NO310292B1 - Pyrazolpyrimidiner - Google Patents

Pyrazolpyrimidiner Download PDF

Info

Publication number: NO310292B1
Authority: NO; Norway
Prior art keywords: alkyl; formula; compounds; hydroxy; compound
Prior art date: 1996-02-07

Application number

NO19981357A

Other languages

English (en)

Norwegian (no)

Other versions

NO981357D0 (no

NO981357L (no

Inventor

Chen Chen

Terence J Moran

James R Mccarthy

Keith M Wilcoxen

Thomas R Webb

Charles Huang

Original Assignee

Janssen Pharmaceutica Nv

Neurocrine Biosciences Inc

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.)

1996-02-07

Filing date

1998-03-25

Publication date

2001-06-18

1998-03-25 Application filed by Janssen Pharmaceutica Nv, Neurocrine Biosciences Inc filed Critical Janssen Pharmaceutica Nv

1998-03-25 Publication of NO981357D0 publication Critical patent/NO981357D0/no

1998-08-03 Publication of NO981357L publication Critical patent/NO981357L/no

2001-06-18 Publication of NO310292B1 publication Critical patent/NO310292B1/no

Links

150000001875 compounds Chemical class 0.000 claims description 102
239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 49
108010022152 Corticotropin-Releasing Hormone Proteins 0.000 claims description 48
102000012289 Corticotropin-Releasing Hormone Human genes 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 38
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 29
-1 homopiperidinyl group Chemical group 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
238000000034 method Methods 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
150000003839 salts Chemical group 0.000 claims description 15
125000001424 substituent group Chemical group 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 8
239000012442 inert solvent Substances 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
239000000460 chlorine Chemical group 0.000 claims description 6
239000013067 intermediate product Substances 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
239000002585 base Substances 0.000 claims description 5
229910052801 chlorine Chemical group 0.000 claims description 5
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000005905 mesyloxy group Chemical group 0.000 claims description 4
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
CRKVOYZFPHXADQ-UHFFFAOYSA-N 5-methyl-3-phenyl-7-phenylmethoxypyrazolo[1,5-a]pyrimidine Chemical compound N12N=CC(C=3C=CC=CC=3)=C2N=C(C)C=C1OCC1=CC=CC=C1 CRKVOYZFPHXADQ-UHFFFAOYSA-N 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
239000012458 free base Substances 0.000 claims description 3
ZECSJWNWZNAGGW-UHFFFAOYSA-N n,2,5-trimethyl-3-phenylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(NC)=CC(C)=NC2=C1C1=CC=CC=C1 ZECSJWNWZNAGGW-UHFFFAOYSA-N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
230000004962 physiological condition Effects 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
230000009466 transformation Effects 0.000 claims description 3
ANNRUWYFVIGKHA-UHFFFAOYSA-N 3-[6-(dimethylamino)-4-methylpyridin-3-yl]-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=CN=C(N(C)C)C=C1C ANNRUWYFVIGKHA-UHFFFAOYSA-N 0.000 claims description 2
QJEURMFEYXHROW-UHFFFAOYSA-N 3-[6-(dimethylamino)pyridin-3-yl]-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical group CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=CC=C(N(C)C)N=C1 QJEURMFEYXHROW-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
239000003513 alkali Substances 0.000 claims 2
239000000126 substance Substances 0.000 claims 2
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
239000000243 solution Substances 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 28
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
239000000543 intermediate Substances 0.000 description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
230000000694 effects Effects 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000002769 corticotropin releasing factor antagonist Substances 0.000 description 14
208000035475 disorder Diseases 0.000 description 14
241001465754 Metazoa Species 0.000 description 13
238000012360 testing method Methods 0.000 description 13
230000027455 binding Effects 0.000 description 12
229940044551 receptor antagonist Drugs 0.000 description 12
239000002464 receptor antagonist Substances 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 10
238000003556 assay Methods 0.000 description 9
201000010099 disease Diseases 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
230000006399 behavior Effects 0.000 description 8
230000002124 endocrine Effects 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 8
108020003175 receptors Proteins 0.000 description 8
102000005962 receptors Human genes 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000007787 solid Substances 0.000 description 8
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
102100027467 Pro-opiomelanocortin Human genes 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
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
102000030621 adenylate cyclase Human genes 0.000 description 6
108060000200 adenylate cyclase Proteins 0.000 description 6
239000005557 antagonist Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
241000700159 Rattus Species 0.000 description 5
229940126545 compound 53 Drugs 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
108090000765 processed proteins & peptides Proteins 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
208000019901 Anxiety disease Diseases 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
230000000949 anxiolytic effect Effects 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
239000012267 brine Substances 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
239000003446 ligand Substances 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
238000012746 preparative thin layer chromatography Methods 0.000 description 4
102000004196 processed proteins & peptides Human genes 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
239000002287 radioligand Substances 0.000 description 4
229930195734 saturated hydrocarbon Natural products 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 3
JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
208000000103 Anorexia Nervosa Diseases 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
101800000414 Corticotropin Proteins 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
108010069820 Pro-Opiomelanocortin Proteins 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
239000000654 additive Substances 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
230000003042 antagnostic effect Effects 0.000 description 3
230000002180 anti-stress Effects 0.000 description 3
230000036506 anxiety Effects 0.000 description 3
239000002249 anxiolytic agent Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 3
229960000258 corticotropin Drugs 0.000 description 3
108010050742 corticotropin releasing hormone (9-41) Proteins 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000000185 intracerebroventricular administration Methods 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
238000000926 separation method Methods 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000007910 systemic administration Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
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CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
208000032841 Bulimia Diseases 0.000 description 2
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OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
208000017701 Endocrine disease Diseases 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
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206010020772 Hypertension Diseases 0.000 description 2
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TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
208000019022 Mood disease Diseases 0.000 description 2
238000007126 N-alkylation reaction Methods 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 2
208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 2
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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Health & Medical Sciences (AREA)
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Medicinal Chemistry (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
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Immunology (AREA)
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Biomedical Technology (AREA)
Pulmonology (AREA)
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Diabetes (AREA)
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Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Transplantation (AREA)
Nutrition Science (AREA)
Urology & Nephrology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
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NO19981357A 1996-02-07 1998-03-25 Pyrazolpyrimidiner NO310292B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US1127996P	1996-02-07	1996-02-07
US2768896P	1996-10-08	1996-10-08
PCT/EP1997/000459 WO1997029109A1 (en)	1996-02-07	1997-01-30	Pyrazolopyrimidines as crf receptor antagonists

Publications (3)

Publication Number	Publication Date
NO981357D0 NO981357D0 (no)	1998-03-25
NO981357L NO981357L (no)	1998-08-03
NO310292B1 true NO310292B1 (no)	2001-06-18

Family

ID=26682204

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981357A NO310292B1 (no)	1996-02-07	1998-03-25	Pyrazolpyrimidiner

Country Status (27)

Country	Link
EP (1)	EP0880523B1 (hu)
JP (2)	JP3356291B2 (hu)
KR (1)	KR100421626B1 (hu)
CN (1)	CN1090189C (hu)
AR (1)	AR008577A1 (hu)
AT (1)	ATE336495T1 (hu)
AU (1)	AU713673B2 (hu)
BG (1)	BG102349A (hu)
BR (1)	BR9707391A (hu)
CA (1)	CA2233285C (hu)
CZ (1)	CZ244598A3 (hu)
DE (2)	DE880523T1 (hu)
DK (1)	DK0880523T3 (hu)
EA (1)	EA000803B1 (hu)
EE (1)	EE04282B1 (hu)
ES (1)	ES2168237T3 (hu)
HU (1)	HUP9900575A3 (hu)
ID (1)	ID15905A (hu)
IL (1)	IL123835A0 (hu)
NO (1)	NO310292B1 (hu)
NZ (1)	NZ330119A (hu)
PL (1)	PL191271B1 (hu)
PT (1)	PT880523E (hu)
SK (1)	SK106398A3 (hu)
TR (1)	TR199800792T2 (hu)
TW (1)	TW449599B (hu)
WO (1)	WO1997029109A1 (hu)

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TWI271406B (en)	1999-12-13	2007-01-21	Eisai Co Ltd	Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same
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TWI312347B (en)	2001-02-08	2009-07-21	Eisai R&D Man Co Ltd	Bicyclic nitrogen-containing condensed ring compounds
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1997
- 1997-01-30 CN CN97191382A patent/CN1090189C/zh not_active Expired - Fee Related
- 1997-01-30 EE EE9800124A patent/EE04282B1/xx not_active IP Right Cessation
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- 1997-01-30 KR KR10-1998-0703401A patent/KR100421626B1/ko not_active Expired - Fee Related
- 1997-01-30 HU HU9900575A patent/HUP9900575A3/hu unknown
- 1997-01-30 DE DE0880523T patent/DE880523T1/de active Pending
- 1997-01-30 EP EP97902295A patent/EP0880523B1/en not_active Expired - Lifetime
- 1997-01-30 BR BR9707391A patent/BR9707391A/pt not_active Application Discontinuation
- 1997-01-30 EA EA199800394A patent/EA000803B1/ru not_active IP Right Cessation
- 1997-01-30 CZ CZ982445A patent/CZ244598A3/cs unknown
- 1997-01-30 IL IL12383597A patent/IL123835A0/xx active IP Right Grant
- 1997-01-30 SK SK1063-98A patent/SK106398A3/sk unknown
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- 1997-01-30 AU AU15991/97A patent/AU713673B2/en not_active Ceased
- 1997-01-30 DK DK97902295T patent/DK0880523T3/da active
- 1997-01-30 AT AT97902295T patent/ATE336495T1/de active
- 1997-01-30 PT PT97902295T patent/PT880523E/pt unknown
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- 1997-01-30 WO PCT/EP1997/000459 patent/WO1997029109A1/en not_active Ceased
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Also Published As

Publication number	Publication date
EE04282B1 (et)	2004-04-15
AU1599197A (en)	1997-08-28
DK0880523T3 (da)	2007-03-26
WO1997029109A1 (en)	1997-08-14
DE880523T1 (de)	2002-07-04
CA2233285C (en)	2006-07-04
EP0880523A1 (en)	1998-12-02
EA199800394A1 (ru)	1998-10-29
NO981357D0 (no)	1998-03-25
BR9707391A (pt)	1999-07-20
KR100421626B1 (ko)	2004-05-20
JP2000503661A (ja)	2000-03-28
ATE336495T1 (de)	2006-09-15
SK106398A3 (en)	1998-12-02
JP2002121194A (ja)	2002-04-23
HUP9900575A3 (en)	2001-11-28
TW449599B (en)	2001-08-11
CA2233285A1 (en)	1997-08-14
EP0880523B1 (en)	2006-08-16
DE69736513T2 (de)	2007-04-05
KR19990067391A (ko)	1999-08-16
ES2168237T1 (es)	2002-06-16
ES2168237T3 (es)	2007-04-01
EA000803B1 (ru)	2000-04-24
NO981357L (no)	1998-08-03
ID15905A (id)	1997-08-14
BG102349A (en)	1999-02-26
PL327284A1 (en)	1998-12-07
CZ244598A3 (cs)	1998-10-14
JP3356291B2 (ja)	2002-12-16
AU713673B2 (en)	1999-12-09
CN1090189C (zh)	2002-09-04
AR008577A1 (es)	2000-02-09
IL123835A0 (en)	1998-10-30
DE69736513D1 (de)	2006-09-28
PT880523E (pt)	2007-01-31
EE9800124A (et)	1998-10-15
PL191271B1 (pl)	2006-04-28
CN1205009A (zh)	1999-01-13
HUP9900575A2 (hu)	1999-06-28
NZ330119A (en)	2000-02-28
TR199800792T2 (xx)	1998-07-21

Publication	Publication Date	Title
NO310292B1 (no)	2001-06-18	Pyrazolpyrimidiner
US6255310B1 (en)	2001-07-03	Thiophenopyrimidines
US6352990B1 (en)	2002-03-05	CRF receptor antagonists and methods relating thereto
NL1026030C2 (nl)	2005-07-05	Cannabinoïdreceptorliganden en toepassingen daarvan.
US6664261B2 (en)	2003-12-16	Pyrazolopyrimidines as CRF receptor antagonists
NL1026029C2 (nl)	2005-07-05	Cannabinoïdreceptorliganden en toepassingen daarvan.
US20140206662A1 (en)	2014-07-24	Imidazopyridine Compounds
PL200939B1 (pl)	2009-02-27	Związki [1,5-a]-pirazolo-1,3,5-triazynowe, środek farmaceutyczny i zastosowanie tych związków
EP0863882B1 (en)	2002-02-06	Amino substituted pyrimidines and triazines
US6613777B1 (en)	2003-09-02	CRF antagonistic pyrazolo[4,3-b]pyridines
MXPA98003167A (en)	1999-07-06	Pirazolopirimidinas with antagonist properties of the corticotropin release factor receptor (crf) and pharmaceutical compositions that contain them
IL123835A (en)	2006-09-05	3 - ARYL - 5, 7 - DISUBSTITUTED PYRAZOLO [1,5-a] - PYRIMIDINE DERIVATIVES, THEIR USE AS CRF RECEPTOR ANTAGONIST, THEIR PREPARTION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
HK1012189B (en)	2002-05-10	Amino substituted pyrimidines and triazines
HK1012189A1 (en)	1999-07-30	Amino substituted pyrimidines and triazines

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