SK4782001A3 - Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents) - Google Patents

Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents) Download PDF

Info

Publication number: SK4782001A3
Authority: SK; Slovakia
Prior art keywords: trans; ethyl; tetrahydro; benzazepine; cyclohexyl
Prior art date: 1998-10-08

Application number

SK478-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Stewart Hadley

Christopher Norbert Johnson

Gregor James Macdonald

Geoffrey Stemp

Antonio Kuok Keong Vong

Original Assignee

Smithkline Beecham Plc

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.)

1998-10-08

Filing date

1999-10-06

Publication date

2001-11-06

1998-10-08 Priority claimed from GBGB9821976.9A external-priority patent/GB9821976D0/en

1998-11-06 Priority claimed from GBGB9824340.5A external-priority patent/GB9824340D0/en

1999-05-07 Priority claimed from GBGB9910711.2A external-priority patent/GB9910711D0/en

1999-07-30 Priority claimed from GBGB9918032.5A external-priority patent/GB9918032D0/en

1999-10-06 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

2001-11-06 Publication of SK4782001A3 publication Critical patent/SK4782001A3/sk

Links

MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical class N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 title claims description 28
239000000164 antipsychotic agent Substances 0.000 title abstract description 7
102000004073 Dopamine D3 Receptors Human genes 0.000 title description 3
108090000525 Dopamine D3 Receptors Proteins 0.000 title description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 324
150000001875 compounds Chemical class 0.000 claims abstract description 196
150000003839 salts Chemical class 0.000 claims abstract description 51
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
102000005962 receptors Human genes 0.000 claims abstract description 21
108020003175 receptors Proteins 0.000 claims abstract description 21
239000001257 hydrogen Substances 0.000 claims abstract description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
125000001424 substituent group Chemical group 0.000 claims abstract description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
238000011282 treatment Methods 0.000 claims abstract description 14
229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 12
108050004812 Dopamine receptor Proteins 0.000 claims abstract description 11
102000015554 Dopamine receptor Human genes 0.000 claims abstract description 11
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
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 287
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 287
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 159
-1 2-indolyl Chemical group 0.000 claims description 153
125000004093 cyano group Chemical group *C#N 0.000 claims description 75
125000005518 carboxamido group Chemical group 0.000 claims description 67
MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 claims description 53
229910052786 argon Inorganic materials 0.000 claims description 31
238000000034 method Methods 0.000 claims description 27
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 21
239000008194 pharmaceutical composition Substances 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 12
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
150000003857 carboxamides Chemical group 0.000 claims description 8
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 8
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208000028017 Psychotic disease Diseases 0.000 claims description 7
229910005965 SO 2 Inorganic materials 0.000 claims description 7
125000003435 aroyl group Chemical group 0.000 claims description 7
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238000007796 conventional method Methods 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 6
SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
201000000980 schizophrenia Diseases 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
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229960003638 dopamine Drugs 0.000 claims description 5
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229910052799 carbon Inorganic materials 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
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239000003054 catalyst Substances 0.000 claims description 3
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125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
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UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 2
229940126062 Compound A Drugs 0.000 claims description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 2
IVDZZBGWCCSIRG-UHFFFAOYSA-N N1C(=CC2=CC=CC=C12)CC(=O)NC1CCC(CC1)C(C)C1NCCC2=C(C1)C=CC=C2 Chemical compound N1C(=CC2=CC=CC=C12)CC(=O)NC1CCC(CC1)C(C)C1NCCC2=C(C1)C=CC=C2 IVDZZBGWCCSIRG-UHFFFAOYSA-N 0.000 claims description 2
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
239000002168 alkylating agent Substances 0.000 claims description 2
125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
150000003976 azacycloalkanes Chemical group 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
239000000543 intermediate Substances 0.000 claims description 2
150000002736 metal compounds Chemical class 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims description 2
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239000000126 substance Substances 0.000 claims description 2
208000011117 substance-related disease Diseases 0.000 claims description 2
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims 1
GPPCMFUYKIHTLD-UHFFFAOYSA-N S1C(=CC2=C1C=CC=C2)CC(=O)NC2CCC(CC2)C(C)C2NCCC1=C(C2)C=CC=C1 Chemical compound S1C(=CC2=C1C=CC=C2)CC(=O)NC2CCC(CC2)C(C)C2NCCC1=C(C2)C=CC=C1 GPPCMFUYKIHTLD-UHFFFAOYSA-N 0.000 claims 1
125000003282 alkyl amino group Chemical group 0.000 claims 1
125000005422 alkyl sulfonamido group Chemical group 0.000 claims 1
150000001638 boron Chemical class 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
125000004663 dialkyl amino group Chemical group 0.000 claims 1
239000003210 dopamine receptor blocking agent Substances 0.000 claims 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
201000006152 substance dependence Diseases 0.000 claims 1
230000009286 beneficial effect Effects 0.000 abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
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229920006395 saturated elastomer Polymers 0.000 description 36
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238000006243 chemical reaction Methods 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
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ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 12
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
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Classifications

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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07—ORGANIC CHEMISTRY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- C07D471/04—Ortho-condensed systems

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SK478-2001A 1998-10-08 1999-10-06 Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents) SK4782001A3 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GBGB9821976.9A GB9821976D0 (en)	1998-10-08	1998-10-08	Compounds
GBGB9824340.5A GB9824340D0 (en)	1998-11-06	1998-11-06	Compounds
GBGB9910711.2A GB9910711D0 (en)	1999-05-07	1999-05-07	Compounds
GBGB9918032.5A GB9918032D0 (en)	1999-07-30	1999-07-30	Compounds
PCT/EP1999/007763 WO2000021951A1 (fr)	1998-10-08	1999-10-06	Derives de tetrahydrobenzozepine utiles comme modulateurs des recepteurs de la la dopamine d3

Publications (1)

Publication Number	Publication Date
SK4782001A3 true SK4782001A3 (en)	2001-11-06

Family

ID=27451837

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK478-2001A SK4782001A3 (en)	1998-10-08	1999-10-06	Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)

Country Status (30)

Country	Link
US (1)	US6605607B1 (fr)
EP (1)	EP1119563B1 (fr)
JP (1)	JP2002527433A (fr)
KR (1)	KR20010085898A (fr)
CN (1)	CN1329609A (fr)
AP (1)	AP2001002114A0 (fr)
AR (1)	AR023681A1 (fr)
AT (1)	ATE316969T1 (fr)
AU (1)	AU761018B2 (fr)
BG (1)	BG105467A (fr)
BR (1)	BR9914370A (fr)
CA (1)	CA2346689A1 (fr)
CO (1)	CO5140073A1 (fr)
CZ (1)	CZ20011270A3 (fr)
DE (1)	DE69929704T2 (fr)
EA (1)	EA200100428A1 (fr)
ES (1)	ES2255311T3 (fr)
HK (1)	HK1038745A1 (fr)
HU (1)	HUP0104280A3 (fr)
ID (1)	ID28385A (fr)
IL (1)	IL142388A0 (fr)
MA (1)	MA26696A1 (fr)
NO (1)	NO20011745L (fr)
NZ (1)	NZ511018A (fr)
OA (1)	OA11663A (fr)
PE (1)	PE20001088A1 (fr)
PL (1)	PL347237A1 (fr)
SK (1)	SK4782001A3 (fr)
TR (1)	TR200101025T2 (fr)
WO (1)	WO2000021951A1 (fr)

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1999
- 1999-10-06 WO PCT/EP1999/007763 patent/WO2000021951A1/fr not_active Ceased
- 1999-10-06 CZ CZ20011270A patent/CZ20011270A3/cs unknown
- 1999-10-06 AP APAP/P/2001/002114A patent/AP2001002114A0/en unknown
- 1999-10-06 CO CO99063348A patent/CO5140073A1/es unknown
- 1999-10-06 ES ES99953833T patent/ES2255311T3/es not_active Expired - Lifetime
- 1999-10-06 MA MA25809A patent/MA26696A1/fr unknown
- 1999-10-06 AT AT99953833T patent/ATE316969T1/de not_active IP Right Cessation
- 1999-10-06 EP EP99953833A patent/EP1119563B1/fr not_active Expired - Lifetime
- 1999-10-06 SK SK478-2001A patent/SK4782001A3/sk unknown
- 1999-10-06 IL IL14238899A patent/IL142388A0/xx unknown
- 1999-10-06 TR TR2001/01025T patent/TR200101025T2/xx unknown
- 1999-10-06 ID IDW20010785A patent/ID28385A/id unknown
- 1999-10-06 CN CN99814062A patent/CN1329609A/zh active Pending
- 1999-10-06 HU HU0104280A patent/HUP0104280A3/hu unknown
- 1999-10-06 HK HK02100150.4A patent/HK1038745A1/zh unknown
- 1999-10-06 PE PE1999001015A patent/PE20001088A1/es not_active Application Discontinuation
- 1999-10-06 AU AU10381/00A patent/AU761018B2/en not_active Ceased
- 1999-10-06 AR ARP990105055A patent/AR023681A1/es not_active Application Discontinuation
- 1999-10-06 BR BR9914370-4A patent/BR9914370A/pt not_active IP Right Cessation
- 1999-10-06 NZ NZ511018A patent/NZ511018A/en unknown
- 1999-10-06 CA CA002346689A patent/CA2346689A1/fr not_active Abandoned
- 1999-10-06 OA OA1200100090A patent/OA11663A/en unknown
- 1999-10-06 JP JP2000575857A patent/JP2002527433A/ja not_active Withdrawn
- 1999-10-06 EA EA200100428A patent/EA200100428A1/ru unknown
- 1999-10-06 KR KR1020017004442A patent/KR20010085898A/ko not_active Withdrawn
- 1999-10-06 US US09/806,902 patent/US6605607B1/en not_active Expired - Fee Related
- 1999-10-06 DE DE69929704T patent/DE69929704T2/de not_active Expired - Fee Related
- 1999-10-06 PL PL99347237A patent/PL347237A1/xx not_active Application Discontinuation
2001
- 2001-04-06 NO NO20011745A patent/NO20011745L/no not_active Application Discontinuation
- 2001-04-24 BG BG105467A patent/BG105467A/xx unknown

Also Published As

Publication number	Publication date
NO20011745L (no)	2001-06-06
IL142388A0 (en)	2002-03-10
US6605607B1 (en)	2003-08-12
AU1038100A (en)	2000-05-01
MA26696A1 (fr)	2004-12-20
AU761018B2 (en)	2003-05-29
DE69929704D1 (de)	2006-04-13
EA200100428A1 (ru)	2001-10-22
WO2000021951A1 (fr)	2000-04-20
HK1038745A1 (zh)	2002-03-28
NO20011745D0 (no)	2001-04-06
PL347237A1 (en)	2002-03-25
CO5140073A1 (es)	2002-03-22
KR20010085898A (ko)	2001-09-07
TR200101025T2 (tr)	2001-09-21
CZ20011270A3 (cs)	2001-09-12
BG105467A (en)	2001-11-30
CN1329609A (zh)	2002-01-02
OA11663A (en)	2004-12-08
JP2002527433A (ja)	2002-08-27
BR9914370A (pt)	2001-11-27
AP2001002114A0 (en)	2001-06-30
ATE316969T1 (de)	2006-02-15
HUP0104280A3 (en)	2002-07-29
AR023681A1 (es)	2002-09-04
DE69929704T2 (de)	2006-07-20
ES2255311T3 (es)	2006-06-16
HUP0104280A2 (hu)	2002-03-28
EP1119563B1 (fr)	2006-02-01
EP1119563A1 (fr)	2001-08-01
NZ511018A (en)	2003-09-26
CA2346689A1 (fr)	2000-04-20
ID28385A (id)	2001-05-17
PE20001088A1 (es)	2000-12-02

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