BG102557A - Производни на хинолин-4-карбоксамиди, метод за получаването им и използването им като антагонисти на неврокинин 3 / nк-/ и неврокинин 2 / nк-/ рецепторите - Google Patents

Производни на хинолин-4-карбоксамиди, метод за получаването им и използването им като антагонисти на неврокинин 3 / nк-/ и неврокинин 2 / nк-/ рецепторите Download PDF

Info

Publication number: BG102557A
Authority: BG; Bulgaria
Prior art keywords: compound; formula; alkyl; group; mmol
Prior art date: 1995-11-24

Application number

BG102557A

Other languages

Bulgarian (bg)

English (en)

Inventor

Giuseppe Giardina

Mario Grugni

Luca Raveglia

Carlo Farina

Original Assignee

Smithkline Beecham S.P.A.

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

1998-06-18

Publication date

1999-03-31

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

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

1998-06-18 Application filed by Smithkline Beecham S.P.A. filed Critical Smithkline Beecham S.P.A.

1999-03-31 Publication of BG102557A publication Critical patent/BG102557A/bg

Links

238000000034 method Methods 0.000 title claims description 30
238000002360 preparation method Methods 0.000 title claims description 14
102100024304 Protachykinin-1 Human genes 0.000 title description 3
239000002464 receptor antagonist Substances 0.000 title description 3
229940044551 receptor antagonist Drugs 0.000 title description 3
LEWDKQKVAFOMPI-UHFFFAOYSA-N quinoline-4-carboxamide Chemical class C1=CC=C2C(C(=O)N)=CC=NC2=C1 LEWDKQKVAFOMPI-UHFFFAOYSA-N 0.000 title description 2
101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 262
-1 C1-6alkenyl Chemical group 0.000 claims abstract description 82
150000003839 salts Chemical class 0.000 claims abstract description 40
125000000217 alkyl group Chemical group 0.000 claims abstract description 29
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 27
239000012453 solvate Substances 0.000 claims abstract description 27
125000003118 aryl group Chemical group 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
229910052736 halogen Inorganic materials 0.000 claims abstract description 18
150000002367 halogens Chemical class 0.000 claims abstract description 18
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
125000005842 heteroatom Chemical group 0.000 claims abstract description 8
229910052799 carbon Inorganic materials 0.000 claims abstract description 7
125000003277 amino group Chemical group 0.000 claims abstract description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
125000005544 phthalimido group Chemical group 0.000 claims abstract description 5
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 3
125000004945 acylaminoalkyl group Chemical group 0.000 claims abstract description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
125000004423 acyloxy group Chemical group 0.000 claims abstract 2
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims abstract 2
125000000623 heterocyclic group Chemical group 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 10
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229910052757 nitrogen Inorganic materials 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000002837 carbocyclic group Chemical group 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000001188 haloalkyl group Chemical group 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
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230000008569 process Effects 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
238000011321 prophylaxis Methods 0.000 claims description 4
230000001225 therapeutic effect Effects 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
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125000004663 dialkyl amino group Chemical group 0.000 claims description 2
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238000004519 manufacturing process Methods 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
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 15
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 3
125000005236 alkanoylamino group Chemical group 0.000 abstract description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 abstract 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 abstract 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
125000000278 alkyl amino alkyl group Chemical group 0.000 abstract 1
125000004093 cyano group Chemical group *C#N 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
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239000000203 mixture Substances 0.000 description 96
239000000243 solution Substances 0.000 description 85
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 82
235000019439 ethyl acetate Nutrition 0.000 description 75
239000011541 reaction mixture Substances 0.000 description 57
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239000003480 eluent Substances 0.000 description 45
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
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229910002027 silica gel Inorganic materials 0.000 description 41
238000006243 chemical reaction Methods 0.000 description 40
239000000460 chlorine Substances 0.000 description 39
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
238000003818 flash chromatography Methods 0.000 description 35
238000005160 1H NMR spectroscopy Methods 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 33
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000012043 crude product Substances 0.000 description 26
239000012044 organic layer Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 21
229920006395 saturated elastomer Polymers 0.000 description 20
239000000047 product Substances 0.000 description 18
239000011734 sodium Substances 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
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235000011114 ammonium hydroxide Nutrition 0.000 description 15
238000000921 elemental analysis Methods 0.000 description 15
229910052938 sodium sulfate Inorganic materials 0.000 description 15
235000011152 sodium sulphate Nutrition 0.000 description 15
239000012299 nitrogen atmosphere Substances 0.000 description 13
238000010992 reflux Methods 0.000 description 13
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
239000003208 petroleum Substances 0.000 description 11
125000006413 ring segment Chemical group 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
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230000000694 effects Effects 0.000 description 9
235000019441 ethanol Nutrition 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000000725 suspension Substances 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
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 8
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238000005481 NMR spectroscopy Methods 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
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208000035475 disorder Diseases 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
ABPUPHVEUMCNPO-QFIPXVFZSA-N 3-(2-aminoethoxy)-2-phenyl-n-[(1s)-1-phenylpropyl]quinoline-4-carboxamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(OCCN)C=1C1=CC=CC=C1 ABPUPHVEUMCNPO-QFIPXVFZSA-N 0.000 description 7
230000003197 catalytic effect Effects 0.000 description 7
238000000354 decomposition reaction Methods 0.000 description 7
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils 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
AOLMGSAMTRTYEX-UHFFFAOYSA-N 2-phenylquinoline-4-carboxamide Chemical compound N=1C2=CC=CC=C2C(C(=O)N)=CC=1C1=CC=CC=C1 AOLMGSAMTRTYEX-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
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IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
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150000003141 primary amines Chemical class 0.000 description 6
108090000765 processed proteins & peptides Proteins 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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KFXNVYYLWUVEAO-UHFFFAOYSA-N 3-methyl-2-phenylquinoline-4-carbonyl chloride Chemical compound N1=C2C=CC=CC2=C(C(Cl)=O)C(C)=C1C1=CC=CC=C1 KFXNVYYLWUVEAO-UHFFFAOYSA-N 0.000 description 4
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206010039083 rhinitis Diseases 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
238000007789 sealing Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
230000020341 sensory perception of pain Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000002466 tachykinin receptor agonist Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
230000002455 vasospastic effect Effects 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1

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)

BG102557A 1995-11-24 1998-06-18 Производни на хинолин-4-карбоксамиди, метод за получаването им и използването им като антагонисти на неврокинин 3 / nк-/ и неврокинин 2 / nк-/ рецепторите BG102557A (bg)

Applications Claiming Priority (3)

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
PCT/EP1996/005207 WO1997019926A1 (fr)	1995-11-24	1996-11-22	Nouveaux derives de quinoline-4-carboxamide, leur preparation et leur utilisation en tant qu'antagonistes des recepteurs des neurokinines 3 (nk-3) et des neurokinines 2 (nk-2)

Publications (1)

Publication Number	Publication Date
BG102557A true BG102557A (bg)	1999-03-31

Family

ID=26331327

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG102557A BG102557A (bg)	1995-11-24	1998-06-18	Производни на хинолин-4-карбоксамиди, метод за получаването им и използването им като антагонисти на неврокинин 3 / nк-/ и неврокинин 2 / nк-/ рецепторите

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)

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CN1264378A (zh) *	1997-05-23	2000-08-23	史密丝克莱恩比彻姆股份公司	作为nk－2和nk－3受体拮抗剂的喹啉－4－甲酰胺衍生物
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
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
JP2002530377A (ja) *	1998-11-20	2002-09-17	スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ	Ｎｋ−３およびｎｋ−２受容体アンタゴニストとしてのキノリン−４−カルボキシアミド誘導体
EP1035115B1 (fr) *	1999-02-24	2004-09-29	F. Hoffmann-La Roche Ag	Dérivés de 4-phenylpyridine et leur utilisation comme antagonistes du recepteur NK-1
US7037922B1 (en)	2000-03-10	2006-05-02	Neurogen Corporation	Aryl fused 2,4-disubstituted pyridines: NK3 receptor ligands
DE60003899T2 (de) *	1999-03-11	2004-05-27	Neurogen Corp., Branford	Aryl-annellierte disubstituierte pyridine : nk3 rezeptor-liganden
ATE247652T1 (de)	1999-03-29	2003-09-15	Neurogen Corp	4-substituierte chinolinderivate als nk-3 und/oder gaba(a) rezeptor liganden
WO2000064877A1 (fr) *	1999-04-26	2000-11-02	Neurogen Corporation	2-aminoquinolinecarboxamides: ligands de recepteurs de la neurokinine
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
EP1334089A1 (fr) *	2000-11-13	2003-08-13	GlaxoSmithKline S.p.A.	Derives de la quinoline en tant qu'antagonistes de nk-3 et nk-2
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
EP1385839B1 (fr) *	2001-04-11	2006-02-22	GlaxoSmithKline S.p.A.	Derives de 3-substitue quinoline-4-carboxamide utilises comme antagonistes du recepteur nk3 et du recepteur nk2
GB0109122D0 (en) *	2001-04-11	2001-05-30	Smithkline Beecham Spa	Novel compounds
MY134211A (en) *	2001-05-18	2007-11-30	Smithkline Beecham Corp	Novel use
EP1541149A1 (fr) *	2002-06-26	2005-06-15	Kyowa Hakko Kogyo Co., Ltd.	Inhibiteur de phosphodiesterase
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
CA2611060A1 (fr) *	2005-06-03	2006-12-07	R. Thomas Simpson	Derives de quinoline utilises comme antagonistes de nk3
WO2006137789A1 (fr) *	2005-06-23	2006-12-28	Astrazeneca Ab	Esters de quinoline-3-sulfonate en tant que régulateurs de récepteurs nk3
GB0515580D0 (en)	2005-07-29	2005-09-07	Merck Sharp & Dohme	Therapeutic compounds
CN101282961A (zh) *	2005-08-11	2008-10-08	阿斯利康(瑞典)有限公司	作为nk3受体调节剂的烷基吡啶基喹啉
US20080280949A1 (en) *	2005-08-11	2008-11-13	Astrazeneca Ab	Oxopyridyl Quinoline Amides as Nk3 Receptor Modulators
WO2007018465A1 (fr) *	2005-08-11	2007-02-15	Astrazeneca Ab	Amide alkyl pyridiyl quinolines en tant que modulateurs du récepteur des nk3
AR058051A1 (es) *	2005-09-21	2008-01-23	Astrazeneca Ab	Quinolinas de alquilnitrilo.proceso de obtencion y composiciones farmaceuticas.
AR057130A1 (es)	2005-09-21	2007-11-14	Astrazeneca Ab	Quinolinas de alquilsulfoxido y una composicion farmaceutica
TW201018662A (en)	2005-12-12	2010-05-16	Astrazeneca Ab	Alkylsulphonamide quinolines
RU2460727C2 (ru)	2007-03-22	2012-09-10	Астразенека Аб	Хинолиновые производные для лечения воспалительных заболеваний
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
BR112015026519A2 (pt)	2013-04-19	2017-07-25	Astrazeneca Ab	composto antagonista do receptor nk3 (nk3ra) para uso em um método destinado ao tratamento de síndrome do ovário policístico (sop)
US10189788B2 (en)	2014-09-09	2019-01-29	Bayer Pharma Aktiengesellschaft	Substituted N,2-diarylquinoline-4-carboxamides and the use thereof as anti-inflammatory agents
EP3271334A1 (fr)	2015-03-18	2018-01-24	Bayer Pharma Aktiengesellschaft	N-bicyclo-2-arylchinolino-4-carboxamides substitués et leur utilisation
WO2017072629A1 (fr)	2015-10-29	2017-05-04	Cadila Healthcare Limited	Combinaison pharmaceutique d'antagoniste du récepteur nk3 et de biguanides
WO2017153234A1 (fr)	2016-03-09	2017-09-14	Bayer Pharma Aktiengesellschaft	N-cyclo-2-arylchinolin-4-carboxamides substitués et leur utilisation
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
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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 MA MA24399A patent/MA24011A1/fr unknown
- 1996-11-22 KR KR1019980703874A patent/KR19990071598A/ko not_active Withdrawn
- 1996-11-22 AP APAP/P/1998/001238A patent/AP9801238A0/en unknown
- 1996-11-22 WO PCT/EP1996/005207 patent/WO1997019926A1/fr not_active Ceased
- 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 SK SK668-98A patent/SK66898A3/sk unknown
- 1996-11-22 EP EP96941025A patent/EP1019377A1/fr not_active Withdrawn
- 1996-11-22 PL PL96326928A patent/PL326928A1/xx unknown
- 1996-11-22 JP JP09520158A patent/JP2000513325A/ja active Pending
- 1996-11-22 UY UY24375A patent/UY24375A1/es not_active IP Right Cessation
- 1996-11-22 CZ CZ981580A patent/CZ158098A3/cs unknown
- 1996-11-22 IL IL12441896A patent/IL124418A0/xx unknown
- 1996-11-22 TR TR1998/00883T patent/TR199800883T2/xx unknown
- 1996-11-22 HU HU9901016A patent/HUP9901016A3/hu unknown
- 1996-11-22 EA EA199800538A patent/EA001771B1/ru not_active IP Right Cessation
- 1996-11-22 CA CA002238328A patent/CA2238328A1/fr not_active Abandoned
- 1996-11-22 BR BR9611757A patent/BR9611757A/pt unknown
- 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 MX MX9804108A patent/MX9804108A/es unknown
- 1998-05-22 OA OA9800062A patent/OA11011A/en unknown
- 1998-05-22 NO NO19982333A patent/NO311213B1/no not_active IP Right Cessation
- 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
BR9611757A (pt)	1999-04-06
MA24011A1 (fr)	1997-07-01
WO1997019926A1 (fr)	1997-06-05
HUP9901016A2 (hu)	2000-03-28
NO311213B1 (no)	2001-10-29
IL124418A0 (en)	1998-12-06
JP2000513325A (ja)	2000-10-10
US20020068827A1 (en)	2002-06-06
CA2238328A1 (fr)	1997-06-05
EP1019377A1 (fr)	2000-07-19
AR004735A1 (es)	1999-03-10
UY24375A1 (es)	1997-05-22
PL326928A1 (en)	1998-11-09
CN1207729A (zh)	1999-02-10
AU1031897A (en)	1997-06-19
AP9801238A0 (en)	1998-06-30
OA11011A (en)	2003-03-06
HUP9901016A3 (en)	2002-01-28
NO982333D0 (no)	1998-05-22
TW409123B (en)	2000-10-21
MX9804108A (es)	1998-09-30
DZ2128A1 (fr)	2002-10-26
UY24555A1 (es)	2001-04-30
EA001771B1 (ru)	2001-08-27
CZ158098A3 (cs)	1998-10-14
TR199800883T2 (xx)	2000-12-21
EA199800538A1 (ru)	1998-12-24
KR19990071598A (ko)	1999-09-27
NO982333L (no)	1998-07-22
SK66898A3 (en)	1998-12-02

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