AU2001276903A1 - Imidazo(1,2-a)pyrazines for the treatment of neurological disorders - Google Patents

Imidazo(1,2-a)pyrazines for the treatment of neurological disorders

Info

Publication number: AU2001276903A1
Authority: AU; Australia
Prior art keywords: alkyl; compound; cycloalkyl; crf; compounds
Prior art date: 2000-07-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

AU2001276903A

Other languages

English (en)

Inventor

Rajagopal Bakthavatachalam

Paul J. Gilligan

Richard G. Wilde

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

Bristol Myers Squibb Pharma Co

Original Assignee

DuPont Merck Pharmaceutical Co

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.)

2000-07-14

Filing date

2001-07-13

Publication date

2002-01-30

2001-07-13 Application filed by DuPont Merck Pharmaceutical Co filed Critical DuPont Merck Pharmaceutical Co

2002-01-30 Publication of AU2001276903A1 publication Critical patent/AU2001276903A1/en

Status Abandoned legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims description 119
102100021752 Corticoliberin Human genes 0.000 claims description 45
125000000217 alkyl group Chemical group 0.000 claims description 28
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 23
-1 cyano, dimethylamino Chemical group 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 18
150000002367 halogens Chemical class 0.000 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000001072 heteroaryl group Chemical group 0.000 claims description 14
238000000034 method Methods 0.000 claims description 13
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 9
208000019901 Anxiety disease Diseases 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
230000036506 anxiety Effects 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
125000001188 haloalkyl group Chemical group 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
230000002018 overexpression Effects 0.000 claims description 4
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 4
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 46
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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235000019439 ethyl acetate Nutrition 0.000 description 25
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239000011541 reaction mixture Substances 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
239000007787 solid Substances 0.000 description 19
150000003839 salts Chemical class 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
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125000001424 substituent group Chemical group 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
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229910052757 nitrogen Inorganic materials 0.000 description 12
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238000003818 flash chromatography Methods 0.000 description 10
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
230000003542 behavioural effect Effects 0.000 description 9
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238000006243 chemical reaction Methods 0.000 description 8
239000000243 solution Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
MBVAHHOKMIRXLP-UHFFFAOYSA-N imidazo[1,2-a]pyrazine Chemical compound C1=CN=CC2=NC=CN21 MBVAHHOKMIRXLP-UHFFFAOYSA-N 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
239000002904 solvent Substances 0.000 description 7
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 6
GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical class CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 6
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QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 6
108090000765 processed proteins & peptides Proteins 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
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238000012360 testing method Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000002249 anxiolytic agent Substances 0.000 description 5
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150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
239000002585 base Substances 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
239000002769 corticotropin releasing factor antagonist Substances 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
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239000002858 neurotransmitter agent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
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241001465754 Metazoa Species 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
108010069820 Pro-Opiomelanocortin Proteins 0.000 description 4
239000000683 Pro-Opiomelanocortin Substances 0.000 description 4
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125000004432 carbon atom Chemical group C* 0.000 description 4
210000001175 cerebrospinal fluid Anatomy 0.000 description 4
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 4
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150000004292 cyclic ethers Chemical class 0.000 description 4
150000001983 dialkylethers Chemical class 0.000 description 4
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230000004044 response Effects 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
AEVSSZHXGJAPIE-UHFFFAOYSA-N 3-chloropyrazin-2-amine Chemical compound NC1=NC=CN=C1Cl AEVSSZHXGJAPIE-UHFFFAOYSA-N 0.000 description 3
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- 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
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Child & Adolescent Psychology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

AU2001276903A 2000-07-14 2001-07-13 Imidazo(1,2-a)pyrazines for the treatment of neurological disorders Abandoned AU2001276903A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US21833900P	2000-07-14	2000-07-14
US60218339		2000-07-14
PCT/US2001/022076 WO2002006286A2 (fr)	2000-07-14	2001-07-13	Imidazo[1,2-a]pyrazines destinees au traitement d'affections neurologiques

Publications (1)

Publication Number	Publication Date
AU2001276903A1 true AU2001276903A1 (en)	2002-01-30

Family

ID=22814709

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU2001276903A Abandoned AU2001276903A1 (en)	2000-07-14	2001-07-13	Imidazo(1,2-a)pyrazines for the treatment of neurological disorders

Country Status (7)

Country	Link
US (2)	US6589952B2 (fr)
EP (1)	EP1301511A2 (fr)
JP (1)	JP2004532792A (fr)
AU (1)	AU2001276903A1 (fr)
CA (1)	CA2419626A1 (fr)
HU (1)	HUP0301801A2 (fr)
WO (1)	WO2002006286A2 (fr)

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2001
- 2001-07-13 EP EP01954675A patent/EP1301511A2/fr not_active Withdrawn
- 2001-07-13 CA CA002419626A patent/CA2419626A1/fr not_active Abandoned
- 2001-07-13 WO PCT/US2001/022076 patent/WO2002006286A2/fr not_active Application Discontinuation
- 2001-07-13 US US09/905,097 patent/US6589952B2/en not_active Expired - Lifetime
- 2001-07-13 AU AU2001276903A patent/AU2001276903A1/en not_active Abandoned
- 2001-07-13 JP JP2002512188A patent/JP2004532792A/ja active Pending
- 2001-07-13 HU HU0301801A patent/HUP0301801A2/hu unknown
2003
- 2003-05-01 US US10/427,234 patent/US20030220342A1/en not_active Abandoned

Also Published As

Publication number	Publication date
US20030220342A1 (en)	2003-11-27
HUP0301801A2 (hu)	2003-09-29
WO2002006286A2 (fr)	2002-01-24
CA2419626A1 (fr)	2002-01-24
WO2002006286A3 (fr)	2002-06-13
JP2004532792A (ja)	2004-10-28
EP1301511A2 (fr)	2003-04-16
US20020049208A1 (en)	2002-04-25
US6589952B2 (en)	2003-07-08

Publication	Publication Date	Title
AU2001276903A1 (en)	2002-01-30	Imidazo(1,2-a)pyrazines for the treatment of neurological disorders
JP4228332B2 (ja)	2009-02-25	アゾロトリアジン類およびアゾロピリミジン類
US7067658B2 (en)	2006-06-27	Pyridino and pyrimidino pyrazinones
KR100548853B1 (ko)	2006-02-02	아졸로 트리아진 및 피리미딘
US6271380B1 (en)	2001-08-07	1H-imidazo[4,5-d]pyridazin-7-ones, 3H-imidazo-[4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (CRF) receptor ligands
US6521636B1 (en)	2003-02-18	Imidazo-pyridines as corticotropin releasing factor antagonists
SK179899A3 (en)	2001-12-03	Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders
US7026317B2 (en)	2006-04-11	Pyrazolotriazines as CRF antagonists
US20030229091A1 (en)	2003-12-11	Heteroaromatic substituted cyclopropane as corticotropin releasing hormone ligands
US20220402927A1 (en)	2022-12-22	Tricyclic compounds, compositions and medicinal applications thereof
JP4704521B2 (ja)	2011-06-15	アゾロトリアジン類およびアゾロピリミジン類
US7045529B2 (en)	2006-05-16	Imidazopyrimidinyl and imidazopyri dinyl derivatives
US7098217B2 (en)	2006-08-29	3,7-dihydro-purine-2,6-dione derivatives as CRF receptor ligands
US20020022619A1 (en)	2002-02-21	Tricyclic fused pyridine and pyrimidine derivatives as CRF antagonists
US20030149059A1 (en)	2003-08-07	Tetrahydropurinones and derivatives thereof as corticotropin releasing factor receptor ligands