IL128631A - Derivatives of acetylaminoalkenylene-amide as 1 NK and 2 NK antagonists - Google Patents

Derivatives of acetylaminoalkenylene-amide as 1 NK and 2 NK antagonists

Info

Publication number: IL128631A
Authority: IL; Israel
Prior art keywords: phenyl; methyl; hydrogen; lower alkyl; indol
Prior art date: 1996-08-22

Application number

IL12863197A

Other languages

English (en)

Hebrew (he)

Other versions

IL128631A0 (en

Original Assignee

Novartis Ag

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.)

1996-08-22

Filing date

1997-08-13

Publication date

2002-09-12

1997-08-13 Application filed by Novartis Ag filed Critical Novartis Ag

2000-01-31 Publication of IL128631A0 publication Critical patent/IL128631A0/xx

2002-09-12 Publication of IL128631A publication Critical patent/IL128631A/en

Links

239000005557 antagonist Substances 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 132
239000001257 hydrogen Substances 0.000 claims abstract description 45
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 45
150000003839 salts Chemical class 0.000 claims abstract description 40
125000000217 alkyl group Chemical group 0.000 claims abstract description 32
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
201000010099 disease Diseases 0.000 claims abstract description 19
150000002431 hydrogen Chemical group 0.000 claims abstract description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 11
150000002367 halogens Chemical class 0.000 claims abstract description 11
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
125000001424 substituent group Chemical group 0.000 claims abstract description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 4
125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 57
-1 3,5-bistrifluoromethyl-phenyl Chemical group 0.000 claims description 38
239000002253 acid Substances 0.000 claims description 33
238000000034 method Methods 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
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 8
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 7
108010040722 Neurokinin-2 Receptors Proteins 0.000 claims description 7
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 7
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 6
108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 6
241000282414 Homo sapiens Species 0.000 claims description 5
102100037342 Substance-K receptor Human genes 0.000 claims description 5
102100037346 Substance-P receptor Human genes 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
BOWUOGIPSRVRSJ-YFKPBYRVSA-N L-2-aminohexano-6-lactam Chemical compound N[C@H]1CCCCNC1=O BOWUOGIPSRVRSJ-YFKPBYRVSA-N 0.000 claims description 4
150000001735 carboxylic acids Chemical class 0.000 claims description 4
125000005059 halophenyl group Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
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 3
230000001225 therapeutic effect Effects 0.000 claims description 3
125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 claims description 2
230000008485 antagonism Effects 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
208000006673 asthma Diseases 0.000 abstract description 6
239000000126 substance Substances 0.000 abstract description 6
102000003141 Tachykinin Human genes 0.000 abstract description 5
208000035475 disorder Diseases 0.000 abstract description 5
108060008037 tachykinin Proteins 0.000 abstract description 5
230000002685 pulmonary effect Effects 0.000 abstract description 4
208000019901 Anxiety disease Diseases 0.000 abstract description 3
206010006458 Bronchitis chronic Diseases 0.000 abstract description 3
208000011231 Crohn disease Diseases 0.000 abstract description 3
206010020772 Hypertension Diseases 0.000 abstract description 3
208000019695 Migraine disease Diseases 0.000 abstract description 3
208000002193 Pain Diseases 0.000 abstract description 3
206010047700 Vomiting Diseases 0.000 abstract description 3
208000026935 allergic disease Diseases 0.000 abstract description 3
206010006451 bronchitis Diseases 0.000 abstract description 3
210000003169 central nervous system Anatomy 0.000 abstract description 3
208000007451 chronic bronchitis Diseases 0.000 abstract description 3
208000027866 inflammatory disease Diseases 0.000 abstract description 3
206010027599 migraine Diseases 0.000 abstract description 3
201000003883 Cystic fibrosis Diseases 0.000 abstract description 2
206010012735 Diarrhoea Diseases 0.000 abstract description 2
206010019233 Headaches Diseases 0.000 abstract description 2
206010020751 Hypersensitivity Diseases 0.000 abstract description 2
206010025477 Malabsorption conditions Diseases 0.000 abstract description 2
206010027476 Metastases Diseases 0.000 abstract description 2
208000006011 Stroke Diseases 0.000 abstract description 2
201000009961 allergic asthma Diseases 0.000 abstract description 2
230000000172 allergic effect Effects 0.000 abstract description 2
230000033115 angiogenesis Effects 0.000 abstract description 2
208000010668 atopic eczema Diseases 0.000 abstract description 2
210000004204 blood vessel Anatomy 0.000 abstract description 2
230000004087 circulation Effects 0.000 abstract description 2
210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
230000009610 hypersensitivity Effects 0.000 abstract description 2
210000000987 immune system Anatomy 0.000 abstract description 2
230000004968 inflammatory condition Effects 0.000 abstract description 2
208000030603 inherited susceptibility to asthma Diseases 0.000 abstract description 2
201000010659 intrinsic asthma Diseases 0.000 abstract description 2
210000003563 lymphoid tissue Anatomy 0.000 abstract description 2
230000004089 microcirculation Effects 0.000 abstract description 2
230000008506 pathogenesis Effects 0.000 abstract description 2
230000007170 pathology Effects 0.000 abstract description 2
210000001428 peripheral nervous system Anatomy 0.000 abstract description 2
208000005069 pulmonary fibrosis Diseases 0.000 abstract description 2
230000003393 splenic effect Effects 0.000 abstract description 2
210000001519 tissue Anatomy 0.000 abstract description 2
230000000472 traumatic effect Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 122
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
239000000243 solution Substances 0.000 description 83
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
238000001704 evaporation Methods 0.000 description 62
230000008020 evaporation Effects 0.000 description 62
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
239000004480 active ingredient Substances 0.000 description 36
235000002639 sodium chloride Nutrition 0.000 description 32
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
239000012074 organic phase Substances 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 20
235000019341 magnesium sulphate Nutrition 0.000 description 20
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
239000000725 suspension Substances 0.000 description 17
239000007858 starting material Substances 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 14
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
239000003921 oil Substances 0.000 description 14
239000006260 foam Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
239000012267 brine Substances 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 11
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 11
239000007787 solid Substances 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
239000002585 base Substances 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
239000001373 (E)-2-methylpent-2-enoic acid Substances 0.000 description 9
WAKMMQSMEDJRRI-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC(C(Cl)=O)=CC(C(F)(F)F)=C1 WAKMMQSMEDJRRI-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
239000008101 lactose Substances 0.000 description 8
XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000003826 tablet Substances 0.000 description 8
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
125000004494 ethyl ester group Chemical group 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000000463 material Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
239000000454 talc Substances 0.000 description 7
229910052623 talc Inorganic materials 0.000 description 7
235000012222 talc Nutrition 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001514 detection method Methods 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
150000004702 methyl esters Chemical class 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
239000008259 solid foam Substances 0.000 description 6
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical class C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
102100024304 Protachykinin-1 Human genes 0.000 description 5
239000013078 crystal Substances 0.000 description 5
NGFQXYLWQODUIL-UHFFFAOYSA-N cyclohexylazanide Chemical compound [NH-]C1CCCCC1 NGFQXYLWQODUIL-UHFFFAOYSA-N 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
229940014259 gelatin Drugs 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
206010006482 Bronchospasm Diseases 0.000 description 4
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
101800003906 Substance P Proteins 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000002775 capsule Substances 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
239000008298 dragée Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
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239000008187 granular material Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000005342 ion exchange Methods 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
229920001592 potato starch Polymers 0.000 description 4
150000003141 primary amines Chemical class 0.000 description 4
239000003380 propellant Substances 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000002904 solvent Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
241000700198 Cavia Species 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 3
101800000399 Neurokinin A Proteins 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
235000013539 calcium stearate Nutrition 0.000 description 3
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LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
210000005095 gastrointestinal system Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000003978 infusion fluid Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
201000004614 iritis Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
IKCXMEOLLZPWBQ-QGZVFWFLSA-N methyl (2r)-2-(4-chlorophenyl)-2-[ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoate Chemical compound CC(C)(C)OC(=O)N(CC)[C@@](C)(C(=O)OC)C1=CC=C(Cl)C=C1 IKCXMEOLLZPWBQ-QGZVFWFLSA-N 0.000 description 1
JZHBYNKCRAKCEK-SNVBAGLBSA-N methyl (2r)-2-[4-chloro-n-[(2-methylpropan-2-yl)oxycarbonyl]anilino]propanoate Chemical compound COC(=O)[C@@H](C)N(C(=O)OC(C)(C)C)C1=CC=C(Cl)C=C1 JZHBYNKCRAKCEK-SNVBAGLBSA-N 0.000 description 1
QXLOVPXUZAOKBL-CQSZACIVSA-N methyl (2r)-3-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC=C2C(C[C@H](C(=O)OC)NC(=O)OC(C)(C)C)=CNC2=C1 QXLOVPXUZAOKBL-CQSZACIVSA-N 0.000 description 1
JGTNJJNKCUGNDP-QGZVFWFLSA-N methyl (2r)-4-(1-methylindol-3-yl)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoate Chemical compound C1=CC=C2C(CC[C@H](C(=O)OC)N(C)C(=O)OC(C)(C)C)=CN(C)C2=C1 JGTNJJNKCUGNDP-QGZVFWFLSA-N 0.000 description 1
JZHBYNKCRAKCEK-JTQLQIEISA-N methyl (2s)-2-[4-chloro-n-[(2-methylpropan-2-yl)oxycarbonyl]anilino]propanoate Chemical compound COC(=O)[C@H](C)N(C(=O)OC(C)(C)C)C1=CC=C(Cl)C=C1 JZHBYNKCRAKCEK-JTQLQIEISA-N 0.000 description 1
XNFNGGQRDXFYMM-PPHPATTJSA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate;hydrochloride Chemical compound Cl.C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 XNFNGGQRDXFYMM-PPHPATTJSA-N 0.000 description 1
HYHJFSYPNDHZFJ-UHFFFAOYSA-N methyl 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3,3-diphenylpropanoate Chemical compound C=1C=CC=CC=1C(C(C(=O)OC)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 HYHJFSYPNDHZFJ-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
244000005700 microbiome Species 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
239000001472 potassium tartrate Substances 0.000 description 1
229940111695 potassium tartrate Drugs 0.000 description 1
235000011005 potassium tartrates Nutrition 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
PAQZWJGSJMLPMG-UHFFFAOYSA-N propylphosphonic anhydride Substances CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
239000002002 slurry Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000001433 sodium tartrate Substances 0.000 description 1
229960002167 sodium tartrate Drugs 0.000 description 1
235000011004 sodium tartrates Nutrition 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000008275 solid aerosol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
ABXZPDMSQNXMMA-UHFFFAOYSA-N tert-butyl n-(3-hydroxy-1,1-diphenylpropan-2-yl)-n-methylcarbamate Chemical compound C=1C=CC=CC=1C(C(CO)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 ABXZPDMSQNXMMA-UHFFFAOYSA-N 0.000 description 1
GZCQENLGVWFTQT-JLOHTSLTSA-N tert-butyl n-[(2r)-1-(4-chlorophenyl)-3-hydroxybutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)C)CC1=CC=C(Cl)C=C1 GZCQENLGVWFTQT-JLOHTSLTSA-N 0.000 description 1
ZPTPYSUACNBCFZ-CYBMUJFWSA-N tert-butyl n-[(2r)-1-(4-chlorophenyl)-3-oxobutan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C(=O)C)CC1=CC=C(Cl)C=C1 ZPTPYSUACNBCFZ-CYBMUJFWSA-N 0.000 description 1
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
HKRXAGGBDLAPEZ-UHFFFAOYSA-N tert-butyl n-methyl-n-(3-oxo-1,1-diphenylpropan-2-yl)carbamate Chemical compound C=1C=CC=CC=1C(C(C=O)N(C)C(=O)OC(C)(C)C)C1=CC=CC=C1 HKRXAGGBDLAPEZ-UHFFFAOYSA-N 0.000 description 1
YNEAFPHVAQJCHJ-CQSZACIVSA-N tert-butyl n-methyl-n-[(2r)-1-(1-methylindol-3-yl)-3-oxopropan-2-yl]carbamate Chemical compound C1=CC=C2C(C[C@@H](N(C)C(=O)OC(C)(C)C)C=O)=CN(C)C2=C1 YNEAFPHVAQJCHJ-CQSZACIVSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
230000000699 topical effect Effects 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
229940078499 tricalcium phosphate Drugs 0.000 description 1
235000019731 tricalcium phosphate Nutrition 0.000 description 1
229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
125000004360 trifluorophenyl group Chemical group 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- 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
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Pulmonology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Neurology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IL12863197A 1996-08-22 1997-08-13 Derivatives of acetylaminoalkenylene-amide as 1 NK and 2 NK antagonists IL128631A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CH206196		1996-08-22
PCT/EP1997/004436 WO1998007694A1 (en)	1996-08-22	1997-08-13	Acylaminoalkenylene-amide derivatives as nk1 and nk2 antagonists

Publications (2)

Publication Number	Publication Date
IL128631A0 IL128631A0 (en)	2000-01-31
IL128631A true IL128631A (en)	2002-09-12

Family

ID=4225003

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12863197A IL128631A (en)	1996-08-22	1997-08-13	Derivatives of acetylaminoalkenylene-amide as 1 NK and 2 NK antagonists

Country Status (31)

Country	Link
US (1)	US6319917B1 (cs)
EP (1)	EP0923550B1 (cs)
JP (1)	JP3654908B2 (cs)
KR (1)	KR100467402B1 (cs)
CN (1)	CN1119328C (cs)
AR (1)	AR009266A1 (cs)
AT (1)	ATE224875T1 (cs)
AU (1)	AU721850B2 (cs)
BR (1)	BR9711350A (cs)
CA (1)	CA2264065C (cs)
CO (1)	CO4900047A1 (cs)
CZ (1)	CZ294233B6 (cs)
DE (1)	DE69715886T2 (cs)
DK (1)	DK0923550T3 (cs)
ES (1)	ES2184083T3 (cs)
HU (1)	HU226395B1 (cs)
ID (1)	ID18059A (cs)
IL (1)	IL128631A (cs)
MY (1)	MY132550A (cs)
NO (1)	NO312292B1 (cs)
NZ (1)	NZ334736A (cs)
PE (1)	PE107498A1 (cs)
PL (1)	PL193731B1 (cs)
PT (1)	PT923550E (cs)
RU (1)	RU2185375C2 (cs)
SI (1)	SI0923550T1 (cs)
SK (1)	SK283991B6 (cs)
TR (1)	TR199900363T2 (cs)
TW (1)	TW438777B (cs)
WO (1)	WO1998007694A1 (cs)
ZA (1)	ZA977493B (cs)

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Publication number	Priority date	Publication date	Assignee	Title
US6281300B1 (en) *	1998-03-20	2001-08-28	Exxon Chemical Patents, Inc.	Continuous slurry polymerization volatile removal
GB0010958D0 (en) *	2000-05-05	2000-06-28	Novartis Ag	Organic compounds
GB0203061D0 (en)	2002-02-08	2002-03-27	Novartis Ag	Organic compounds
GB0224788D0 (en) *	2002-10-24	2002-12-04	Novartis Ag	Organic compounds
GB2394417A (en) *	2002-10-24	2004-04-28	Novartis Ag	Solid dispersion comprising a piperidine substance P antagonist and a carrier
AU2004283038B9 (en) *	2003-10-27	2008-04-24	Novartis Ag	Use of neurokinin antagonists in the treatment of urinary incontinence
JP5248779B2 (ja) *	2003-12-01	2013-07-31	ケンブリッジエンタープライズリミティド	抗炎症剤
RU2365585C2 (ru) *	2003-12-01	2009-08-27	Кембридж Энтерпрайз Лимитед	Противовоспалительные средства
GB0402679D0 (en) *	2004-02-06	2004-03-10	Novartis Ag	Organic compounds
GB0607532D0 (en) *	2006-04-13	2006-05-24	Novartis Ag	Organic compounds
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1997
- 1997-08-08 MY MYPI97003625A patent/MY132550A/en unknown
- 1997-08-13 CA CA002264065A patent/CA2264065C/en not_active Expired - Fee Related
- 1997-08-13 CZ CZ1999581A patent/CZ294233B6/cs not_active IP Right Cessation
- 1997-08-13 SI SI9730413T patent/SI0923550T1/xx unknown
- 1997-08-13 EP EP97918984A patent/EP0923550B1/en not_active Expired - Lifetime
- 1997-08-13 WO PCT/EP1997/004436 patent/WO1998007694A1/en not_active Ceased
- 1997-08-13 PT PT97918984T patent/PT923550E/pt unknown
- 1997-08-13 SK SK221-99A patent/SK283991B6/sk not_active IP Right Cessation
- 1997-08-13 DK DK97918984T patent/DK0923550T3/da active
- 1997-08-13 RU RU99106157/04A patent/RU2185375C2/ru not_active IP Right Cessation
- 1997-08-13 CN CN97198633A patent/CN1119328C/zh not_active Expired - Fee Related
- 1997-08-13 KR KR10-1999-7001487A patent/KR100467402B1/ko not_active Expired - Fee Related
- 1997-08-13 NZ NZ334736A patent/NZ334736A/xx not_active IP Right Cessation
- 1997-08-13 HU HU0001165A patent/HU226395B1/hu not_active IP Right Cessation
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- 1997-08-13 BR BR9711350A patent/BR9711350A/pt not_active IP Right Cessation
- 1997-08-13 DE DE69715886T patent/DE69715886T2/de not_active Expired - Lifetime
- 1997-08-13 JP JP51037198A patent/JP3654908B2/ja not_active Expired - Lifetime
- 1997-08-13 AT AT97918984T patent/ATE224875T1/de active
- 1997-08-13 TR TR1999/00363T patent/TR199900363T2/xx unknown
- 1997-08-13 ES ES97918984T patent/ES2184083T3/es not_active Expired - Lifetime
- 1997-08-13 AU AU42993/97A patent/AU721850B2/en not_active Ceased
- 1997-08-19 AR ARP970103747A patent/AR009266A1/es active IP Right Grant
- 1997-08-20 PE PE1997000741A patent/PE107498A1/es not_active Application Discontinuation
- 1997-08-20 ID IDP972913A patent/ID18059A/id unknown
- 1997-08-21 ZA ZA977493A patent/ZA977493B/xx unknown
- 1997-08-21 CO CO97048265A patent/CO4900047A1/es unknown
- 1997-08-22 TW TW086111854A patent/TW438777B/zh not_active IP Right Cessation
1999
- 1999-02-19 NO NO19990786A patent/NO312292B1/no not_active IP Right Cessation
- 1999-02-19 PL PL97331740A patent/PL193731B1/pl not_active IP Right Cessation
2000
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Also Published As

Publication number	Publication date
MY132550A (en)	2007-10-31
PL193731B1 (pl)	2007-03-30
JP3654908B2 (ja)	2005-06-02
ID18059A (id)	1998-02-26
CN1119328C (zh)	2003-08-27
WO1998007694A1 (en)	1998-02-26
NO312292B1 (no)	2002-04-22
CZ58199A3 (cs)	1999-06-16
AU4299397A (en)	1998-03-06
KR20000068325A (ko)	2000-11-25
US6319917B1 (en)	2001-11-20
PT923550E (pt)	2003-01-31
KR100467402B1 (ko)	2005-01-24
ATE224875T1 (de)	2002-10-15
EP0923550A1 (en)	1999-06-23
AU721850B2 (en)	2000-07-13
RU2185375C2 (ru)	2002-07-20
TR199900363T2 (xx)	1999-04-21
HK1021372A1 (en)	2000-06-09
DE69715886T2 (de)	2003-05-15
ES2184083T3 (es)	2003-04-01
HUP0001165A3 (en)	2002-02-28
PE107498A1 (es)	1999-01-28
SK22199A3 (en)	2000-02-14
JP2001503387A (ja)	2001-03-13
EP0923550B1 (en)	2002-09-25
BR9711350A (pt)	1999-08-17
SK283991B6 (sk)	2004-07-07
CA2264065C (en)	2008-02-05
IL128631A0 (en)	2000-01-31
SI0923550T1 (en)	2003-02-28
NZ334736A (en)	2000-09-29
NO990786D0 (no)	1999-02-19
CZ294233B6 (cs)	2004-11-10
NO990786L (no)	1999-03-25
HUP0001165A2 (hu)	2000-11-28
DE69715886D1 (de)	2002-10-31
DK0923550T3 (da)	2003-01-06
PL331740A1 (en)	1999-08-02
CN1233238A (zh)	1999-10-27
TW438777B (en)	2001-06-07
CA2264065A1 (en)	1998-02-26
AR009266A1 (es)	2000-04-12
ZA977493B (en)	1998-08-03
HU226395B1 (en)	2008-11-28
CO4900047A1 (es)	2000-03-27

Legal Events

Date	Code	Title
2003-02-12	FF	Patent granted
2003-03-12	KB	Patent renewed
2003-10-31	KB	Patent renewed
2007-09-20	KB	Patent renewed
2011-08-31	KB	Patent renewed
2016-03-31	MM9K	Patent not in force due to non-payment of renewal fees

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