OA11011A - Quinoline-4-carboxamide derivatives their preparation and their use as neurokin 3 (nk-3)-and neurokin 2 (nk-2)receptor antagonists - Google Patents

Quinoline-4-carboxamide derivatives their preparation and their use as neurokin 3 (nk-3)-and neurokin 2 (nk-2)receptor antagonists Download PDF

Info

Publication number: OA11011A
Authority: OA; OAPI
Prior art keywords: group; alkyl; compound; formula; mmol
Prior art date: 1995-11-24

Application number

OA9800062A

Other languages

English (en)

Inventor

Giuseppe Amaldo Maria

Mario Grugni

Luca Francesco Raveglia

Carlo Farina

Original Assignee

Smithkline Beecham Spa

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.)

1995-11-24

Filing date

1998-05-22

Publication date

2003-03-06

1995-11-24 Priority claimed from ITMI952462 external-priority patent/IT1276171B1/it

1996-08-02 Priority claimed from IT96MI001688 external-priority patent/IT1307330B1/it

1998-05-22 Application filed by Smithkline Beecham Spa filed Critical Smithkline Beecham Spa

2003-03-06 Publication of OA11011A publication Critical patent/OA11011A/en

Links

LEWDKQKVAFOMPI-UHFFFAOYSA-N quinoline-4-carboxamide Chemical class C1=CC=C2C(C(=O)N)=CC=NC2=C1 LEWDKQKVAFOMPI-UHFFFAOYSA-N 0.000 title description 4
239000002464 receptor antagonist Substances 0.000 title description 4
229940044551 receptor antagonist Drugs 0.000 title description 4
238000002360 preparation method Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 232
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
-1 cyano, carboxy Chemical group 0.000 claims abstract description 41
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
125000003118 aryl group Chemical group 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 23
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 19
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 18
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
229910052736 halogen Inorganic materials 0.000 claims abstract description 17
150000002367 halogens Chemical class 0.000 claims abstract description 17
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 6
229910052799 carbon Inorganic materials 0.000 claims abstract description 6
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
125000000278 alkyl amino alkyl group Chemical group 0.000 claims abstract description 5
125000003277 amino group Chemical group 0.000 claims abstract description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 5
125000005544 phthalimido group Chemical group 0.000 claims abstract description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
125000004945 acylaminoalkyl group Chemical group 0.000 claims abstract description 3
125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims abstract description 3
125000005518 carboxamido group Chemical group 0.000 claims abstract description 3
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
230000008569 process Effects 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 5
125000004043 oxo group Chemical group O=* 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000002837 carbocyclic group Chemical group 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 2
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 10
238000011321 prophylaxis Methods 0.000 claims 2
125000004093 cyano group Chemical group *C#N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 20
125000001424 substituent group Chemical group 0.000 abstract description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 2
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 2
125000006727 (C1-C6) alkenyl group Chemical group 0.000 abstract 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 1
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 abstract 1
239000012453 solvate Substances 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 174
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
239000000203 mixture Substances 0.000 description 96
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
235000019439 ethyl acetate Nutrition 0.000 description 71
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 57
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
239000008279 sol Substances 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 47
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 45
239000003480 eluent Substances 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
239000011541 reaction mixture Substances 0.000 description 42
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 41
235000011114 ammonium hydroxide Nutrition 0.000 description 41
238000005481 NMR spectroscopy Methods 0.000 description 37
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
239000000741 silica gel Substances 0.000 description 33
229910002027 silica gel Inorganic materials 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
238000003818 flash chromatography Methods 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
239000011780 sodium chloride Substances 0.000 description 28
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000002904 solvent Substances 0.000 description 26
239000000243 solution Substances 0.000 description 25
239000012043 crude product Substances 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 18
239000007787 solid Substances 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
238000000921 elemental analysis Methods 0.000 description 16
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 16
235000015165 citric acid Nutrition 0.000 description 15
229960004106 citric acid Drugs 0.000 description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
239000000460 chlorine Substances 0.000 description 12
239000002253 acid Substances 0.000 description 11
238000001816 cooling Methods 0.000 description 11
208000035475 disorder Diseases 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
239000003208 petroleum Substances 0.000 description 11
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
238000010992 reflux Methods 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 9
230000000694 effects Effects 0.000 description 9
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
125000006413 ring segment Chemical group 0.000 description 9
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 8
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
235000015320 potassium carbonate Nutrition 0.000 description 8
239000007832 Na2SO4 Substances 0.000 description 7
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
239000000499 gel Substances 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 6
ZSVACLAZDFXWQG-UHFFFAOYSA-N 3-methyl-2-phenylquinoline-4-carboxylic acid Chemical compound N1=C2C=CC=CC2=C(C(O)=O)C(C)=C1C1=CC=CC=C1 ZSVACLAZDFXWQG-UHFFFAOYSA-N 0.000 description 6
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101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 description 6
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230000003197 catalytic effect Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
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XAPRFLSJBSXESP-UHFFFAOYSA-N oxycinchophen Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=C(O)C=1C1=CC=CC=C1 XAPRFLSJBSXESP-UHFFFAOYSA-N 0.000 description 6
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
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MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 4
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PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- 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
- 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
- A61P27/00—Drugs for disorders of the senses
- 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
- 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
- C07D215/52—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4 with aryl radicals attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Immunology (AREA)
Neurosurgery (AREA)
Pulmonology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

OA9800062A 1995-11-24 1998-05-22 Quinoline-4-carboxamide derivatives their preparation and their use as neurokin 3 (nk-3)-and neurokin 2 (nk-2)receptor antagonists OA11011A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ITMI952462 IT1276171B1 (it)	1995-11-24	1995-11-24	Derivati chinolinici
IT96MI001688 IT1307330B1 (it)	1996-08-02	1996-08-02	Derivati chinolinici

Publications (1)

Publication Number	Publication Date
OA11011A true OA11011A (en)	2003-03-06

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ID=26331327

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9800062A OA11011A (en)	1995-11-24	1998-05-22	Quinoline-4-carboxamide derivatives their preparation and their use as neurokin 3 (nk-3)-and neurokin 2 (nk-2)receptor antagonists

Country Status (26)

Country	Link
US (1)	US20020068827A1 (fr)
EP (1)	EP1019377A1 (fr)
JP (1)	JP2000513325A (fr)
KR (1)	KR19990071598A (fr)
CN (1)	CN1207729A (fr)
AP (1)	AP9801238A0 (fr)
AR (1)	AR004735A1 (fr)
AU (1)	AU1031897A (fr)
BG (1)	BG102557A (fr)
BR (1)	BR9611757A (fr)
CA (1)	CA2238328A1 (fr)
CZ (1)	CZ158098A3 (fr)
DZ (1)	DZ2128A1 (fr)
EA (1)	EA001771B1 (fr)
HU (1)	HUP9901016A3 (fr)
IL (1)	IL124418A0 (fr)
MA (1)	MA24011A1 (fr)
MX (1)	MX9804108A (fr)
NO (1)	NO311213B1 (fr)
OA (1)	OA11011A (fr)
PL (1)	PL326928A1 (fr)
SK (1)	SK66898A3 (fr)
TR (1)	TR199800883T2 (fr)
TW (1)	TW409123B (fr)
UY (2)	UY24375A1 (fr)
WO (1)	WO1997019926A1 (fr)

Families Citing this family (48)

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Publication number	Priority date	Publication date	Assignee	Title
EP0983243B1 (fr) *	1997-03-14	2004-06-16	Smithkline Beecham Corporation	Nouveaux quinoline- et naphthalenecarboxamides, compositions pharmaceutiques et procedes d'inhibition de la calpaine
IL133036A0 (en) *	1997-05-23	2001-03-19	Smithkline Beecham Spa	Quinoline-4-carboxamide derivatives as nk-2 and nk-3 receptor antagonists
US6339089B2 (en) *	1997-08-13	2002-01-15	Fujirebio Inc.	Pyrimidine nucleus-containing compound and a medicament containing the same for a blood oxygen partial pressure amelioration, and a method for preparing the same
US6262070B1 (en)	1998-11-04	2001-07-17	Darwin Discovery Ltd.	Heterocyclic compounds and their therapeutic use
GB9825554D0 (en)	1998-11-20	1999-01-13	Smithkline Beecham Spa	Novel Compounds
WO2000031037A1 (fr) *	1998-11-20	2000-06-02	Smithkline Beecham S.P.A.	Derives de quinoline-4-carboxamide utilises comme antagonistes des recepteurs nk-3 et nk-2
US6780875B2 (en) *	1998-11-20	2004-08-24	Smithkline Beecham S.P.A.	Quinoline-4-carboxamide derivatives as NK-3 and NK-2 receptor antagonists
DE60045564D1 (de) *	1999-02-24	2011-03-03	Hoffmann La Roche	4-Phenylpyridinderivate und deren Verwendung als NK-1 Rezeptorantagonisten
US7037922B1 (en)	2000-03-10	2006-05-02	Neurogen Corporation	Aryl fused 2,4-disubstituted pyridines: NK3 receptor ligands
AU4007900A (en) *	1999-03-11	2000-10-16	Neurogen Corporation	Aryl fused 2,4-disubstituted pyridines: nk3 receptor ligands
EP1165542B1 (fr)	1999-03-29	2003-08-20	Neurogen Corporation	Derives de quinoline substitues en position 4 en tant que ligands des recepteurs nk-3 et/ou gaba(a)
AU4802500A (en)	1999-04-26	2000-11-10	Neurogen Corporation	2-aminoquinolinecarboxamides: neurokinin receptor ligands
TWI259180B (en) *	2000-08-08	2006-08-01	Hoffmann La Roche	4-Phenyl-pyridine derivatives
WO2002013825A1 (fr) *	2000-08-11	2002-02-21	Smithkline Beecham P.L.C.	Nouvelle utilisation pharmaceutique de dérivés quinnoliniques
JP2004517062A (ja) *	2000-11-13	2004-06-10	グラクソスミスクライン・ソシエタ・ペル・アチオニ	Ｎｋ−３およびｎｋ−２アンタゴニストとしてのキノリン誘導体
GB0028964D0 (en) *	2000-11-28	2001-01-10	Smithkline Beecham Spa	Novel compounds
US6540733B2 (en)	2000-12-29	2003-04-01	Corazon Technologies, Inc.	Proton generating catheters and methods for their use in enhancing fluid flow through a vascular site occupied by a calcified vascular occlusion
GB0109122D0 (en) *	2001-04-11	2001-05-30	Smithkline Beecham Spa	Novel compounds
ATE313539T1 (de) *	2001-04-11	2006-01-15	Glaxosmithkline Spa	Chinolin-4-carboxamidderivate als nk-3 und nk-2 rezeptor antagonisten
MY134211A (en) *	2001-05-18	2007-11-30	Smithkline Beecham Corp	Novel use
JPWO2004002484A1 (ja) *	2002-06-26	2005-10-27	協和醗酵工業株式会社	ホスホジエステラーゼ阻害剤
GB0312609D0 (en)	2003-06-02	2003-07-09	Astrazeneca Ab	Novel compounds
EP1635834A4 (fr) *	2003-06-25	2009-12-02	Smithkline Beecham Corp	Nouveaux composes
US7288658B2 (en)	2003-07-15	2007-10-30	Hoffmann-La Roche Inc.	Process for preparation of pyridine derivatives
SE0302139D0 (sv) *	2003-07-28	2003-07-28	Astrazeneca Ab	Novel compounds
GB0318727D0 (en) *	2003-08-08	2003-09-10	Smithkline Beecham Corp	Novel compounds
GB0425077D0 (en) *	2004-11-12	2004-12-15	Smithkline Beecham Corp	Novel compounds
WO2006130080A2 (fr) *	2005-06-03	2006-12-07	Astrazeneca Ab	Derives de quinoline utilises comme antagonistes de nk3
CA2613001A1 (fr) *	2005-06-23	2006-12-28	Astrazeneca Ab	Esters de quinoline-3-sulfonate en tant que regulateurs de recepteurs nk3
GB0515580D0 (en)	2005-07-29	2005-09-07	Merck Sharp & Dohme	Therapeutic compounds
WO2007018465A1 (fr) *	2005-08-11	2007-02-15	Astrazeneca Ab	Amide alkyl pyridiyl quinolines en tant que modulateurs du récepteur des nk3
JP2009504642A (ja) *	2005-08-11	2009-02-05	アストラゼネカ・アクチエボラーグ	Ｎｋ−３受容体の調節剤としてのオキソピリジルキノリンアミド
EP1915361A1 (fr) *	2005-08-11	2008-04-30	AstraZeneca AB	Alkylpyridyl quinolines en tant que modulateurs du récepteur des nk3
AR057130A1 (es)	2005-09-21	2007-11-14	Astrazeneca Ab	Quinolinas de alquilsulfoxido y una composicion farmaceutica
AR058051A1 (es) *	2005-09-21	2008-01-23	Astrazeneca Ab	Quinolinas de alquilnitrilo.proceso de obtencion y composiciones farmaceuticas.
TW200804288A (en) *	2005-12-12	2008-01-16	Astrazeneca Ab	Alkylsulphonamide quinolines
PE20091225A1 (es)	2007-03-22	2009-09-16	Astrazeneca Ab	Derivados de quinolina como antagonistas del receptor p2x7
PE20091036A1 (es)	2007-11-30	2009-08-15	Astrazeneca Ab	Derivado de quinolina como antagonista del receptor p2x7
CN102924375B (zh) *	2012-06-21	2015-02-18	江苏恩华药业股份有限公司	Talnetant中间体及其制备方法和应用
CA2909752A1 (fr)	2013-04-19	2014-10-23	Astrazeneca Ab	Compose antagoniste du recepteur nk3 (nk3ra) utilise dans une methode pour traiter le syndrome des ovaires polykystiques (sopk)
CN107074773A (zh)	2014-09-09	2017-08-18	拜耳制药股份公司	取代的n,2‑二芳基喹啉‑4‑甲酰胺及其用途
JP2018512404A (ja)	2015-03-18	2018-05-17	バイエルファーマアクチエンゲゼルシャフト	置換ｎ−ビシクロ−２−アリール−キノリン−４−カルボキサミドおよびその使用
WO2017072629A1 (fr)	2015-10-29	2017-05-04	Cadila Healthcare Limited	Combinaison pharmaceutique d'antagoniste du récepteur nk3 et de biguanides
WO2017153235A1 (fr)	2016-03-09	2017-09-14	Bayer Pharma Aktiengesellschaft	N-cyclo-3-aryl-1-naphthamides substitués et leur utilisation
WO2017153231A1 (fr)	2016-03-09	2017-09-14	Bayer Pharma Aktiengesellschaft	N-cyclo-2-arylisochinolinon-4-carboxamides substitués et leur utilisation
WO2017153234A1 (fr)	2016-03-09	2017-09-14	Bayer Pharma Aktiengesellschaft	N-cyclo-2-arylchinolin-4-carboxamides substitués et leur utilisation
TWI770157B (zh)	2017-04-10	2022-07-11	德商拜耳廠股份有限公司	經取代之n-芳基乙基-2-胺基喹啉-4-甲醯胺及其用途
AU2018251758B2 (en) *	2017-04-10	2021-11-18	Bayer Aktiengesellschaft	Substituted N-arylethyl-2-arylquinoline-4-carboxamides and use thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2538388B1 (fr) *	1982-12-24	1985-06-21	Pharmuka Lab	Nouveaux derives de naphtalene- ou azanaphtalenecarboxamide, leurs procedes de preparation et leur utilisation comme medicaments
DK623586A (da) *	1985-12-27	1987-06-28	Eisai Co Ltd	Piperidinderivater eller salte deraf og farmaceutiske kompositioner indeholdende forbindelserne
ATE161530T1 (de) *	1992-09-04	1998-01-15	Takeda Chemical Industries Ltd	Kondensierte heterozyklische verbindungen, deren herstellung und verwendung
ES2227769T3 (es) *	1994-05-27	2005-04-01	Glaxosmithkline S.P.A.	Derivados de quinolina como antagonistas del receptor nk3 de taquiquinina.
IT1270615B (it) *	1994-07-14	1997-05-07	Smithkline Beecham Farma	Uso di derivati di chinolina

1996
- 1996-11-21 AR ARP960105282A patent/AR004735A1/es unknown
- 1996-11-22 EA EA199800538A patent/EA001771B1/ru not_active IP Right Cessation
- 1996-11-22 PL PL96326928A patent/PL326928A1/xx unknown
- 1996-11-22 MA MA24399A patent/MA24011A1/fr unknown
- 1996-11-22 CZ CZ981580A patent/CZ158098A3/cs unknown
- 1996-11-22 SK SK668-98A patent/SK66898A3/sk unknown
- 1996-11-22 HU HU9901016A patent/HUP9901016A3/hu unknown
- 1996-11-22 WO PCT/EP1996/005207 patent/WO1997019926A1/fr not_active Ceased
- 1996-11-22 IL IL12441896A patent/IL124418A0/xx unknown
- 1996-11-22 KR KR1019980703874A patent/KR19990071598A/ko not_active Withdrawn
- 1996-11-22 JP JP09520158A patent/JP2000513325A/ja active Pending
- 1996-11-22 CA CA002238328A patent/CA2238328A1/fr not_active Abandoned
- 1996-11-22 CN CN96199747A patent/CN1207729A/zh active Pending
- 1996-11-22 AU AU10318/97A patent/AU1031897A/en not_active Abandoned
- 1996-11-22 BR BR9611757A patent/BR9611757A/pt unknown
- 1996-11-22 AP APAP/P/1998/001238A patent/AP9801238A0/en unknown
- 1996-11-22 TR TR1998/00883T patent/TR199800883T2/xx unknown
- 1996-11-22 UY UY24375A patent/UY24375A1/es not_active IP Right Cessation
- 1996-11-22 EP EP96941025A patent/EP1019377A1/fr not_active Withdrawn
- 1996-11-23 TW TW085114501A patent/TW409123B/zh not_active IP Right Cessation
- 1996-11-23 DZ DZ960173A patent/DZ2128A1/fr active
1997
- 1997-05-16 UY UY24555A patent/UY24555A1/es not_active Application Discontinuation
1998
- 1998-05-22 OA OA9800062A patent/OA11011A/en unknown
- 1998-05-22 NO NO19982333A patent/NO311213B1/no not_active IP Right Cessation
- 1998-05-22 MX MX9804108A patent/MX9804108A/es unknown
- 1998-06-18 BG BG102557A patent/BG102557A/bg unknown
2001
- 2001-11-26 US US09/994,402 patent/US20020068827A1/en not_active Abandoned

Also Published As

Publication number	Publication date
IL124418A0 (en)	1998-12-06
MX9804108A (es)	1998-09-30
CA2238328A1 (fr)	1997-06-05
EP1019377A1 (fr)	2000-07-19
UY24375A1 (es)	1997-05-22
NO311213B1 (no)	2001-10-29
AP9801238A0 (en)	1998-06-30
PL326928A1 (en)	1998-11-09
WO1997019926A1 (fr)	1997-06-05
EA001771B1 (ru)	2001-08-27
AU1031897A (en)	1997-06-19
HUP9901016A2 (hu)	2000-03-28
CZ158098A3 (cs)	1998-10-14
KR19990071598A (ko)	1999-09-27
DZ2128A1 (fr)	2002-10-26
NO982333L (no)	1998-07-22
AR004735A1 (es)	1999-03-10
TW409123B (en)	2000-10-21
CN1207729A (zh)	1999-02-10
HUP9901016A3 (en)	2002-01-28
UY24555A1 (es)	2001-04-30
SK66898A3 (en)	1998-12-02
BR9611757A (pt)	1999-04-06
JP2000513325A (ja)	2000-10-10
BG102557A (bg)	1999-03-31
NO982333D0 (no)	1998-05-22
TR199800883T2 (xx)	2000-12-21
US20020068827A1 (en)	2002-06-06
MA24011A1 (fr)	1997-07-01
EA199800538A1 (ru)	1998-12-24

Publication	Publication Date	Title
OA11011A (en)	2003-03-06	Quinoline-4-carboxamide derivatives their preparation and their use as neurokin 3 (nk-3)-and neurokin 2 (nk-2)receptor antagonists
US6277862B1 (en)	2001-08-21	Quinoline derivatives
WO1997021680A9 (fr)	1997-09-12	Derives de quinoline
EP1377555B1 (fr)	2007-01-24	Un derive de dioxino[2,3-g]quinoline-9-acide carboxylique en tant qu'antagoniste du recepteur nk3
NZ511777A (en)	2003-12-19	Quinoline-4-carboxamide derivatives as NK-3 and NK-2 receptor antagonists
EP0983262B1 (fr)	2003-07-09	Derives de quinoline-4-carboxamide comme antagonistes des recepteurs nk-2 et nk-3
EP1385839B1 (fr)	2006-02-22	Derives de 3-substitue quinoline-4-carboxamide utilises comme antagonistes du recepteur nk3 et du recepteur nk2
EP1131294B1 (fr)	2006-12-20	Derives de quinoline utilises comme ligands des recepteurs nk-2 et nk-3
US20040077658A1 (en)	2004-04-22	Quinoline-4-carboxamide derivatives as nk-3 and nk-2 receptor antagonists
US6780875B2 (en)	2004-08-24	Quinoline-4-carboxamide derivatives as NK-3 and NK-2 receptor antagonists
US20070197546A1 (en)	2007-08-23	Quinoline-4-carboxamide as nk-2 and nk-3 receptor antagonists
AU4263200A (en)	2000-11-30	Quinoline-4-carboxamide derivatives, their preparation and their use as neurokinin 3 (NK-3)- and neurokinin 2 (NK-2) receptor antagonists
Luca et al.	0	PCT WORLD) INTELLECTUAL PROPERTY ORGANIZATION
AU1031797A (en)	1997-07-03	Quinoline derivatives
KR20010012823A (ko)	2001-02-26	Ｎｋ-2 및 ｎｋ-3 수용체 길항제로서의퀴놀린-4-카르복스아미드 유도체
AU3541300A (en)	2000-08-03	Quinoline derivatives
MXPA99010841A (en)	2000-07-01	Quinoline-4-carboxamide derivatives as nk-2 and nk-3 receptor antagonists
CZ416199A3 (cs)	2000-08-16	Chinolin-4-karboxamidové deriváty jako antagonisté receptoru pro NK-2 a NK-3