ZA200201760B - Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as D4 antagnosists. - Google Patents

Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as D4 antagnosists. Download PDF

Info

Publication number: ZA200201760B
Authority: ZA; South Africa
Prior art keywords: compound; thieno; phenoxy; amine; substance
Prior art date: 1999-09-14

Application number

ZA200201760A

Other languages

English (en)

Inventor

George E Lee

John G Jurcak

Timothy A Ayers

Original Assignee

Aventis Pharma 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.)

1999-09-14

Filing date

2002-03-01

Publication date

2003-08-27

2002-03-01 Application filed by Aventis Pharma Inc filed Critical Aventis Pharma Inc

2003-08-27 Publication of ZA200201760B publication Critical patent/ZA200201760B/en

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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 154
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 70
239000000126 substance Substances 0.000 claims description 54
-1 1,2,3,4-tetrahydronaphthyl Chemical group 0.000 claims description 45
238000000034 method Methods 0.000 claims description 41
229960003638 dopamine Drugs 0.000 claims description 35
125000000217 alkyl group Chemical group 0.000 claims description 26
239000003814 drug Substances 0.000 claims description 26
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 23
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 23
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 21
208000011117 substance-related disease Diseases 0.000 claims description 20
238000004519 manufacturing process Methods 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000004076 pyridyl group Chemical group 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
208000018737 Parkinson disease Diseases 0.000 claims description 14
208000028017 Psychotic disease Diseases 0.000 claims description 12
230000000694 effects Effects 0.000 claims description 12
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 12
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 9
125000002757 morpholinyl group Chemical group 0.000 claims description 9
125000003386 piperidinyl group Chemical group 0.000 claims description 9
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
201000009032 substance abuse Diseases 0.000 claims description 9
125000001544 thienyl group Chemical group 0.000 claims description 9
208000027691 Conduct disease Diseases 0.000 claims description 8
206010043118 Tardive Dyskinesia Diseases 0.000 claims description 8
231100000736 substance abuse Toxicity 0.000 claims description 8
208000000323 Tourette Syndrome Diseases 0.000 claims description 7
208000016620 Tourette disease Diseases 0.000 claims description 7
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 7
125000003725 azepanyl group Chemical group 0.000 claims description 7
125000004193 piperazinyl group Chemical group 0.000 claims description 7
201000006152 substance dependence Diseases 0.000 claims description 7
125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 6
208000027448 Attention Deficit and Disruptive Behavior disease Diseases 0.000 claims description 6
201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 6
208000027089 Parkinsonian disease Diseases 0.000 claims description 6
206010034010 Parkinsonism Diseases 0.000 claims description 6
125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 6
125000001624 naphthyl group Chemical group 0.000 claims description 6
208000024196 oppositional defiant disease Diseases 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
230000003042 antagnostic effect Effects 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims 15
WCZJWEXDYDOXMQ-UHFFFAOYSA-N n-[(3-fluorophenyl)methyl]-2-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)ethanamine Chemical compound FC1=CC=CC(CNCCOC=2C=C(C=CC=2)C=2C=3SC=CC=3ON=2)=C1 WCZJWEXDYDOXMQ-UHFFFAOYSA-N 0.000 claims 14
239000003153 chemical reaction reagent Substances 0.000 claims 6
230000008878 coupling Effects 0.000 claims 3
238000010168 coupling process Methods 0.000 claims 3
238000005859 coupling reaction Methods 0.000 claims 3
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 2
FXDBDRGPUVHZTJ-UHFFFAOYSA-N 2-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)-n-(thiophen-3-ylmethyl)ethanamine Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCNCC=1C=CSC=1 FXDBDRGPUVHZTJ-UHFFFAOYSA-N 0.000 claims 1
OEGGHDNBSNBJSC-UHFFFAOYSA-N 2-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)-n-[[2-(trifluoromethyl)phenyl]methyl]ethanamine Chemical compound FC(F)(F)C1=CC=CC=C1CNCCOC1=CC=CC(C=2C=3SC=CC=3ON=2)=C1 OEGGHDNBSNBJSC-UHFFFAOYSA-N 0.000 claims 1
AXWKUSGIBQSCJM-UHFFFAOYSA-N 2-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)-n-[[4-(trifluoromethyl)phenyl]methyl]ethanamine Chemical compound C1=CC(C(F)(F)F)=CC=C1CNCCOC1=CC=CC(C=2C=3SC=CC=3ON=2)=C1 AXWKUSGIBQSCJM-UHFFFAOYSA-N 0.000 claims 1
WTTQMXMDSSTLAK-UHFFFAOYSA-N 3-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)-n-[[4-(trifluoromethyl)phenyl]methyl]propan-1-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CNCCCOC1=CC=CC(C=2C=3SC=CC=3ON=2)=C1 WTTQMXMDSSTLAK-UHFFFAOYSA-N 0.000 claims 1
HTJBIZSOLCGIHU-UHFFFAOYSA-N 3-[3-(2-piperidin-1-ylethoxy)phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCN1CCCCC1 HTJBIZSOLCGIHU-UHFFFAOYSA-N 0.000 claims 1
WOSQLRBINIONCR-UHFFFAOYSA-N 3-[3-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCN1CCCC1 WOSQLRBINIONCR-UHFFFAOYSA-N 0.000 claims 1
YCYNJGDVCCVPLU-UHFFFAOYSA-N 3-[3-[2-(4-phenylpiperazin-1-yl)ethoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCN(CC1)CCN1C1=CC=CC=C1 YCYNJGDVCCVPLU-UHFFFAOYSA-N 0.000 claims 1
JKFNAVCQTQWGGV-UHFFFAOYSA-N 3-[3-[2-(azocan-1-yl)ethoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCN1CCCCCCC1 JKFNAVCQTQWGGV-UHFFFAOYSA-N 0.000 claims 1
QQFGMACPARAORV-UHFFFAOYSA-N 3-[3-[3-(3,4-dihydro-1h-isoquinolin-2-yl)propoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C1CC2=CC=CC=C2CN1CCCOC1=CC=CC(C=2C=3SC=CC=3ON=2)=C1 QQFGMACPARAORV-UHFFFAOYSA-N 0.000 claims 1
ZTDXYBZRQGLMPI-UHFFFAOYSA-N 3-[3-[3-(4-phenylpiperazin-1-yl)propoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCCN(CC1)CCN1C1=CC=CC=C1 ZTDXYBZRQGLMPI-UHFFFAOYSA-N 0.000 claims 1
QZTPDKPNAHXFLH-UHFFFAOYSA-N 3-[3-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCCN(CC1)CCN1C1=NC=CC=N1 QZTPDKPNAHXFLH-UHFFFAOYSA-N 0.000 claims 1
RIOZKBNPMPJRGT-UHFFFAOYSA-N 3-[3-[3-[4-(2-fluorophenyl)piperazin-1-yl]propoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound FC1=CC=CC=C1N1CCN(CCCOC=2C=C(C=CC=2)C=2C=3SC=CC=3ON=2)CC1 RIOZKBNPMPJRGT-UHFFFAOYSA-N 0.000 claims 1
FNTHHCINSHLECV-UHFFFAOYSA-N 3-[3-[3-[4-(4-fluorophenyl)piperazin-1-yl]propoxy]phenyl]thieno[2,3-d][1,2]oxazole Chemical compound C1=CC(F)=CC=C1N1CCN(CCCOC=2C=C(C=CC=2)C=2C=3SC=CC=3ON=2)CC1 FNTHHCINSHLECV-UHFFFAOYSA-N 0.000 claims 1
AKXYBAMUEBLIDH-UHFFFAOYSA-N 4-[2-[3-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)propylamino]ethyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNCCCOC1=CC=CC(C=2C=3SC=CC=3ON=2)=C1 AKXYBAMUEBLIDH-UHFFFAOYSA-N 0.000 claims 1
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YNMQQYFYJJVPTK-UHFFFAOYSA-N n-benzyl-2-(3-thieno[2,3-d][1,2]oxazol-3-ylphenoxy)ethanamine Chemical compound C=1C=CC(C=2C=3SC=CC=3ON=2)=CC=1OCCNCC1=CC=CC=C1 YNMQQYFYJJVPTK-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Psychology (AREA)
Psychiatry (AREA)
Addiction (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

ZA200201760A 1999-09-14 2002-03-01 Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as D4 antagnosists. ZA200201760B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US39615699A	1999-09-14	1999-09-14

Publications (1)

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ZA200201760B true ZA200201760B (en)	2003-08-27

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ZA200201760A ZA200201760B (en)	1999-09-14	2002-03-01	Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as D4 antagnosists.

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EP (1)	EP1216249B1 (de)
JP (1)	JP4717306B2 (de)
KR (1)	KR20020027644A (de)
AR (1)	AR032135A1 (de)
AT (1)	ATE254620T1 (de)
AU (1)	AU7577200A (de)
BR (1)	BR0014513A (de)
CA (1)	CA2383327C (de)
CZ (1)	CZ2002896A3 (de)
DE (1)	DE60006698T2 (de)
DK (1)	DK1216249T3 (de)
EA (1)	EA004177B1 (de)
EE (1)	EE200200133A (de)
ES (1)	ES2206305T3 (de)
HU (1)	HUP0202712A3 (de)
IL (1)	IL148522A0 (de)
MX (1)	MXPA02002690A (de)
NO (1)	NO20021249L (de)
PL (1)	PL354481A1 (de)
PT (1)	PT1216249E (de)
SK (1)	SK3502002A3 (de)
WO (1)	WO2001019832A2 (de)
ZA (1)	ZA200201760B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0207449D0 (en) *	2002-03-28	2002-05-08	Glaxo Group Ltd	Novel compounds
WO2018166855A1 (en)	2017-03-16	2018-09-20	Basf Se	Heterobicyclic substituted dihydroisoxazoles

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4728651A (en) *	1985-10-24	1988-03-01	Hoechst-Roussel Pharmaceuticals Inc.	Antihypertensive thieno-isoxazoles and -pyrazoles
US6187774B1 (en) *	1996-03-04	2001-02-13	Yoshitomi Pharmaceutical Industries, Ltd.	Fused heterocyclic compounds and pharmaceutical applications thereof
HUP9603001A3 (en) *	1996-10-30	1999-07-28	Richter Gedeon Vegyeszet	Heterocycle compounds comprising nitrogen, process for producing them and pharmaceutical compositions containing the same
JP4627882B2 (ja) *	1998-02-09	2011-02-09	デユフアー・インターナシヨナル・リサーチ・ベー・ブイ	Ｄ４−アンタゴニスト活性を有するベンズイソキサゾール誘導体

2000
- 2000-09-13 HU HU0202712A patent/HUP0202712A3/hu unknown
- 2000-09-13 MX MXPA02002690A patent/MXPA02002690A/es active IP Right Grant
- 2000-09-13 JP JP2001523409A patent/JP4717306B2/ja not_active Expired - Fee Related
- 2000-09-13 SK SK350-2002A patent/SK3502002A3/sk unknown
- 2000-09-13 AR ARP000104794A patent/AR032135A1/es not_active Application Discontinuation
- 2000-09-13 IL IL14852200A patent/IL148522A0/xx unknown
- 2000-09-13 EA EA200200357A patent/EA004177B1/ru not_active IP Right Cessation
- 2000-09-13 ES ES00964967T patent/ES2206305T3/es not_active Expired - Lifetime
- 2000-09-13 PT PT00964967T patent/PT1216249E/pt unknown
- 2000-09-13 KR KR1020027003354A patent/KR20020027644A/ko not_active Withdrawn
- 2000-09-13 CZ CZ2002896A patent/CZ2002896A3/cs unknown
- 2000-09-13 EE EEP200200133A patent/EE200200133A/xx unknown
- 2000-09-13 AU AU75772/00A patent/AU7577200A/en not_active Abandoned
- 2000-09-13 CA CA002383327A patent/CA2383327C/en not_active Expired - Fee Related
- 2000-09-13 PL PL00354481A patent/PL354481A1/xx unknown
- 2000-09-13 AT AT00964967T patent/ATE254620T1/de not_active IP Right Cessation
- 2000-09-13 DK DK00964967T patent/DK1216249T3/da active
- 2000-09-13 WO PCT/US2000/024949 patent/WO2001019832A2/en not_active Ceased
- 2000-09-13 BR BR0014513-0A patent/BR0014513A/pt not_active IP Right Cessation
- 2000-09-13 EP EP00964967A patent/EP1216249B1/de not_active Expired - Lifetime
- 2000-09-13 DE DE60006698T patent/DE60006698T2/de not_active Expired - Lifetime
2002
- 2002-03-01 ZA ZA200201760A patent/ZA200201760B/en unknown
- 2002-03-13 NO NO20021249A patent/NO20021249L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
IL148522A0 (en)	2002-09-12
CA2383327A1 (en)	2001-03-22
CZ2002896A3 (cs)	2002-08-14
AU7577200A (en)	2001-04-17
JP2003509431A (ja)	2003-03-11
EA200200357A1 (ru)	2002-10-31
EP1216249A2 (de)	2002-06-26
HUP0202712A3 (en)	2004-12-28
EE200200133A (et)	2003-04-15
SK3502002A3 (en)	2002-09-10
EA004177B1 (ru)	2004-02-26
DE60006698T2 (de)	2004-09-23
NO20021249D0 (no)	2002-03-13
MXPA02002690A (es)	2004-09-10
JP4717306B2 (ja)	2011-07-06
DE60006698D1 (de)	2003-12-24
AR032135A1 (es)	2003-10-29
ATE254620T1 (de)	2003-12-15
WO2001019832A3 (en)	2001-10-04
CA2383327C (en)	2009-11-03
BR0014513A (pt)	2002-07-02
NO20021249L (no)	2002-05-10
ES2206305T3 (es)	2004-05-16
EP1216249B1 (de)	2003-11-19
PT1216249E (pt)	2004-04-30
KR20020027644A (ko)	2002-04-13
DK1216249T3 (da)	2004-03-15
HUP0202712A2 (hu)	2002-12-28
PL354481A1 (en)	2004-01-26
WO2001019832A2 (en)	2001-03-22

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DE60004543T2 (de)	2004-06-17	Benzisoxazolyl-, pyridoisoxazolyl- und benzthienyl-phenoxy derivate als d4 antagonisten
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