FI109129B - Menetelmä 2-substituoitujen adenosiinien valmistamiseksi, joilla on A-2-reseptoriaffiniteetti - Google Patents

Menetelmä 2-substituoitujen adenosiinien valmistamiseksi, joilla on A-2-reseptoriaffiniteetti Download PDF

Info

Publication number: FI109129B
Authority: FI; Finland
Prior art keywords: adenosine; receptors; receptor; binding; compound
Prior art date: 1992-09-30

Application number

FI951500A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI951500L (fi

FI951500A0 (fi

Inventor

Norton Paul Peet

Philip Marvin Weintraub

David Roger Borcherding

Nelsen Lowel Lentz

Original Assignee

Merrell Dow Pharma

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.)

1992-09-30

Filing date

1995-03-29

Publication date

2002-05-31

1995-03-29 Application filed by Merrell Dow Pharma filed Critical Merrell Dow Pharma

1995-03-29 Publication of FI951500L publication Critical patent/FI951500L/fi

1995-03-29 Publication of FI951500A0 publication Critical patent/FI951500A0/fi

2002-05-31 Application granted granted Critical

2002-05-31 Publication of FI109129B publication Critical patent/FI109129B/fi

Links

238000000034 method Methods 0.000 title claims description 16
-1 2-substituted adenosines Chemical class 0.000 title claims description 11
230000008569 process Effects 0.000 title claims description 5
238000002360 preparation method Methods 0.000 title claims description 4
102100025358 Probable G-protein coupled receptor 162 Human genes 0.000 title description 24
150000001875 compounds Chemical class 0.000 claims abstract description 35
SASWNLAIMHWYRS-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2-phenylpropan-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=CC=CC=1C(C)(C)NC(N=C12)=NC(N)=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SASWNLAIMHWYRS-LSCFUAHRSA-N 0.000 claims description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
YFJCRJZTDYDCRZ-MCDZGGTQSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;hydrochloride Chemical compound Cl.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YFJCRJZTDYDCRZ-MCDZGGTQSA-N 0.000 claims 1
108050000203 Adenosine receptors Proteins 0.000 abstract description 35
102000009346 Adenosine receptors Human genes 0.000 abstract description 35
150000003838 adenosines Chemical class 0.000 abstract description 17
230000027455 binding Effects 0.000 abstract description 17
230000000694 effects Effects 0.000 abstract description 15
230000001766 physiological effect Effects 0.000 abstract description 8
238000001727 in vivo Methods 0.000 abstract description 6
230000036772 blood pressure Effects 0.000 abstract description 5
238000000338 in vitro Methods 0.000 abstract description 4
239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
239000003379 purinergic P1 receptor agonist Substances 0.000 abstract description 2
230000003247 decreasing effect Effects 0.000 abstract 2
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 61
239000002126 C01EB10 - Adenosine Substances 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
229960005305 adenosine Drugs 0.000 description 30
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
102000005962 receptors Human genes 0.000 description 19
108020003175 receptors Proteins 0.000 description 19
150000003335 secondary amines Chemical class 0.000 description 17
239000012528 membrane Substances 0.000 description 16
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 14
230000008484 agonism Effects 0.000 description 12
239000000872 buffer Substances 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
238000012360 testing method Methods 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
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
239000005557 antagonist Substances 0.000 description 8
210000004556 brain Anatomy 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000012141 concentrate Substances 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000000203 mixture Substances 0.000 description 8
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
210000003169 central nervous system Anatomy 0.000 description 7
230000002526 effect on cardiovascular system Effects 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000000556 agonist Substances 0.000 description 6
230000008485 antagonism Effects 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
101710095468 Cyclase Proteins 0.000 description 5
241000700159 Rattus Species 0.000 description 5
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 5
238000003556 assay Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000003446 ligand Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
238000011534 incubation Methods 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
239000008188 pellet Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
RIRGCFBBHQEQQH-SSFGXONLSA-N (-)-n6-(2-phenylisopropyl)adenosine Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=CN=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)C1=CC=CC=C1 RIRGCFBBHQEQQH-SSFGXONLSA-N 0.000 description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 3
CLIGSMOZKDCDRZ-UHFFFAOYSA-N 8-phenyl-1,3-dipropyl-7H-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=CC=C1 CLIGSMOZKDCDRZ-UHFFFAOYSA-N 0.000 description 3
230000001773 anti-convulsant effect Effects 0.000 description 3
239000002585 base Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
230000006870 function Effects 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229940094443 oxytocics prostaglandins Drugs 0.000 description 3
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
230000035790 physiological processes and functions Effects 0.000 description 3
150000003180 prostaglandins Chemical class 0.000 description 3
239000000296 purinergic P1 receptor antagonist Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
AQFLVLHRZFLDDV-SECBINFHSA-N (1r)-1-phenylpropan-1-amine Chemical compound CC[C@@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-SECBINFHSA-N 0.000 description 2
UGRNVLGKAGREKS-GCXDCGAKSA-N (1r,2s,3r,5r)-3-(6-aminopurin-9-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1C[C@H](CO)[C@@H](O)[C@H]1O UGRNVLGKAGREKS-GCXDCGAKSA-N 0.000 description 2
CHMUHOFITZIING-XNIJJKJLSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-2-cyclohexyl-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@]1(C2CCCCC2)O[C@H](CO)[C@@H](O)[C@H]1O CHMUHOFITZIING-XNIJJKJLSA-N 0.000 description 2
SASWNLAIMHWYRS-GDLHICMESA-N (2s,3r,4s,5r)-2-[6-amino-2-(2-phenylpropan-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=CC=CC=1C(C)(C)NC(N=C12)=NC(N)=C1N=CN2[C@H]1O[C@H](CO)[C@@H](O)[C@H]1O SASWNLAIMHWYRS-GDLHICMESA-N 0.000 description 2
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
101150007969 ADORA1 gene Proteins 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
108010041368 Adenosine A2 Receptors Proteins 0.000 description 2
102000000506 Adenosine A2 Receptors Human genes 0.000 description 2
102000055025 Adenosine deaminases Human genes 0.000 description 2
XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
102000030621 adenylate cyclase Human genes 0.000 description 2
108060000200 adenylate cyclase Proteins 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
239000002269 analeptic agent Substances 0.000 description 2
239000001961 anticonvulsive agent Substances 0.000 description 2
229960003965 antiepileptics Drugs 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
229960001948 caffeine Drugs 0.000 description 2
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000003365 glass fiber Substances 0.000 description 2
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
229910052736 halogen Chemical group 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
230000036543 hypotension Effects 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
229940127240 opiate Drugs 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
230000006461 physiological response Effects 0.000 description 2
239000002243 precursor Substances 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000000932 sedative agent Substances 0.000 description 2
230000001624 sedative effect Effects 0.000 description 2
230000009870 specific binding Effects 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
AQFLVLHRZFLDDV-VIFPVBQESA-N (1s)-1-phenylpropan-1-amine Chemical compound CC[C@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-VIFPVBQESA-N 0.000 description 1
UYQFGWISZQZGQU-DKZDHXMOSA-N (2R,3R,4S,5R)-2-(5-chloro-6-iminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(=N)C2(Cl)N=C1 UYQFGWISZQZGQU-DKZDHXMOSA-N 0.000 description 1
IOODSIQZGAKRBS-JJPFLPBXSA-N (2r,3r,4s,5r)-2-[6-amino-2-(1-phenylpropylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=CC=CC=1C(CC)NC(N=C12)=NC(N)=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O IOODSIQZGAKRBS-JJPFLPBXSA-N 0.000 description 1
KNGDTUPYRQLCDN-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[6-amino-2-(3-phenylpropylamino)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=1NCCCC1=CC=CC=C1 KNGDTUPYRQLCDN-SCFUHWHPSA-N 0.000 description 1
RIRGCFBBHQEQQH-UVCRECLJSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-(1-phenylpropan-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N=1C=NC=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C=1NC(C)CC1=CC=CC=C1 RIRGCFBBHQEQQH-UVCRECLJSA-N 0.000 description 1
IOODSIQZGAKRBS-IBOWEFIJSA-N (2s,3r,4s,5r)-2-[6-amino-2-(1-phenylpropylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=CC=CC=1C(CC)NC(N=C12)=NC(N)=C1N=CN2[C@H]1O[C@H](CO)[C@@H](O)[C@H]1O IOODSIQZGAKRBS-IBOWEFIJSA-N 0.000 description 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
DKVDZCADCDCTFQ-UHFFFAOYSA-N 8-(2,3-diethylphenyl)-3,7-dihydropurine-2,6-dione Chemical compound C(C)C=1C(=C(C=CC=1)C1=NC=2NC(NC(C=2N1)=O)=O)CC DKVDZCADCDCTFQ-UHFFFAOYSA-N 0.000 description 1
RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 description 1
108010060263 Adenosine A1 Receptor Proteins 0.000 description 1
102000030814 Adenosine A1 receptor Human genes 0.000 description 1
229910002703 Al K Inorganic materials 0.000 description 1
235000002198 Annona diversifolia Nutrition 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
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 1
241000282838 Lama Species 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
102000015433 Prostaglandin Receptors Human genes 0.000 description 1
108010050183 Prostaglandin Receptors Proteins 0.000 description 1
102000000033 Purinergic Receptors Human genes 0.000 description 1
108010080192 Purinergic Receptors Proteins 0.000 description 1
102100028255 Renin Human genes 0.000 description 1
108090000783 Renin Proteins 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
238000012338 Therapeutic targeting Methods 0.000 description 1
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000002597 adenosine A2 receptor agonist Substances 0.000 description 1
229940121359 adenosine receptor antagonist Drugs 0.000 description 1
210000001789 adipocyte Anatomy 0.000 description 1
230000001919 adrenal effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229940025084 amphetamine Drugs 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
230000002429 anti-coagulating effect Effects 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
230000002180 anti-stress Effects 0.000 description 1
239000000924 antiasthmatic agent Substances 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229940127219 anticoagulant drug Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
150000001561 benzopteridines Chemical class 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000004044 bronchoconstricting agent Substances 0.000 description 1
230000003435 bronchoconstrictive effect Effects 0.000 description 1
229910001424 calcium ion Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000002371 cardiac agent Substances 0.000 description 1
230000003684 cardiac depression Effects 0.000 description 1
239000002327 cardiovascular agent Substances 0.000 description 1
229940125692 cardiovascular agent Drugs 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000003576 central nervous system agent Substances 0.000 description 1
229940125693 central nervous system agent Drugs 0.000 description 1
239000003874 central nervous system depressant Substances 0.000 description 1
230000008859 change Effects 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000003086 colorant Substances 0.000 description 1
210000001608 connective tissue cell Anatomy 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
229940095074 cyclic amp Drugs 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
235000015872 dietary supplement Nutrition 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000002224 dissection Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000012636 effector Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000003925 fat Substances 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
239000010200 folin Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000001577 neostriatum Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000000803 paradoxical effect Effects 0.000 description 1
230000036581 peripheral resistance Effects 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000001042 pteridinyl group Chemical class N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
210000005227 renal system Anatomy 0.000 description 1
238000011160 research Methods 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
241000894007 species Species 0.000 description 1
230000008925 spontaneous activity Effects 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
239000003826 tablet Substances 0.000 description 1
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 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
- 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

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

FI951500A 1992-09-30 1995-03-29 Menetelmä 2-substituoitujen adenosiinien valmistamiseksi, joilla on A-2-reseptoriaffiniteetti FI109129B (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US95418092A	1992-09-30	1992-09-30
US95418092		1992-09-30
US9308269		1993-09-02
PCT/US1993/008269 WO1994007905A1 (en)	1992-09-30	1993-09-02	2-substituted adenosines with a-2 receptor affinity

Publications (3)

Publication Number	Publication Date
FI951500L FI951500L (fi)	1995-03-29
FI951500A0 FI951500A0 (fi)	1995-03-29
FI109129B true FI109129B (fi)	2002-05-31

Family

ID=25495051

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI951500A FI109129B (fi)	1992-09-30	1995-03-29	Menetelmä 2-substituoitujen adenosiinien valmistamiseksi, joilla on A-2-reseptoriaffiniteetti

Country Status (19)

Country	Link
EP (1)	EP0662975B1 (es)
JP (1)	JPH08502069A (es)
KR (1)	KR100316354B1 (es)
AT (1)	ATE150761T1 (es)
AU (1)	AU672226B2 (es)
CA (1)	CA2145682C (es)
DE (1)	DE69309293T2 (es)
DK (1)	DK0662975T3 (es)
ES (1)	ES2102679T3 (es)
FI (1)	FI109129B (es)
GR (1)	GR3023761T3 (es)
HU (1)	HU220760B1 (es)
IL (2)	IL107101A0 (es)
MX (1)	MX9306032A (es)
NO (1)	NO303875B1 (es)
NZ (1)	NZ256195A (es)
TW (1)	TW302367B (es)
WO (1)	WO1994007905A1 (es)
ZA (1)	ZA937108B (es)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0015727D0 (en) *	2000-06-27	2000-08-16	Pfizer Ltd	Purine derivatives
US6921753B2 (en)	2000-06-27	2005-07-26	Pfizer Inc	Purine derivatives
GB0022695D0 (en)	2000-09-15	2000-11-01	Pfizer Ltd	Purine Derivatives

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5034381A (en) *	1988-01-07	1991-07-23	Ciba-Geigy Corporation	2-(substituted amino) adenosines as antihypertensives

1992
- 1992-09-24 IL IL107101A patent/IL107101A0/xx unknown
1993
- 1993-09-02 EP EP93921304A patent/EP0662975B1/en not_active Expired - Lifetime
- 1993-09-02 DK DK93921304.7T patent/DK0662975T3/da active
- 1993-09-02 NZ NZ256195A patent/NZ256195A/en unknown
- 1993-09-02 AU AU48446/93A patent/AU672226B2/en not_active Ceased
- 1993-09-02 DE DE69309293T patent/DE69309293T2/de not_active Expired - Fee Related
- 1993-09-02 AT AT93921304T patent/ATE150761T1/de not_active IP Right Cessation
- 1993-09-02 WO PCT/US1993/008269 patent/WO1994007905A1/en not_active Ceased
- 1993-09-02 ES ES93921304T patent/ES2102679T3/es not_active Expired - Lifetime
- 1993-09-02 KR KR1019950701220A patent/KR100316354B1/ko not_active Expired - Fee Related
- 1993-09-02 JP JP6509058A patent/JPH08502069A/ja active Pending
- 1993-09-02 HU HU9500918A patent/HU220760B1/hu not_active IP Right Cessation
- 1993-09-02 CA CA002145682A patent/CA2145682C/en not_active Expired - Fee Related
- 1993-09-24 IL IL10710193A patent/IL107101A/xx not_active IP Right Cessation
- 1993-09-24 ZA ZA937108A patent/ZA937108B/xx unknown
- 1993-09-25 TW TW082107911A patent/TW302367B/zh active
- 1993-09-29 MX MX9306032A patent/MX9306032A/es not_active IP Right Cessation
1995
- 1995-03-29 FI FI951500A patent/FI109129B/fi active
- 1995-03-29 NO NO951213A patent/NO303875B1/no unknown
1997
- 1997-06-11 GR GR970401405T patent/GR3023761T3/el unknown

Also Published As

Publication number	Publication date
IL107101A (en)	2000-07-16
JPH08502069A (ja)	1996-03-05
DE69309293T2 (de)	1997-07-10
NO951213L (no)	1995-03-29
AU4844693A (en)	1994-04-26
GR3023761T3 (en)	1997-09-30
DK0662975T3 (es)	1997-04-28
FI951500L (fi)	1995-03-29
NO951213D0 (no)	1995-03-29
WO1994007905A1 (en)	1994-04-14
MX9306032A (es)	1994-03-31
DE69309293D1 (de)	1997-04-30
ES2102679T3 (es)	1997-08-01
NO303875B1 (no)	1998-09-14
HU9500918D0 (en)	1995-05-29
KR100316354B1 (ko)	2002-09-26
EP0662975A1 (en)	1995-07-19
FI951500A0 (fi)	1995-03-29
CA2145682A1 (en)	1994-04-14
HUT72611A (en)	1996-05-28
HU220760B1 (hu)	2002-05-28
ZA937108B (en)	1994-05-17
ATE150761T1 (de)	1997-04-15
NZ256195A (en)	1996-05-28
AU672226B2 (en)	1996-09-26
TW302367B (es)	1997-04-11
KR950703572A (ko)	1995-09-20
IL107101A0 (en)	1993-12-28
EP0662975B1 (en)	1997-03-26
CA2145682C (en)	1998-11-10

Publication	Publication Date	Title
RU2633694C2 (ru)	2017-10-17	Дейтерированный фениламинопиримидин и фармацевтическая композиция, содержащая такое соединение
EP0390112B1 (en)	1998-01-28	Selective adenosine receptor agents
EP0449175B1 (en)	1997-07-30	Selective adenosine receptor agents
US5329007A (en)	1994-07-12	Selective adenosine receptor agents
FI109129B (fi)	2002-05-31	Menetelmä 2-substituoitujen adenosiinien valmistamiseksi, joilla on A-2-reseptoriaffiniteetti
US5064947A (en)	1991-11-12	Selective adenosine reseptor compounds
EP0390111B1 (en)	1994-09-14	Selective adenosine receptor compounds
US5391739A (en)	1995-02-21	Selective adenosine receptor agents
CN117677620A (zh)	2024-03-08	恩替卡韦（etv）的抗病毒前药及其制剂
US5426101A (en)	1995-06-20	2-substituted adenosines with A-2 receptor affinity
US5086176A (en)	1992-02-04	Tricyclic fused adenine derivatives
AU676323B2 (en)	1997-03-06	8-substituted xanthines as selective adenosine receptor agents
CN117126162A (zh)	2023-11-28	多取代杂环类化合物及其制备方法和应用

Legal Events

Date	Code	Title	Description
1997-01-14	GB	Transfer or assigment of application	Owner name: AHLSTROM MACHINERY OY