CA2242097C - Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques - Google Patents

Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques Download PDF

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Publication number: CA2242097C
Authority: CA; Canada
Prior art keywords: alkyl; phenyl; benzyl; compound; optionally substituted
Prior art date: 1996-07-20
Legal status (The legal status 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 status listed.): Expired - Fee Related

Application number

CA002242097A

Other languages

English (en)

Other versions

CA2242097A1 (fr

Inventor

Ulrike Kuefner-Muehl

Werner Kummer

Gerald Pohl

Wolfram Gaida

Erich Lehr

Joachim Mierau

Thomas Weiser

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Boehringer Ingelheim International GmbH

Original Assignee

Boehringer Ingelheim International GmbH

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.)

1996-07-20

Filing date

1998-06-26

Publication date

2003-05-13

1996-07-20 Priority to DE19629378A priority Critical patent/DE19629378A1/de

1996-07-20 Priority claimed from DE19629378A external-priority patent/DE19629378A1/de

1997-07-17 Priority to TR1998/01659T priority patent/TR199801659T2/xx

1997-07-17 Priority to DE59701467T priority patent/DE59701467D1/de

1997-07-17 Priority to SK1144-98A priority patent/SK114498A3/sk

1997-07-17 Priority to HU9902311A priority patent/HUP9902311A3/hu

1997-07-17 Priority to ZA976331A priority patent/ZA976331B/xx

1997-07-17 Priority to JP10505626A priority patent/JP3020281B2/ja

1997-07-17 Priority to EP97933683A priority patent/EP0880524B1/fr

1997-07-17 Priority to IL12645397A priority patent/IL126453A0/xx

1997-07-17 Priority to EP99119410A priority patent/EP0978517A3/fr

1997-07-17 Priority to EE9800451A priority patent/EE9800451A/xx

1997-07-17 Priority to CZ982654A priority patent/CZ265498A3/cs

1997-07-17 Priority to PL97328824A priority patent/PL328824A1/xx

1997-07-17 Priority to ES97933683T priority patent/ES2147453T3/es

1997-07-17 Priority to PCT/EP1997/003841 priority patent/WO1998003511A1/fr

1997-07-17 Priority to CA002256736A priority patent/CA2256736A1/fr

1997-07-17 Priority to CN97194506A priority patent/CN1219936A/zh

1997-07-17 Priority to DK97933683T priority patent/DK0880524T3/da

1997-07-17 Priority to BR9710747A priority patent/BR9710747A/pt

1997-07-17 Priority to PT97933683T priority patent/PT880524E/pt

1997-07-17 Priority to AT97933683T priority patent/ATE191913T1/de

1997-07-17 Priority to AU36955/97A priority patent/AU3695597A/en

1997-07-18 Priority to HR19629378.2A priority patent/HRP970395A2/hr

1997-07-18 Priority to IDP972495A priority patent/ID19106A/id

1998-06-26 Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH

1998-06-26 Priority to CA002242097A priority patent/CA2242097C/fr

1998-08-20 Priority to BG102707A priority patent/BG102707A/xx

1998-08-21 Priority to NO983860A priority patent/NO983860L/no

1998-09-08 Priority to ZA9808189A priority patent/ZA988189B/xx

1998-11-06 Priority to PL98329578A priority patent/PL329578A1/xx

1999-01-27 Priority to BR9900187-0A priority patent/BR9900187A/pt

1999-02-19 Priority to AU17418/99A priority patent/AU1741899A/en

1999-06-25 Priority to IDP990618D priority patent/ID23607A/id

1999-12-26 Publication of CA2242097A1 publication Critical patent/CA2242097A1/fr

2000-04-26 Priority to US09/559,806 priority patent/US6492377B1/en

2000-06-30 Priority to GR20000401543T priority patent/GR3033842T3/el

2003-05-13 Publication of CA2242097C publication Critical patent/CA2242097C/fr

2003-05-13 Application granted granted Critical

2018-06-26 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
238000004519 manufacturing process Methods 0.000 title claims description 6
-1 phenyloxy Chemical group 0.000 claims description 253
229910052739 hydrogen Inorganic materials 0.000 claims description 201
150000001875 compounds Chemical class 0.000 claims description 200
239000001257 hydrogen Substances 0.000 claims description 136
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 135
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 133
150000002431 hydrogen Chemical class 0.000 claims description 116
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 98
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 81
229910052736 halogen Inorganic materials 0.000 claims description 78
150000002367 halogens Chemical class 0.000 claims description 78
239000000203 mixture Substances 0.000 claims description 78
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 73
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 69
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 67
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 50
229910052757 nitrogen Inorganic materials 0.000 claims description 49
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
239000002253 acid Substances 0.000 claims description 42
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 42
229910052760 oxygen Inorganic materials 0.000 claims description 40
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 37
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 36
239000001301 oxygen Substances 0.000 claims description 36
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 35
125000004093 cyano group Chemical group *C#N 0.000 claims description 35
125000005842 heteroatom Chemical group 0.000 claims description 35
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 31
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 29
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 27
239000000460 chlorine Chemical group 0.000 claims description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 26
239000005864 Sulphur Substances 0.000 claims description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
229910052801 chlorine Chemical group 0.000 claims description 26
150000002832 nitroso derivatives Chemical class 0.000 claims description 26
125000004076 pyridyl group Chemical group 0.000 claims description 26
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 24
238000006243 chemical reaction Methods 0.000 claims description 23
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 22
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 22
150000004985 diamines Chemical class 0.000 claims description 22
150000001412 amines Chemical class 0.000 claims description 21
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 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 19
239000011737 fluorine Substances 0.000 claims description 19
229910052731 fluorine Inorganic materials 0.000 claims description 19
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 18
125000000217 alkyl group Chemical group 0.000 claims description 18
239000002904 solvent Substances 0.000 claims description 18
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 17
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 15
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
229910052794 bromium Inorganic materials 0.000 claims description 14
201000010099 disease Diseases 0.000 claims description 14
125000002541 furyl group Chemical group 0.000 claims description 14
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 12
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 12
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
125000005485 noradamantyl group Chemical group 0.000 claims description 12
125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 11
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 11
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 10
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 10
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 10
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 10
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 10
XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims description 10
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 10
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 10
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 10
125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 claims description 10
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 10
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 10
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 10
229920006395 saturated elastomer Polymers 0.000 claims description 10
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
150000003852 triazoles Chemical class 0.000 claims description 10
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 9
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 9
125000001153 fluoro group Chemical group F* 0.000 claims description 9
RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 9
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 9
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 8
239000002168 alkylating agent Substances 0.000 claims description 8
229940100198 alkylating agent Drugs 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
208000035475 disorder Diseases 0.000 claims description 7
239000003960 organic solvent Substances 0.000 claims description 7
125000004193 piperazinyl group Chemical group 0.000 claims description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 6
108050000203 Adenosine receptors Proteins 0.000 claims description 6
102000009346 Adenosine receptors Human genes 0.000 claims description 6
230000004913 activation Effects 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
230000001575 pathological effect Effects 0.000 claims description 6
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 5
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 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 5
208000024827 Alzheimer disease Diseases 0.000 claims description 5
201000003883 Cystic fibrosis Diseases 0.000 claims description 5
208000019695 Migraine disease Diseases 0.000 claims description 5
208000018737 Parkinson disease Diseases 0.000 claims description 5
210000003169 central nervous system Anatomy 0.000 claims description 5
206010027599 migraine Diseases 0.000 claims description 5
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 5
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 4
IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 4
BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 4
208000024172 Cardiovascular disease Diseases 0.000 claims description 4
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 4
210000003630 histaminocyte Anatomy 0.000 claims description 4
208000015122 neurodegenerative disease Diseases 0.000 claims description 4
JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 claims description 4
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 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
206010039966 Senile dementia Diseases 0.000 claims description 3
208000006673 asthma Diseases 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 3
208000017169 kidney disease Diseases 0.000 claims description 3
230000004973 motor coordination Effects 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
208000019116 sleep disease Diseases 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000007786 learning performance Effects 0.000 claims description 2
230000007334 memory performance Effects 0.000 claims description 2
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 14
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims 1
208000020358 Learning disease Diseases 0.000 claims 1
208000026139 Memory disease Diseases 0.000 claims 1
230000007850 degeneration Effects 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
201000003723 learning disability Diseases 0.000 claims 1
238000000034 method Methods 0.000 abstract description 54
230000008569 process Effects 0.000 abstract description 12
239000000126 substance Substances 0.000 abstract description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 104
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
238000005160 1H NMR spectroscopy Methods 0.000 description 53
238000010586 diagram Methods 0.000 description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
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LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000003518 presynaptic effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000008327 renal blood flow Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
239000003169 respiratory stimulant agent Substances 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000028327 secretion Effects 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000000946 synaptic effect Effects 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
235000012976 tarts Nutrition 0.000 description 1
RKSOPLXZQNSWAS-UHFFFAOYSA-N tert-butyl bromide Chemical compound CC(C)(C)Br RKSOPLXZQNSWAS-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical group CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
230000002537 thrombolytic effect Effects 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
150000008648 triflates Chemical class 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002242097A 1996-07-20 1998-06-26 Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques Expired - Fee Related CA2242097C (fr)

Priority Applications (34)

Application Number	Priority Date	Filing Date	Title
DE19629378A DE19629378A1 (de)	1996-07-20	1996-07-20	Neue Triazolopurine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
PT97933683T PT880524E (pt)	1996-07-20	1997-07-17	Antagonistas de adenosina processo para a sua preparacao e sua utilizacao como medicamentos
SK1144-98A SK114498A3 (en)	1996-07-20	1997-07-17	Imidazo triazolo pyrimidinone derivatives, method of preparing them and their use
HU9902311A HUP9902311A3 (en)	1996-07-20	1997-07-17	New triazolopurines, method of preparing them and their use as drugs
ZA976331A ZA976331B (en)	1996-07-20	1997-07-17	New imidazotriazolopyrimidines processes for their preparation and their use as pharmaceutical compositions
JP10505626A JP3020281B2 (ja)	1996-07-20	1997-07-17	新規なトリアゾロプリン類、その調製方法及び医薬組成物としての使用
EP97933683A EP0880524B1 (fr)	1996-07-20	1997-07-17	Antagonistes d'adenosine, procede pour les preparer et leur utilisation comme medicaments
IL12645397A IL126453A0 (en)	1996-07-20	1997-07-17	New triazolopurines method of preparing them and their use as drugs
EP99119410A EP0978517A3 (fr)	1996-07-20	1997-07-17	Triszolopurines, procédé pour leur préparation et leur application comme médicaments
EE9800451A EE9800451A (et)	1996-07-20	1997-07-17	Uued imidasotriasolopürimidiinid, nende valmistamismeetod ja kasutamine ravimainetena
CZ982654A CZ265498A3 (cs)	1996-07-20	1997-07-17	Triazolové deriváty, způsob jejich výroby a farmaceutický prostředek s jejich obsahem
PL97328824A PL328824A1 (en)	1996-07-20	1997-07-17	Novel triazolopurines, method of obtaining them and their application as drugs
ES97933683T ES2147453T3 (es)	1996-07-20	1997-07-17	Antagonistas de adenosina, procedimiento para su preparacion y su uso como medicamentos.
PCT/EP1997/003841 WO1998003511A1 (fr)	1996-07-20	1997-07-17	Nouvelles triazolopurines, procede pour les preparer et leur utilisation comme medicaments
CA002256736A CA2256736A1 (fr)	1996-07-20	1997-07-17	Nouvelles triazolopurines, procede pour les preparer et leur utilisation comme medicaments
CN97194506A CN1219936A (zh)	1996-07-20	1997-07-17	新的三唑并嘌呤、其制备方法及其作为药品的用途
DE59701467T DE59701467D1 (de)	1996-07-20	1997-07-17	Adenosin-antagonisten, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
BR9710747A BR9710747A (pt)	1996-07-20	1997-07-17	Novas triazolopurinas processos para a sua prepara-Æo e seu emprego como medicamento
TR1998/01659T TR199801659T2 (xx)	1996-07-20	1997-07-17	Yeni triazolopurinler, haz�rlama y�ntemi, ila� olarak kullan�m�.
DK97933683T DK0880524T3 (da)	1996-07-20	1997-07-17	Adenosinantagonister, fremgangsmåde til fremstilling deraf og deres anvendelse som medikamenter
AT97933683T ATE191913T1 (de)	1996-07-20	1997-07-17	Adenosin-antagonisten, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
AU36955/97A AU3695597A (en)	1996-07-20	1997-07-17	New triazolopurines, method of preparing them and their use as drugs
HR19629378.2A HRP970395A2 (en)	1996-07-20	1997-07-18	New triazolopurines, method for preparing them and their use as drugs
IDP972495A ID19106A (id)	1996-07-20	1997-07-18	Senyawa-senyawa triazolopurina baru dan proses-proses pembuatannya serta penggunaannya sebagai komposisi farmasi
CA002242097A CA2242097C (fr)	1996-07-20	1998-06-26	Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques
BG102707A BG102707A (bg)	1996-07-20	1998-08-20	Нови триазолопурини, метод за тяхното получаване и тяхното приложение като лекарствени средства
NO983860A NO983860L (no)	1996-07-20	1998-08-21	Nye triazolopuriner, fremgangsmÕte for deres fremstilling og deres anvendelse som legemidler
ZA9808189A ZA988189B (en)	1998-06-25	1998-09-08	New imidazotriazolopyrimidines, processes for preparing them and their use as pharmaceutical compositions.
PL98329578A PL329578A1 (en)	1998-06-25	1998-11-06	Derivatives of imidazotriazolepyrimidine, method of obtaining them and their application as drugs
BR9900187-0A BR9900187A (pt)	1998-06-25	1999-01-27	Novas imidazotriazolpirimidinonas, processo para a sua preparação e seu emprego como medicamento
AU17418/99A AU1741899A (en)	1996-07-20	1999-02-19	New imidazotriazolopyrimidinones, processes for preparing them and their use as pharmaceutical compositions
IDP990618D ID23607A (id)	1998-06-25	1999-06-25	Imidazotriazolopirimidinon, proses pembuatannya dan penggunaannya sebagai komposisi sediaan farmasi
US09/559,806 US6492377B1 (en)	1998-06-25	2000-04-26	Imidazotriazolopyrimidines with adenosine-antagonistic activity
GR20000401543T GR3033842T3 (en)	1996-07-20	2000-06-30	New triazolopurines, method of preparing them and their use as drugs

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE19629378A DE19629378A1 (de)	1996-07-20	1996-07-20	Neue Triazolopurine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
AU36955/97A AU3695597A (en)	1996-07-20	1997-07-17	New triazolopurines, method of preparing them and their use as drugs
US9058798P	1998-06-25	1998-06-25
CA002242097A CA2242097C (fr)	1996-07-20	1998-06-26	Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques

Publications (2)

Publication Number	Publication Date
CA2242097A1 CA2242097A1 (fr)	1999-12-26
CA2242097C true CA2242097C (fr)	2003-05-13

Family

ID=32966498

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002242097A Expired - Fee Related CA2242097C (fr)	1996-07-20	1998-06-26	Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques

Country Status (1)

Country	Link
CA (1)	CA2242097C (fr)

1998
- 1998-06-26 CA CA002242097A patent/CA2242097C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2242097A1 (fr)	1999-12-26

Legal Events

Date	Code	Title	Description
2001-05-03	EEER	Examination request
2013-08-07	MKLA	Lapsed	Effective date: 20130626

Publication	Publication Date	Title
US5719279A (en)	1998-02-17	Asymmetrically substituted xanthines
AU777571B2 (en)	2004-10-21	8-phenyl-6,9-dihydro-(1,2,4)triazolo(3,4-i)purin-5-one derivatives
EP1421084B1 (fr)	2008-05-14	Inhibiteurs polycycliques de la phosphodiesterase v de la guanine
KR101478368B1 (ko)	2014-12-31	유기 화합물
US6187780B1 (en)	2001-02-13	Assymetrically substituted xanthine derivatives having adenosine A1 antagonistic activity
CZ342595A3 (en)	1996-08-14	Purine derivatives, process of their preparation and pharmaceutical compositions containing thereof
CA2256736A1 (fr)	1998-01-29	Nouvelles triazolopurines, procede pour les preparer et leur utilisation comme medicaments
CA2328264A1 (fr)	1999-10-28	Nouveaux derives de xanthine a substitution asymetrique, leur procede de preparation et leur utilisation comme medicaments a effet antagoniste de l'adenosine
EP3735413B1 (fr)	2022-07-06	Composés tricycliques, compositions et leurs applications médicinales
CA2242097C (fr)	2003-05-13	Imidazotriazolopyrimidines, procedes pour les preparer, et leur utilisation en tant que compositions pharmaceutiques
US6492377B1 (en)	2002-12-10	Imidazotriazolopyrimidines with adenosine-antagonistic activity
HU223466B1 (hu)	2004-07-28	Allergia elleni imidazo[1,2a]tieno[2,3-d]azepin-származékok, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
CA2327395C (fr)	2008-05-13	Nouveaux imidazotriazolopyrimidines, procede pour les preparer et leur utilisation en tant que compositions pharmaceutiques
KR20000064893A (ko)	2000-11-06	트리아졸로퓨린,이의제조방법및이를함유하는약제학적제제
AU1741899A (en)	1999-06-17	New imidazotriazolopyrimidinones, processes for preparing them and their use as pharmaceutical compositions
WO2003043637A1 (fr)	2003-05-30	Derives de 3,7-dihydro-purine-2,6-dione utilises comme ligands du recepteur de crf
HK40040883A (en)	2021-08-06	Tricyclic compounds, compositions and medicinal applications thereof
HK1064668B (en)	2008-12-24	Polycyclic guanine phosphodiesterase v inhibitors
EP1790652A1 (fr)	2007-05-30	Guanines polycycliques comme inhibiteurs de la phosphodiésterase V
MXPA00009737A (en)	2001-07-31	Novel asymmetrically substituted xanthine derivatives, method for producing them and their use as medicaments with an adenosine-antagonistic effect