NO330612B1 - Tetrahydrokinolinderivater, farmasoytisk preparat omfattende slike, slike forbindelser for anvendelse i terapi samt anvendelse av slike for fremstilling av medikament for fruktbarhetsregulering - Google Patents
Tetrahydrokinolinderivater, farmasoytisk preparat omfattende slike, slike forbindelser for anvendelse i terapi samt anvendelse av slike for fremstilling av medikament for fruktbarhetsregulering Download PDFInfo
- Publication number
- NO330612B1 NO330612B1 NO20052727A NO20052727A NO330612B1 NO 330612 B1 NO330612 B1 NO 330612B1 NO 20052727 A NO20052727 A NO 20052727A NO 20052727 A NO20052727 A NO 20052727A NO 330612 B1 NO330612 B1 NO 330612B1
- Authority
- NO
- Norway
- Prior art keywords
- alkoxy
- phenyl
- trimethyl
- compounds
- yield
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 8
- 230000035558 fertility Effects 0.000 title claims description 7
- 230000033228 biological regulation Effects 0.000 title claims description 4
- 229940079593 drug Drugs 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 238000002560 therapeutic procedure Methods 0.000 title claims description 3
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title claims 6
- 150000001875 compounds Chemical class 0.000 title description 279
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 125000003545 alkoxy group Chemical group 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- -1 furylcarbonylamino Chemical group 0.000 claims description 36
- 125000003282 alkyl amino group Chemical group 0.000 claims description 22
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 4
- 238000000034 method Methods 0.000 description 174
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 72
- 239000000460 chlorine Substances 0.000 description 70
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 58
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 49
- 239000000203 mixture Substances 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
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- 239000000243 solution Substances 0.000 description 39
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- 238000004587 chromatography analysis Methods 0.000 description 36
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- 238000002953 preparative HPLC Methods 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
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- 229910001868 water Inorganic materials 0.000 description 24
- 125000004432 carbon atom Chemical group C* 0.000 description 22
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 20
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- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 19
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 229940028334 follicle stimulating hormone Drugs 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 15
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
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- 108020003175 receptors Proteins 0.000 description 15
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- 229960000583 acetic acid Drugs 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
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- 238000000746 purification Methods 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 238000010520 demethylation reaction Methods 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- VCNGNQLPFHVODE-UHFFFAOYSA-N 5-methylthiophene-2-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)S1 VCNGNQLPFHVODE-UHFFFAOYSA-N 0.000 description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 10
- 108010060374 FSH Receptors Proteins 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 150000003530 tetrahydroquinolines Chemical class 0.000 description 9
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 8
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- 238000005917 acylation reaction Methods 0.000 description 8
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- 125000001072 heteroaryl group Chemical group 0.000 description 8
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- 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 8
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- SFTFNJZWZHASAQ-UHFFFAOYSA-N 3,5-dibromobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1 SFTFNJZWZHASAQ-UHFFFAOYSA-N 0.000 description 5
- QZLSBOVWPHXCLT-UHFFFAOYSA-N 5-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)S1 QZLSBOVWPHXCLT-UHFFFAOYSA-N 0.000 description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43504002P | 2002-12-20 | 2002-12-20 | |
EP02102866 | 2002-12-20 | ||
PCT/EP2003/051025 WO2004056780A2 (en) | 2002-12-20 | 2003-12-16 | Tetrahydroquinoline derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20052727D0 NO20052727D0 (no) | 2005-06-07 |
NO20052727L NO20052727L (no) | 2005-07-13 |
NO330612B1 true NO330612B1 (no) | 2011-05-30 |
Family
ID=32683821
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20052727A NO330612B1 (no) | 2002-12-20 | 2005-06-07 | Tetrahydrokinolinderivater, farmasoytisk preparat omfattende slike, slike forbindelser for anvendelse i terapi samt anvendelse av slike for fremstilling av medikament for fruktbarhetsregulering |
Country Status (10)
Country | Link |
---|---|
KR (1) | KR20050084341A (ko) |
CO (1) | CO5590903A2 (ko) |
DE (1) | DE60326390D1 (ko) |
EC (1) | ECSP055871A (ko) |
EG (1) | EG24958A (ko) |
HK (1) | HK1077577A1 (ko) |
HR (1) | HRP20050576A2 (ko) |
IS (1) | IS2647B (ko) |
MX (1) | MXPA05006767A (ko) |
NO (1) | NO330612B1 (ko) |
-
2003
- 2003-12-16 MX MXPA05006767A patent/MXPA05006767A/es active IP Right Grant
- 2003-12-16 DE DE60326390T patent/DE60326390D1/de not_active Expired - Lifetime
- 2003-12-16 KR KR1020057011089A patent/KR20050084341A/ko active IP Right Grant
-
2005
- 2005-05-26 IS IS7871A patent/IS2647B/is unknown
- 2005-06-07 NO NO20052727A patent/NO330612B1/no not_active IP Right Cessation
- 2005-06-18 EG EGNA2005000309 patent/EG24958A/xx active
- 2005-06-20 EC EC2005005871A patent/ECSP055871A/es unknown
- 2005-06-20 HR HR20050576A patent/HRP20050576A2/hr not_active Application Discontinuation
- 2005-07-19 CO CO05071364A patent/CO5590903A2/es not_active Application Discontinuation
- 2005-12-28 HK HK05112055.2A patent/HK1077577A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
KR20050084341A (ko) | 2005-08-26 |
MXPA05006767A (es) | 2005-09-08 |
IS7871A (is) | 2005-05-26 |
IS2647B (is) | 2010-08-15 |
DE60326390D1 (en) | 2009-04-09 |
HRP20050576A2 (en) | 2005-10-31 |
EG24958A (en) | 2011-02-28 |
NO20052727L (no) | 2005-07-13 |
NO20052727D0 (no) | 2005-06-07 |
ECSP055871A (es) | 2005-09-20 |
HK1077577A1 (en) | 2006-02-17 |
CO5590903A2 (es) | 2005-12-30 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |