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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
206010002388 Angina unstable Diseases 0.000 description 2
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
206010006550 Bulimia nervosa Diseases 0.000 description 2
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
101000895481 Homo sapiens Corticoliberin Proteins 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
206010062016 Immunosuppression Diseases 0.000 description 2
206010021750 Infantile Spasms Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
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
229920012196 Polyoxymethylene Copolymer Polymers 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000007814 Unstable Angina Diseases 0.000 description 2
201000006791 West syndrome Diseases 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
230000016571 aggressive behavior Effects 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000002260 anti-inflammatory agent Substances 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
230000000338 anxiogenic effect Effects 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
GBONBLHJMVUBSJ-FAUHKOHMSA-N corticorelin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)C1=CNC=N1 GBONBLHJMVUBSJ-FAUHKOHMSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
210000000750 endocrine system Anatomy 0.000 description 2
206010015037 epilepsy Diseases 0.000 description 2
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
210000000987 immune system Anatomy 0.000 description 2
230000001506 immunosuppresive effect Effects 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
201000004332 intermediate coronary syndrome Diseases 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
208000002551 irritable bowel syndrome Diseases 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000002609 medium Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000000926 neurological effect Effects 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
208000019906 panic disease Diseases 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
229960003415 propylparaben Drugs 0.000 description 2
238000000159 protein binding assay Methods 0.000 description 2
208000020016 psychiatric disease Diseases 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000003653 radioligand binding assay Methods 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
239000000932 sedative agent Substances 0.000 description 2
230000001624 sedative effect Effects 0.000 description 2
239000013049 sediment Substances 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
201000009032 substance abuse Diseases 0.000 description 2
231100000736 substance abuse Toxicity 0.000 description 2
208000011117 substance-related disease Diseases 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
210000000225 synapse Anatomy 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
VPSSPAXIFBTOHY-ZCFIWIBFSA-N (2r)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@@H](N)CO VPSSPAXIFBTOHY-ZCFIWIBFSA-N 0.000 description 1
NEYDFEJOMAZBBF-AWEZNQCLSA-N (2s)-2-[[3-(2,4-dichlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1=NN2C(N[C@H](CO)CC(C)C)=CC(C)=NC2=C1C1=CC=C(Cl)C=C1Cl NEYDFEJOMAZBBF-AWEZNQCLSA-N 0.000 description 1
VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
ZKSRIPVNRIUEOM-UHFFFAOYSA-N 1,2-dihydropyrazolo[4,3-d]pyrimidin-3-one Chemical class N1=CN=C2C(O)=NNC2=C1 ZKSRIPVNRIUEOM-UHFFFAOYSA-N 0.000 description 1
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 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
LOUGYXZSURQALL-UHFFFAOYSA-N 2,3-dihydroxybutanoic acid Chemical compound CC(O)C(O)C(O)=O LOUGYXZSURQALL-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
IQFYBOHTMVGWBU-UHFFFAOYSA-N 2-[6-(dimethylamino)pyridin-3-yl]acetonitrile Chemical compound CN(C)C1=CC=C(CC#N)C=N1 IQFYBOHTMVGWBU-UHFFFAOYSA-N 0.000 description 1
FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
JCQCHFSCTQUACQ-UHFFFAOYSA-N 2-[benzyl-[3-(2,4-dichlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-yl]amino]ethyl acetate Chemical compound C=1C(C)=NC2=C(C=3C(=CC(Cl)=CC=3)Cl)C=NN2C=1N(CCOC(=O)C)CC1=CC=CC=C1 JCQCHFSCTQUACQ-UHFFFAOYSA-N 0.000 description 1
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
125000006024 2-pentenyl group Chemical group 0.000 description 1
LYTMBAHVTWZOMX-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-7-ethoxy-5-methyl-2-methylsulfanylpyrazolo[1,5-a]pyrimidine Chemical compound CSC1=NN2C(OCC)=CC(C)=NC2=C1C1=CC=C(Cl)C=C1Cl LYTMBAHVTWZOMX-UHFFFAOYSA-N 0.000 description 1
JKUFFNFWFPLHLU-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-n-(3-methoxypropyl)-5-methyl-n-propylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C1=NN2C(N(CCCOC)CCC)=CC(C)=NC2=C1C1=CC=C(Cl)C=C1Cl JKUFFNFWFPLHLU-UHFFFAOYSA-N 0.000 description 1
DOPVGJROKFQOTD-UHFFFAOYSA-N 3-(4-chlorophenyl)-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=CC=C(Cl)C=C1 DOPVGJROKFQOTD-UHFFFAOYSA-N 0.000 description 1
MBANSLYUPGYBGU-UHFFFAOYSA-N 3-(5-amino-3-methylpyridin-2-yl)-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=NC=C(N)C=C1C MBANSLYUPGYBGU-UHFFFAOYSA-N 0.000 description 1
BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 1
AVIYBZJGACSQAF-UHFFFAOYSA-N 3-[5-(dimethylamino)-3-methylpyridin-2-yl]-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=NC=C(N(C)C)C=C1C AVIYBZJGACSQAF-UHFFFAOYSA-N 0.000 description 1
LGDDPMVPDGTXMV-UHFFFAOYSA-N 3-[6-(dimethylamino)-4-methylpyridin-3-yl]-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine;hydrochloride Chemical compound Cl.CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=CN=C(N(C)C)C=C1C LGDDPMVPDGTXMV-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
CZIQMRKVTJZNBJ-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-1h-pyrazol-5-amine Chemical compound NC1=NNC=C1C1=CC=C(Cl)C=C1Cl CZIQMRKVTJZNBJ-UHFFFAOYSA-N 0.000 description 1
WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
UTGWJSYDUVHYIV-UHFFFAOYSA-N 5-(7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-n,n-dimethylpyridin-2-amine Chemical compound C1=NC(N(C)C)=CC=C1C1=C2N=C(C)C=C(Cl)N2N=C1C UTGWJSYDUVHYIV-UHFFFAOYSA-N 0.000 description 1
WLIQXUZVQKMECQ-UHFFFAOYSA-N 5-butyl-3-(2,4-dichlorophenyl)-n-(3-methoxypropyl)-n-propylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound C=12N=C(CCCC)C=C(N(CCC)CCCOC)N2N=CC=1C1=CC=C(Cl)C=C1Cl WLIQXUZVQKMECQ-UHFFFAOYSA-N 0.000 description 1
ILCVKEBXPLEGOY-ZLFMSJRASA-N 74434-59-6 Chemical compound CC[C@H](C)[C@@H](C(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)CNC(=O)[C@H]2NC(=O)CC2)CCC1 ILCVKEBXPLEGOY-ZLFMSJRASA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000000275 Adrenocorticotropic Hormone Substances 0.000 description 1
208000007848 Alcoholism Diseases 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
101800005049 Beta-endorphin Proteins 0.000 description 1
VZDDWKRIAOIHKX-UHFFFAOYSA-N C1=NC(N(C)C)=CC=C1C1=C2N=C(C)C=C(O)N2N=C1C Chemical compound C1=NC(N(C)C)=CC=C1C1=C2N=C(C)C=C(O)N2N=C1C VZDDWKRIAOIHKX-UHFFFAOYSA-N 0.000 description 1
XVQOIGHKPWCQRJ-UHFFFAOYSA-N C=12N=C(C)C=C(Cl)N2N=CC=1C1=CC=C(Cl)C=C1Cl Chemical compound C=12N=C(C)C=C(Cl)N2N=CC=1C1=CC=C(Cl)C=C1Cl XVQOIGHKPWCQRJ-UHFFFAOYSA-N 0.000 description 1
UBNLEMOWJYKXCG-UHFFFAOYSA-N C=12N=C(C)C=C(O)N2N=CC=1C1=CC=C(Cl)C=C1Cl Chemical compound C=12N=C(C)C=C(O)N2N=CC=1C1=CC=C(Cl)C=C1Cl UBNLEMOWJYKXCG-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
208000004652 Cardiovascular Abnormalities Diseases 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
229940126657 Compound 17 Drugs 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010013142 Disinhibition Diseases 0.000 description 1
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
208000030814 Eating disease Diseases 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
208000019454 Feeding and Eating disease Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
229910001335 Galvanized steel Inorganic materials 0.000 description 1
208000011688 Generalised anxiety disease Diseases 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
206010062767 Hypophysitis Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
125000000815 N-oxide group Chemical group 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
238000010934 O-alkylation reaction Methods 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000000683 Pro-Opiomelanocortin Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
235000002357 Ribes grossularia Nutrition 0.000 description 1
244000171263 Ribes grossularia Species 0.000 description 1
240000007651 Rubus glaucus Species 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
108010011107 Urotensins Proteins 0.000 description 1
102000026557 Urotensins Human genes 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
231100000230 acceptable toxicity Toxicity 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
210000004100 adrenal gland Anatomy 0.000 description 1
201000007930 alcohol dependence Diseases 0.000 description 1
125000005332 alkyl sulfoxy group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
DVHXJLRODLTJOD-UHFFFAOYSA-N aminoazanium;bromide Chemical compound Br.NN DVHXJLRODLTJOD-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
210000004727 amygdala Anatomy 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
230000009910 autonomic response Effects 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
239000000022 bacteriostatic agent Substances 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
WOPZMFQRCBYPJU-NTXHZHDSSA-N beta-endorphin Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CC=CC=C1 WOPZMFQRCBYPJU-NTXHZHDSSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000003851 biochemical process Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
230000003491 cAMP production Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
239000000969 carrier Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004891 communication Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940125851 compound 27 Drugs 0.000 description 1
229940125844 compound 46 Drugs 0.000 description 1
229940127113 compound 57 Drugs 0.000 description 1
238000004590 computer program Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229940075894 denatured ethanol Drugs 0.000 description 1
238000011161 development Methods 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
235000014632 disordered eating Nutrition 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000003826 endocrine responses Effects 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000004744 fabric Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
230000006870 function Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000008397 galvanized steel Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
208000029364 generalized anxiety disease Diseases 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
230000000147 hypnotic effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000036737 immune function Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000010354 integration Effects 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
239000007788 liquid Substances 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
210000000627 locus coeruleus Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
238000005259 measurement Methods 0.000 description 1
108020004084 membrane receptors Proteins 0.000 description 1
102000006240 membrane receptors Human genes 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
230000004899 motility Effects 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
XQWSZCBQDOKMBX-UHFFFAOYSA-N n-methylpyrazolo[1,5-a]pyrimidin-7-amine Chemical class CNC1=CC=NC2=CC=NN12 XQWSZCBQDOKMBX-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
230000002474 noradrenergic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940100688 oral solution Drugs 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
QEEJLLNYQOBRRM-KSHGRFHLSA-N ovine crf Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CN=CN1 QEEJLLNYQOBRRM-KSHGRFHLSA-N 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
230000036284 oxygen consumption Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
108700029059 phenylalanyl corticotropin-releasing factor (12-41) Proteins 0.000 description 1
230000006461 physiological response Effects 0.000 description 1
230000001817 pituitary effect Effects 0.000 description 1
210000003635 pituitary gland Anatomy 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940068918 polyethylene glycol 400 Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
150000004944 pyrrolopyrimidines Chemical class 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
230000009257 reactivity Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000003938 response to stress Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 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
229960004889 salicylic acid Drugs 0.000 description 1
108010086511 sauvagine Proteins 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
230000009329 sexual behaviour Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000007974 sodium acetate buffer Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000001958 sympathoadrenomedullary effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
239000000780 urotensin Substances 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003064 xanthine oxidase inhibitor 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/02—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 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems

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 (de)
JP (2)	JP3356291B2 (de)
KR (1)	KR100421626B1 (de)
CN (1)	CN1090189C (de)
AR (1)	AR008577A1 (de)
AT (1)	ATE336495T1 (de)
AU (1)	AU713673B2 (de)
BG (1)	BG102349A (de)
BR (1)	BR9707391A (de)
CA (1)	CA2233285C (de)
CZ (1)	CZ244598A3 (de)
DE (2)	DE69736513T2 (de)
DK (1)	DK0880523T3 (de)
EA (1)	EA000803B1 (de)
EE (1)	EE04282B1 (de)
ES (1)	ES2168237T3 (de)
HU (1)	HUP9900575A3 (de)
ID (1)	ID15905A (de)
IL (1)	IL123835A0 (de)
NO (1)	NO310292B1 (de)
NZ (1)	NZ330119A (de)
PL (1)	PL191271B1 (de)
PT (1)	PT880523E (de)
SK (1)	SK106398A3 (de)
TR (1)	TR199800792T2 (de)
TW (1)	TW449599B (de)
WO (1)	WO1997029109A1 (de)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6060478A (en) *	1996-07-24	2000-05-09	Dupont Pharmaceuticals	Azolo triazines and pyrimidines
US7094782B1 (en)	1996-07-24	2006-08-22	Bristol-Myers Squibb Company	Azolo triazines and pyrimidines
US6191131B1 (en)	1997-07-23	2001-02-20	Dupont Pharmaceuticals Company	Azolo triazines and pyrimidines
US6124289A (en) *	1996-07-24	2000-09-26	Dupont Pharmaceuticals Co.	Azolo triazines and pyrimidines
RO121272B1 (ro) *	1996-07-24	2007-02-28	The Du Pont Merck Pharmaceutical Company	Azolotriazine şi pirimidine
US6313124B1 (en)	1997-07-23	2001-11-06	Dupont Pharmaceuticals Company	Tetrazine bicyclic compounds
KR20000029843A (ko)	1996-08-06	2000-05-25	디. 제이. 우드;스피겔 알렌 제이	치환된피리도-또는피리미도-함유6,6-또는6,7-비시클릭유도체
US5723608A (en)	1996-12-31	1998-03-03	Neurogen Corporation	3-aryl substituted pyrazolo 4,3-d!pyrimidine derivatives; corticotropin-releasing factor receptor (CRF1) specific ligands
EP0970082A2 (de)	1997-02-18	2000-01-12	Neurocrine Biosciences, Inc.	Biazazyklische crf antagonisten
US6235741B1 (en) *	1997-05-30	2001-05-22	Merck & Co., Inc.	Angiogenesis inhibitors
JP2002501532A (ja) *	1997-05-30	2002-01-15	メルクエンドカンパニーインコーポレーテッド	新規血管形成阻害薬
NL1010018C2 (nl) *	1997-09-09	1999-03-10	Duphar Int Res	Chinoline en chinazoline derivaten met corticotropine releasing factor (CRF) antagonistische werking.
US6380203B1 (en)	1998-01-14	2002-04-30	Merck & Co., Inc.	Angiogenesis inhibitors
NZ505079A (en) *	1998-01-28	2003-08-29	Du Pont Pharm Co	Pyrazolotriazines and pyrazolopyrimidines useful as corticotropin releasing factor antagonists
US6613777B1 (en)	1998-03-06	2003-09-02	Chen Chen	CRF antagonistic pyrazolo[4,3-b]pyridines
WO1999051597A1 (en)	1998-04-02	1999-10-14	Neurogen Corporation	Aminoalkyl substituted 5,6,7,8-tetrahydro-9h pyrimidino[2,3-b]indole and 5,6,7,8-tetrahydro-9h-pyrimidino[4,5-b]indole derivatives: crf1 specific ligands
US6472402B1 (en)	1998-04-02	2002-10-29	Neurogen Corporation	Aminoalkyl substituted 5,6,7,8-Tetrahydro-9H-Pyridino [2,3-B]indole derivatives
EP1149835A4 (de) *	1999-01-29	2002-08-21	Sumitomo Chemical Co	Agentien zur hemmung der fettansammlung
AU4203500A (en)	1999-04-06	2000-10-23	Du Pont Pharmaceuticals Company	Pyrazolopyrimidines as crf antagonists
WO2000059907A2 (en)	1999-04-06	2000-10-12	Du Pont Pharmaceuticals Company	Pyrazolotriazines as crf antagonists
US6432989B1 (en)	1999-08-27	2002-08-13	Pfizer Inc	Use of CRF antagonists to treat circadian rhythm disorders
YU23802A (sh)	1999-09-30	2004-09-03	Neurogen Corporation	Određeni alkilen diamin-supstituisani pirazolo/1,5-a/-1,5- piramidini i pirazolo/1,5-a/1,3,5-triazini
IL139197A0 (en)	1999-10-29	2001-11-25	Pfizer Prod Inc	Use of corticotropin releasing factor antagonists and related compositions
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
CA2398956A1 (en) *	2000-02-14	2001-08-16	Japan Tobacco Inc.	A pharmaceutical composition for prophylaxis or therapy of a postoperative stress
EP1359916A4 (de)	2001-01-26	2004-04-07	Bristol Myers Squibb Co	Imidazolylderivative als hemmer des corticotropin-releasing-faktors
TWI312347B (en)	2001-02-08	2009-07-21	Eisai R&D Man Co Ltd	Bicyclic nitrogen-containing condensed ring compounds
KR100876622B1 (ko) *	2001-04-27	2008-12-31	에자이 알앤드디 매니지먼트 가부시키가이샤	피라졸로[1,5-ａ]피리딘 화합물 및 그 의약
US6872827B2 (en)	2002-04-26	2005-03-29	Chembridge Research Laboratories, Inc.	Somatostatin analogue compounds
US7161003B1 (en) *	2002-09-04	2007-01-09	Schering Corporation	Pyrazolopyrimidines as cyclin dependent kinase inhibitors
US7176216B2 (en)	2002-10-22	2007-02-13	Eisai Co., Ltd.	7-phenylpyrazolopyridine compounds
ATE426600T1 (de)	2002-10-22	2009-04-15	Eisai R&D Man Co Ltd	7-phenylpyrazolopyridinverbindungen
DK1599468T3 (da)	2003-01-14	2008-02-04	Arena Pharm Inc	1,2,3-trisubstituerede aryl- og heteroarylderivater som modulatorer af metabolisme og forebyggelse og behandling af forstyrrelser forbundet dermed såsom diabetes og hyperglykæmi
EP1608652A1 (de) *	2003-03-31	2005-12-28	Vernalis (Cambridge) Limited	Pyrazolopyrimidinverbindungen und deren verwendung in der medizin
AR045047A1 (es)	2003-07-11	2005-10-12	Arena Pharm Inc	Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos
EP2287166A3 (de)	2003-07-14	2011-06-22	Arena Pharmaceuticals, Inc.	Kondensierte Aryl- und Heteroarylderivate als Modulatoren des Metabolismus sowie Vorbeugung und Behandlung von damit zusammenhängenden Störungen
US7329662B2 (en) *	2003-10-03	2008-02-12	Hoffmann-La Roche Inc.	Pyrazolo-pyridine
EP1697369A1 (de) *	2003-12-22	2006-09-06	SB Pharmco Puerto Rico Inc	Crf-rezeptorantagonisten und diese betreffende verfahren
CA2550948A1 (en) *	2003-12-22	2005-07-14	Sb Pharmco Puerto Rico Inc.	Crf receptor antagonists and methods relating thereto
US20070129382A1 (en) *	2004-02-13	2007-06-07	Dimitri Grigoriadis	Crf receptor antagonists, their preparations, their pharmaceutical composition, and their uses
GB0519957D0 (en)	2005-09-30	2005-11-09	Sb Pharmco Inc	Chemical compound
JP4708438B2 (ja)	2005-02-11	2011-06-22	エフ．ホフマン−ラロシュアーゲー	ｍＧｌｕＲ２アンタゴニストとしてのピラゾロピリミジン誘導体
ATE424402T1 (de) *	2005-03-21	2009-03-15	Lilly Co Eli	Imidazopyridinverbindungen
RU2412943C2 (ru)	2005-03-23	2011-02-27	Ф. Хоффманн-Ля Рош Аг	ПРОИЗВОДНЫЕ АЦЕТИЛЕНИЛ-ПИРАЗОЛО-ПИРИМИДИНА В КАЧЕСТВЕ АНТАГОНИСТОВ mGluR2
US7557103B2 (en)	2005-04-05	2009-07-07	Eli Lilly And Company	Imidazopyridazine compounds
WO2007017678A1 (en) *	2005-08-09	2007-02-15	Eirx Therapeutics Limited	Pyrazolo[1,5-a] pyrimidine compounds and pharmaceutical compositions containing them
ATE463495T1 (de)	2005-09-27	2010-04-15	Hoffmann La Roche	Oxadiazolylpyrazolopyrimidine als mglur2- antagonisten
MX2009003125A (es)	2006-09-20	2009-05-28	Lilly Co Eli	Tiazol pirazolopirimidinas como antagonistas de receptor de crf1.
CA2662000C (en)	2006-09-20	2013-01-08	Eli Lilly And Company	Thiophene pyrazolopyrimidine compounds
ATE522249T1 (de)	2007-07-26	2011-09-15	Novartis Ag	Organische verbindungen
ES2396126T3 (es)	2008-04-15	2013-02-19	Eisai R&D Management Co., Ltd.	Compuesto de 3-fenilpirazol[5,1-b]tiazol
AR078521A1 (es)	2009-10-08	2011-11-16	Eisai R&D Man Co Ltd	Compuesto pirazolotiazol
SG188548A1 (en)	2010-09-22	2013-04-30	Arena Pharm Inc	Modulators of the gpr119 receptor and the treatment of disorders related thereto
GB201210686D0 (en)	2012-06-15	2012-08-01	Holsboermaschmeyer Neurochemie Gmbh	V1B receptor antagonist for use in the treatment of patients having an elevated AVP level and/or an elevated copeptin level
GB201310782D0 (en)	2013-06-17	2013-07-31	Max Planck Innovation Gmbh	Method for predicting a treatment response to a CRHR1 antagonist and/or V1B antagonist in a patient with depressive and/or anxiety symptoms
EP3242666A1 (de)	2015-01-06	2017-11-15	Arena Pharmaceuticals, Inc.	Verfahren zur behandlung von erkrankungen im zusammenhang mit dem s1p1-rezeptor
PL236355B1 (pl) *	2015-04-02	2021-01-11	Celon Pharma Spolka Akcyjna	Pochodne 7-(morfolin-4-ylo)pirazolo[1,5-α]pirymidyny jako inhibitory kinazy PI3
JP6838744B2 (ja)	2015-06-22	2021-03-03	アリーナファーマシューティカルズ，インコーポレイテッド	Ｓ１Ｐ１レセプター関連障害における使用のための（Ｒ）−２−（７−（４−シクロペンチル−３−（トリフルオロメチル）ベンジルオキシ）−１，２，３，４−テトラヒドロシクロペンタ［ｂ］インドール−３−イル）酢酸（化合物１）の結晶性Ｌ−アルギニン塩
CN116478132A (zh)	2016-07-12	2023-07-25	锐新医药公司	作为变构shp2抑制剂的2,5-双取代型及2,5,6-三取代型3-甲基吡嗪
MX2019008696A (es)	2017-01-23	2019-09-13	Revolution Medicines Inc	Compuestos de piridina como inhibidores de shp2 alostericos.
MX2019008695A (es)	2017-01-23	2019-09-11	Revolution Medicines Inc	Compuestos biciclicos como inhibidores alostericos de shp2.
MX2019015318A (es) *	2017-08-14	2020-07-20	Spruce Biosciences Inc	Antagonistas del receptor del factor liberador de corticotropina.
CA3074690A1 (en)	2017-09-07	2019-03-14	Revolution Medicines, Inc.	Shp2 inhibitor compositions and methods for treating cancer
EP3694848A1 (de)	2017-10-12	2020-08-19	Revolution Medicines, Inc.	Pyridin-, pyrazin- und triazinverbindungen als allosterische shp2-inhibitoren
EP3724189B1 (de)	2017-12-15	2023-10-04	Revolution Medicines, Inc.	Polyzyklischen verbindungen als allosterischen shp2 hemmer
CA3188730A1 (en)	2020-08-12	2022-02-17	Christopher Barnes	Methods and compositions for treating polycystic ovary syndrome
US11708372B2 (en)	2021-11-19	2023-07-25	Spruce Biosciences, Inc.	Crystalline composition of tildacerfont and methods of use and preparation thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS4211753Y1 (de) *	1964-06-06	1967-06-30
JPS6157587A (ja) *	1984-08-29	1986-03-24	Shionogi & Co Ltd	縮合複素環誘導体および抗潰瘍剤
JPH0211753A (ja) *	1988-06-29	1990-01-16	Raimuzu:Kk	ＴｉＡｌ系複合部材及びその製造方法
TW444018B (en) *	1992-12-17	2001-07-01	Pfizer	Pyrazolopyrimidines

1997
- 1997-01-30 WO PCT/EP1997/000459 patent/WO1997029109A1/en active IP Right Grant
- 1997-01-30 PL PL327284A patent/PL191271B1/pl not_active IP Right Cessation
- 1997-01-30 EP EP97902295A patent/EP0880523B1/de not_active Expired - Lifetime
- 1997-01-30 CZ CZ982445A patent/CZ244598A3/cs unknown
- 1997-01-30 SK SK1063-98A patent/SK106398A3/sk unknown
- 1997-01-30 JP JP52812397A patent/JP3356291B2/ja not_active Expired - Fee Related
- 1997-01-30 BR BR9707391A patent/BR9707391A/pt not_active Application Discontinuation
- 1997-01-30 DE DE69736513T patent/DE69736513T2/de not_active Expired - Lifetime
- 1997-01-30 AU AU15991/97A patent/AU713673B2/en not_active Ceased
- 1997-01-30 TR TR1998/00792T patent/TR199800792T2/xx unknown
- 1997-01-30 NZ NZ330119A patent/NZ330119A/en not_active IP Right Cessation
- 1997-01-30 PT PT97902295T patent/PT880523E/pt unknown
- 1997-01-30 CN CN97191382A patent/CN1090189C/zh not_active Expired - Fee Related
- 1997-01-30 HU HU9900575A patent/HUP9900575A3/hu unknown
- 1997-01-30 KR KR10-1998-0703401A patent/KR100421626B1/ko not_active IP Right Cessation
- 1997-01-30 AT AT97902295T patent/ATE336495T1/de active
- 1997-01-30 CA CA002233285A patent/CA2233285C/en not_active Expired - Fee Related
- 1997-01-30 ES ES97902295T patent/ES2168237T3/es not_active Expired - Lifetime
- 1997-01-30 DE DE0880523T patent/DE880523T1/de active Pending
- 1997-01-30 DK DK97902295T patent/DK0880523T3/da active
- 1997-01-30 IL IL12383597A patent/IL123835A0/xx active IP Right Grant
- 1997-01-30 EE EE9800124A patent/EE04282B1/xx not_active IP Right Cessation
- 1997-01-30 EA EA199800394A patent/EA000803B1/ru not_active IP Right Cessation
- 1997-02-05 TW TW086101373A patent/TW449599B/zh not_active IP Right Cessation
- 1997-02-06 AR ARP970100473A patent/AR008577A1/es not_active Application Discontinuation
- 1997-02-07 ID IDP970392A patent/ID15905A/id unknown
1998
- 1998-03-25 NO NO19981357A patent/NO310292B1/no not_active IP Right Cessation
- 1998-03-25 BG BG102349A patent/BG102349A/xx unknown
2001
- 2001-09-03 JP JP2001265611A patent/JP2002121194A/ja not_active Withdrawn

Also Published As

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

Legal Events

Date	Code	Title	Description
2013-08-26	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO310292B1 (no)	2001-06-18	Pyrazolpyrimidiner
US20060270659A1 (en)	2006-11-30	Pyrazolopyrimidines as CRF receptor antagonists
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.
NL1026029C2 (nl)	2005-07-05	Cannabinoïdreceptorliganden en toepassingen daarvan.
EP2376490B1 (de)	2013-01-23	Imidazopyridinverbindungen
PL200939B1 (pl)	2009-02-27	Związki [1,5-a]-pirazolo-1,3,5-triazynowe, środek farmaceutyczny i zastosowanie tych związków
EP0863882B1 (de)	2002-02-06	Amino substituierte pyrimidinen und triazinen
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