230000036772 blood pressure Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
150000001941 cyclopentenes Chemical class 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
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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125000000524 functional group Chemical group 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
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YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
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239000011734 sodium Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
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238000003797 solvolysis reaction Methods 0.000 description 3
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238000011699 spontaneously hypertensive rat Methods 0.000 description 3
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NFUVPOQBQIPJGJ-UHFFFAOYSA-N tert-butyl 2-[4-(2-aminoethyl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)C(C)C1=CC=C(CCN)C=C1 NFUVPOQBQIPJGJ-UHFFFAOYSA-N 0.000 description 3
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AYKYOOPFBCOXSL-UHFFFAOYSA-N (4-hydroxyphenyl)acetonitrile Chemical compound OC1=CC=C(CC#N)C=C1 AYKYOOPFBCOXSL-UHFFFAOYSA-N 0.000 description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
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HBJGQJWNMZDFKL-UHFFFAOYSA-N 2-chloro-7h-purin-6-amine Chemical compound NC1=NC(Cl)=NC2=C1NC=N2 HBJGQJWNMZDFKL-UHFFFAOYSA-N 0.000 description 2
ILQVLBMOQOCNKB-UHFFFAOYSA-N 2-n-(2-phenylethyl)-7h-purine-2,6-diamine Chemical compound N=1C=2N=CNC=2C(N)=NC=1NCCC1=CC=CC=C1 ILQVLBMOQOCNKB-UHFFFAOYSA-N 0.000 description 2
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 2
QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 2
229940122614 Adenosine receptor agonist Drugs 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
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
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HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
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NTBIYBAYFBNTCD-KBPBESRZSA-N dibenzoyl (2s,3s)-2,3-dihydroxybutanedioate Chemical compound O=C([C@@H](O)[C@H](O)C(=O)OC(=O)C=1C=CC=CC=1)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-KBPBESRZSA-N 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
MOXXPQWMYMUHHV-UHFFFAOYSA-N diethoxymethanol Chemical compound CCOC(O)OCC MOXXPQWMYMUHHV-UHFFFAOYSA-N 0.000 description 1
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
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150000002170 ethers Chemical class 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
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150000004677 hydrates Chemical class 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
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238000007327 hydrogenolysis reaction Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
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235000010981 methylcellulose Nutrition 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
XUGWUUDOWNZAGW-UHFFFAOYSA-N neplanocin A Natural products C1=NC=2C(N)=NC=NC=2N1C1C=C(CO)C(O)C1O XUGWUUDOWNZAGW-UHFFFAOYSA-N 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
KBQNBXKLWZDDMP-UHFFFAOYSA-N oxathietane 2,2-dioxide Chemical compound O=S1(=O)CCO1 KBQNBXKLWZDDMP-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
229940117803 phenethylamine Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 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
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical class CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
150000003109 potassium Chemical class 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000009987 spinning Methods 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
CMJIKWRJLCDJQU-UHFFFAOYSA-N tert-butyl 2-[4-(2-aminoethyl)phenyl]acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=C(CCN)C=C1 CMJIKWRJLCDJQU-UHFFFAOYSA-N 0.000 description 1
BWVMXUURLPNRIW-UHFFFAOYSA-N tert-butyl 2-[4-(2-aminoethyl)phenyl]propanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)C(C)C1=CC=C(CCN)C=C1 BWVMXUURLPNRIW-UHFFFAOYSA-N 0.000 description 1
ZNUXHWCRPZCQPJ-UHFFFAOYSA-N tert-butyl 2-[4-(cyanomethyl)phenyl]prop-2-enoate Chemical compound CC(C)(C)OC(=O)C(=C)C1=CC=C(CC#N)C=C1 ZNUXHWCRPZCQPJ-UHFFFAOYSA-N 0.000 description 1
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
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-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
GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D303/46—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by amide or nitrile radicals

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (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)
Neurosurgery (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Vascular Medicine (AREA)
Diabetes (AREA)
Hematology (AREA)
Psychiatry (AREA)
Urology & Nephrology (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

DD87308972A 1986-11-14 1987-11-12 N 9 - cyclopentylsubstituierte adeninderivate DD273833A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US93132786A	1986-11-14	1986-11-14

Publications (1)

Publication Number	Publication Date
DD273833A5 true DD273833A5 (de)	1989-11-29

Family

ID=25460605

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD87308972A DD273833A5 (de)	1986-11-14	1987-11-12	N 9 - cyclopentylsubstituierte adeninderivate

Country Status (15)

Country	Link
EP (1)	EP0267878A1 (da)
JP (1)	JPS63135384A (da)
KR (1)	KR880006241A (da)
AU (1)	AU608258B2 (da)
CA (1)	CA1288431C (da)
DD (1)	DD273833A5 (da)
DK (1)	DK596087A (da)
FI (1)	FI874982A7 (da)
HU (1)	HU198489B (da)
IL (1)	IL84414A0 (da)
NO (1)	NO166184C (da)
NZ (1)	NZ222527A (da)
PH (1)	PH25044A (da)
PT (1)	PT86120B (da)
ZA (1)	ZA878527B (da)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IN164556B (da) *	1986-03-06	1989-04-08	Takeda Chemical Industries Ltd
US5063233A (en) *	1986-11-14	1991-11-05	Ciba-Geigy Corporation	N9 -cyclopentyl-substituted adenine derivatives useful as adenosine receptor agonists
US5015739A (en) *	1988-04-22	1991-05-14	Schering Corporation	Processes for preparation of cyclopentyl purine derivatives
GB8813148D0 (en) *	1988-06-03	1988-07-06	Glaxo Group Ltd	Chemical compounds
US5216141A (en) *	1988-06-06	1993-06-01	Benner Steven A	Oligonucleotide analogs containing sulfur linkages
HU204843B (en) *	1988-09-27	1992-02-28	Merrell Dow Pharma	Process for producing 2'-halogen-methylidene adenosine derivatives and pharmaceutical compositions comprising same
GB8826205D0 (en) *	1988-11-09	1988-12-14	Wellcome Found	Heterocyclic compounds
US5312961A (en) *	1989-02-14	1994-05-17	Elf Sanofi	2-amino-7-hydroxytetralin carboxylalkyl ethers
GB8916478D0 (en) *	1989-07-19	1989-09-06	Glaxo Group Ltd	Chemical process
GB8916479D0 (en) *	1989-07-19	1989-09-06	Glaxo Group Ltd	Chemical process
GB8926417D0 (en) *	1989-11-22	1990-01-10	Wellcome Found	Heterocyclic compounds
US5470857A (en) *	1990-09-14	1995-11-28	Marion Merrell Dow Inc.	Carbocyclic nucleoside analogs useful as immunosuppressants
US5514688A (en) *	1990-09-14	1996-05-07	Merrell Dow Pharmaceuticals Inc.	Carbocyclic adenosine analogs useful as immunosuppressants
US5561134A (en) *	1990-09-25	1996-10-01	Rhone-Poulenc Rorer Pharmaceuticals Inc.	Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties
GB9108376D0 (en) *	1991-04-19	1991-06-05	Enzymatix Ltd	Cyclopentenes
US5206222A (en) *	1991-05-22	1993-04-27	Vanderbilt University	Methods for the reduction of myocardial reperfusion injury
US5723466A (en) *	1991-12-06	1998-03-03	Hoechst Marion Roussel, Inc.	Trans cyclopentanyl purine analogs useful as immunosuppressants
US5817672A (en) *	1991-12-06	1998-10-06	Hoechst Marion Roussel, Inc.	Trans cyclopentanyl purine analogs useful as immunosuppressants
US5817660A (en) *	1991-12-06	1998-10-06	Hoechst Marion Roussel, Inc.	Trans cyclopentanyl purine analogs useful as immunosuppressants
US5817661A (en)	1991-12-06	1998-10-06	Hoechst Marion Roussel, Inc.	Trans cyclopentanyl purine analogs useful as immunosuppressants
FR2685918B1 (fr) *	1992-01-08	1995-06-23	Union Pharma Scient Appl	Nouveaux derives de l'adenosine, leurs procedes de preparation, compositions pharmaceutiques les contenant.
US5840923A (en) *	1992-04-21	1998-11-24	Chiroscience Limited	Chiral cyclopentene derivatives and their preparation
JPH08505835A (ja) *	1992-04-21	1996-06-25	カイロサイエンス・リミテッド	キラルシクロペンテン誘導体及びそれらの製造
IT1254915B (it) *	1992-04-24	1995-10-11	Gloria Cristalli	Derivati di adenosina ad attivita' a2 agonista
EP0577558A2 (de) *	1992-07-01	1994-01-05	Ciba-Geigy Ag	Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
GB9414208D0 (en) *	1994-07-14	1994-08-31	Glaxo Group Ltd	Compounds
WO1996019478A1 (en) *	1994-12-19	1996-06-27	Novartis Ag	6'-substituted carbocyclic nucleosides
AR023463A1 (es)	1999-04-16	2002-09-04	Schering Corp	Uso de compuestos de azetidinona
AU3851601A (en) *	2000-02-18	2001-08-27	Southern Res Inst	Methods for synthesizing 2-chloro-9-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-9h- purin-6-amine
US20050033044A1 (en)	2003-05-19	2005-02-10	Bristol-Myers Squibb Pharma Company	Methods for preparing 2-alkynyladenosine derivatives
GT200500281A (es)	2004-10-22	2006-04-24	Novartis Ag	Compuestos organicos.
GB0500785D0 (en)	2005-01-14	2005-02-23	Novartis Ag	Organic compounds
PT2322525E (pt)	2006-04-21	2013-12-26	Novartis Ag	Derivados de purina para utilização como agonistas do recetor de adenosina a2a
GB0607950D0 (en)	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
EP1889846A1 (en)	2006-07-13	2008-02-20	Novartis AG	Purine derivatives as A2a agonists
EP1903044A1 (en)	2006-09-14	2008-03-26	Novartis AG	Adenosine Derivatives as A2A Receptor Agonists
CA2817975C (en) *	2010-11-16	2020-03-31	Michael Kahn	Cbp/catenin antagonists for enhancing asymmetric division of somatic stem cells
CN105061431B (zh) *	2015-07-28	2017-03-29	山东百诺医药股份有限公司	6‑n‑（2‑（甲硫基）乙基）‑2‑（（3,3,3‑三氟丙基）硫代）‑9h‑嘌呤及其制备方法和应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2610985A1 (de) *	1976-03-16	1977-09-29	Byk Gulden Lomberg Chem Fab	Arzneimittel enthaltend beta-d-1 (6-amino-9h-purin-9-yl)-1-deoxyribofuranuronsaeurederivate
US4345984A (en) *	1981-03-02	1982-08-24	The Procter & Gamble Company	Novel prostaglandin analogues and process for making same
US4543255A (en) *	1984-05-10	1985-09-24	Southern Research Institute	Carbocyclic analogs of purine 2'-deoxyribofuranosides
US4742064A (en) *	1985-09-10	1988-05-03	Regents Of The University Of Minnesota	Antiviral carbocyclic analogs of xylofuranosylpurines

1987
- 1987-11-09 EP EP87810647A patent/EP0267878A1/en not_active Withdrawn
- 1987-11-09 IL IL84414A patent/IL84414A0/xx unknown
- 1987-11-11 FI FI874982A patent/FI874982A7/fi not_active IP Right Cessation
- 1987-11-12 PT PT86120A patent/PT86120B/pt not_active IP Right Cessation
- 1987-11-12 CA CA000551656A patent/CA1288431C/en not_active Expired - Lifetime
- 1987-11-12 DD DD87308972A patent/DD273833A5/de not_active IP Right Cessation
- 1987-11-12 NZ NZ222527A patent/NZ222527A/xx unknown
- 1987-11-13 ZA ZA878527A patent/ZA878527B/xx unknown
- 1987-11-13 AU AU81193/87A patent/AU608258B2/en not_active Ceased
- 1987-11-13 NO NO874749A patent/NO166184C/no unknown
- 1987-11-13 JP JP62285628A patent/JPS63135384A/ja active Pending
- 1987-11-13 HU HU875070A patent/HU198489B/hu unknown
- 1987-11-13 DK DK596087A patent/DK596087A/da not_active Application Discontinuation
- 1987-11-13 PH PH36065A patent/PH25044A/en unknown
- 1987-11-23 KR KR870012780A patent/KR880006241A/ko not_active Withdrawn

Also Published As

Publication number	Publication date
NO874749D0 (no)	1987-11-13
HUT45057A (en)	1988-05-30
NZ222527A (en)	1990-08-28
ZA878527B (en)	1988-05-16
KR880006241A (ko)	1988-07-22
CA1288431C (en)	1991-09-03
AU8119387A (en)	1988-05-19
NO166184C (no)	1991-06-12
NO166184B (no)	1991-03-04
AU608258B2 (en)	1991-03-28
PH25044A (en)	1991-01-28
FI874982A0 (fi)	1987-11-11
DK596087A (da)	1988-05-15
PT86120A (en)	1987-12-01
FI874982A7 (fi)	1988-05-15
JPS63135384A (ja)	1988-06-07
HU198489B (en)	1989-10-30
IL84414A0 (en)	1988-04-29
PT86120B (pt)	1990-08-31
NO874749L (no)	1988-05-16
DK596087D0 (da)	1987-11-13
EP0267878A1 (en)	1988-05-18

Legal Events

Date	Code	Title	Description
1995-08-31	ENJ	Ceased due to non-payment of renewal fee

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