IL125578A - N-Methyl - N - 4 - (4 (H1 - Benzimidazole-2 - Eyal - Amino) Pipridine - 1 - Eyal) 2 - (Aryl) Butyl benzamides and pharmaceutical preparations useful for the treatment of allergic diseases - Google Patents

N-Methyl - N - 4 - (4 (H1 - Benzimidazole-2 - Eyal - Amino) Pipridine - 1 - Eyal) 2 - (Aryl) Butyl benzamides and pharmaceutical preparations useful for the treatment of allergic diseases

Info

Publication number: IL125578A
Authority: IL; Israel
Prior art keywords: methyl; butyl; benzimidazol; amino; piperidin
Prior art date: 1996-02-21

Application number

IL12557897A

Other languages

English (en)

Hebrew (he)

Other versions

IL125578A0 (en

Original Assignee

Aventis Pharma Inc

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.)

1996-02-21

Filing date

1997-01-29

Publication date

2002-09-12

1997-01-06 Priority claimed from US08/778,996 external-priority patent/US5922737A/en

1997-01-29 Application filed by Aventis Pharma Inc filed Critical Aventis Pharma Inc

1999-03-12 Publication of IL125578A0 publication Critical patent/IL125578A0/xx

2002-09-12 Publication of IL125578A publication Critical patent/IL125578A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 14
208000026935 allergic disease Diseases 0.000 title description 12
238000011282 treatment Methods 0.000 title description 9
BAULSHLTGVOYKM-UHFFFAOYSA-N n-butylbenzamide Chemical class CCCCNC(=O)C1=CC=CC=C1 BAULSHLTGVOYKM-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 282
239000001257 hydrogen Substances 0.000 claims abstract description 63
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 63
150000002431 hydrogen Chemical class 0.000 claims abstract description 33
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 30
150000003839 salts Chemical class 0.000 claims abstract description 29
150000003254 radicals Chemical class 0.000 claims abstract description 26
229910052736 halogen Inorganic materials 0.000 claims abstract description 24
150000002367 halogens Chemical class 0.000 claims abstract description 24
125000001424 substituent group Chemical group 0.000 claims abstract description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 16
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims abstract description 3
OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 claims abstract description 3
241000009298 Trigla lyra Species 0.000 claims description 74
239000000203 mixture Substances 0.000 claims description 35
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
206010039085 Rhinitis allergic Diseases 0.000 claims description 10
201000010105 allergic rhinitis Diseases 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 7
208000006673 asthma Diseases 0.000 claims description 6
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
101100406879 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) par-2 gene Proteins 0.000 claims description 5
206010047700 Vomiting Diseases 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
239000000969 carrier Substances 0.000 claims description 2
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 2
KANPGOUUYHRSCI-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-[4-[[1-(2-ethoxyethyl)benzimidazol-2-yl]amino]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1NC(CC1)CCN1CCC(C=1C=C(Cl)C(Cl)=CC=1)CN(C)C(=O)C1=CC=CC=C1 KANPGOUUYHRSCI-UHFFFAOYSA-N 0.000 claims 1
VEBZMEGAQMWOTE-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-[4-[[1-(furan-3-yl)benzimidazol-2-yl]amino]piperidin-1-yl]butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)NC=2N(C3=CC=CC=C3N=2)C2=COC=C2)C=2C=CC(F)=CC=2)=C1 VEBZMEGAQMWOTE-UHFFFAOYSA-N 0.000 claims 1
XYHGAPLVRHQOPD-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-[4-[[1-[2-(2,2,2-trifluoroethoxy)ethyl]benzimidazol-2-yl]amino]piperidin-1-yl]butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)NC=2N(C3=CC=CC=C3N=2)CCOCC(F)(F)F)C=2C=CC(F)=CC=2)=C1 XYHGAPLVRHQOPD-UHFFFAOYSA-N 0.000 claims 1
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 360
-1 BUTYL Chemical class 0.000 description 260
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 192
230000015572 biosynthetic process Effects 0.000 description 168
238000003786 synthesis reaction Methods 0.000 description 168
238000000034 method Methods 0.000 description 153
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 142
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 94
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
238000006243 chemical reaction Methods 0.000 description 82
239000000243 solution Substances 0.000 description 79
239000012044 organic layer Substances 0.000 description 71
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
239000011541 reaction mixture Substances 0.000 description 52
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 50
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 42
239000000741 silica gel Substances 0.000 description 42
229910002027 silica gel Inorganic materials 0.000 description 42
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
235000008504 concentrate Nutrition 0.000 description 39
239000012141 concentrate Substances 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
238000010992 reflux Methods 0.000 description 33
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
238000002360 preparation method Methods 0.000 description 29
102000003141 Tachykinin Human genes 0.000 description 28
108060008037 tachykinin Proteins 0.000 description 28
239000010410 layer Substances 0.000 description 26
229920006395 saturated elastomer Polymers 0.000 description 25
239000002904 solvent Substances 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
239000007787 solid Substances 0.000 description 23
239000005557 antagonist Substances 0.000 description 22
239000012267 brine Substances 0.000 description 22
KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 22
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
229960001340 histamine Drugs 0.000 description 21
235000017557 sodium bicarbonate Nutrition 0.000 description 21
229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
201000010099 disease Diseases 0.000 description 19
239000000047 product Substances 0.000 description 19
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
150000001412 amines Chemical class 0.000 description 17
238000001704 evaporation Methods 0.000 description 17
230000008020 evaporation Effects 0.000 description 17
239000012467 final product Substances 0.000 description 17
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 16
239000002585 base Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
238000000605 extraction Methods 0.000 description 16
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 15
239000012359 Methanesulfonyl chloride Substances 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
102100024304 Protachykinin-1 Human genes 0.000 description 15
101800003906 Substance P Proteins 0.000 description 15
230000008485 antagonism Effects 0.000 description 15
239000007864 aqueous solution Substances 0.000 description 15
235000011089 carbon dioxide Nutrition 0.000 description 15
108020003175 receptors Proteins 0.000 description 15
238000001953 recrystallisation Methods 0.000 description 15
238000001665 trituration Methods 0.000 description 15
102000005962 receptors Human genes 0.000 description 14
230000004044 response Effects 0.000 description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
239000012312 sodium hydride Substances 0.000 description 13
229910000104 sodium hydride Inorganic materials 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
238000001914 filtration Methods 0.000 description 12
235000011121 sodium hydroxide Nutrition 0.000 description 12
206010020751 Hypersensitivity Diseases 0.000 description 11
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
230000027455 binding Effects 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000000872 buffer Substances 0.000 description 10
BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 9
235000019270 ammonium chloride Nutrition 0.000 description 9
229960004424 carbon dioxide Drugs 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
238000011534 incubation Methods 0.000 description 9
230000001404 mediated effect Effects 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
238000012360 testing method Methods 0.000 description 9
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 8
208000024780 Urticaria Diseases 0.000 description 8
239000002253 acid Substances 0.000 description 8
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 8
238000010511 deprotection reaction Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000007789 gas Substances 0.000 description 8
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
238000005192 partition Methods 0.000 description 8
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 8
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
GGNMTJKRHHLJHH-UHFFFAOYSA-N Trimethylaethergallussaeure-amid Natural products COC1=CC(C(N)=O)=CC(OC)=C1OC GGNMTJKRHHLJHH-UHFFFAOYSA-N 0.000 description 7
230000007815 allergy Effects 0.000 description 7
239000000975 dye Substances 0.000 description 7
239000002464 receptor antagonist Substances 0.000 description 7
229940044551 receptor antagonist Drugs 0.000 description 7
239000012047 saturated solution Substances 0.000 description 7
206010049153 Allergic sinusitis Diseases 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
208000036284 Rhinitis seasonal Diseases 0.000 description 6
238000003556 assay Methods 0.000 description 6
208000010668 atopic eczema Diseases 0.000 description 6
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
238000001035 drying Methods 0.000 description 6
GQQQULCEHJQUJT-UHFFFAOYSA-N ethyl 4-aminopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N)CC1 GQQQULCEHJQUJT-UHFFFAOYSA-N 0.000 description 6
XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 6
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000000725 suspension Substances 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
239000000443 aerosol Substances 0.000 description 5
239000000556 agonist Substances 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
239000000739 antihistaminic agent Substances 0.000 description 5
201000008937 atopic dermatitis Diseases 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
125000001246 bromo group Chemical group Br* 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000009472 formulation Methods 0.000 description 5
JHJNPOSPVGRIAN-SFHVURJKSA-N n-[3-[(1s)-1-[[6-(3,4-dimethoxyphenyl)pyrazin-2-yl]amino]ethyl]phenyl]-5-methylpyridine-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=CC(N[C@@H](C)C=2C=C(NC(=O)C=3C=C(C)C=NC=3)C=CC=2)=N1 JHJNPOSPVGRIAN-SFHVURJKSA-N 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
235000017550 sodium carbonate Nutrition 0.000 description 5
JLIODMLUNYIRJR-UHFFFAOYSA-N 1-(2-ethoxyethyl)-n-piperidin-4-ylbenzimidazol-2-amine Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1NC1CCNCC1 JLIODMLUNYIRJR-UHFFFAOYSA-N 0.000 description 4
SFOVDSLXFUGAIV-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-n-piperidin-4-ylbenzimidazol-2-amine Chemical compound C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1NC1CCNCC1 SFOVDSLXFUGAIV-UHFFFAOYSA-N 0.000 description 4
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 4
JHQBLYITVCBGTO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C=C1 JHQBLYITVCBGTO-UHFFFAOYSA-N 0.000 description 4
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JLOUWXVUADSGSJ-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxy-2-(4-fluorophenyl)butyl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC(CCO[Si](C)(C)C(C)(C)C)C=2C=CC(F)=CC=2)=C1 JLOUWXVUADSGSJ-UHFFFAOYSA-N 0.000 description 1
OXUKMJWWPSBNKI-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)butyl]-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(CCO[Si](C)(C)C(C)(C)C)CN(C)C(=O)C1=CC=CC=C1 OXUKMJWWPSBNKI-UHFFFAOYSA-N 0.000 description 1
FRXWSUAKZPCFNI-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxy-2-thiophen-2-ylbutyl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC(CCO[Si](C)(C)C(C)(C)C)C=2SC=CC=2)=C1 FRXWSUAKZPCFNI-UHFFFAOYSA-N 0.000 description 1
FVLVBVSILSHUAF-UHFFFAOYSA-N n-benzyl-3,5-dimethyl-n-propan-2-ylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(C(C)C)CC1=CC=CC=C1 FVLVBVSILSHUAF-UHFFFAOYSA-N 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
POVXOWVFLAAVBH-UHFFFAOYSA-N n-formamidoformamide Chemical compound O=CNNC=O POVXOWVFLAAVBH-UHFFFAOYSA-N 0.000 description 1
JYGDAKOITDCICX-UHFFFAOYSA-N n-methyl-n-(4-methylsulfonyl-2-naphthalen-2-ylbutyl)benzamide Chemical compound C=1C=C2C=CC=CC2=CC=1C(CCS(C)(=O)=O)CN(C)C(=O)C1=CC=CC=C1 JYGDAKOITDCICX-UHFFFAOYSA-N 0.000 description 1
XYWCLGXHZBNORK-UHFFFAOYSA-N n-methyl-n-[2-phenyl-4-[4-[[1-(4,4,4-trifluorobutyl)benzimidazol-2-yl]amino]piperidin-1-yl]butyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(CCN1CCC(CC1)NC=1N(C2=CC=CC=C2N=1)CCCC(F)(F)F)C1=CC=CC=C1 XYWCLGXHZBNORK-UHFFFAOYSA-N 0.000 description 1
NKJKTIUDGDQLIH-UHFFFAOYSA-N n-methyl-n-[2-phenyl-4-[4-[[1-(thiophen-2-ylmethyl)benzimidazol-2-yl]amino]piperidin-1-yl]butyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1NC1=NC2=CC=CC=C2N1CC1=CC=CS1 NKJKTIUDGDQLIH-UHFFFAOYSA-N 0.000 description 1
HQBJLKKAHGYHNW-UHFFFAOYSA-N n-methyl-n-[2-pyridin-2-yl-4-[4-[[4-(pyridin-2-ylmethyl)-1h-benzimidazol-2-yl]amino]piperidin-1-yl]butyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1N=CC=CC=1)CCN(CC1)CCC1NC(NC1=CC=C2)=NC1=C2CC1=CC=CC=N1 HQBJLKKAHGYHNW-UHFFFAOYSA-N 0.000 description 1
UZYHJDFPEWRKKQ-UHFFFAOYSA-N n-piperidin-4-yl-1-(2,2,2-trifluoroethyl)benzimidazol-2-amine Chemical compound N=1C2=CC=CC=C2N(CC(F)(F)F)C=1NC1CCNCC1 UZYHJDFPEWRKKQ-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
239000002245 particle Substances 0.000 description 1
238000005453 pelletization Methods 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
229960003910 promethazine Drugs 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
RMSRWCMCEBGEFB-UHFFFAOYSA-N propyl 2-(chloromethyl)benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1CCl RMSRWCMCEBGEFB-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000004224 protection Effects 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000007115 recruitment Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
238000012216 screening Methods 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
230000028327 secretion Effects 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
238000000526 short-path distillation Methods 0.000 description 1
230000016160 smooth muscle contraction Effects 0.000 description 1
206010041232 sneezing Diseases 0.000 description 1
UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
229960002218 sodium chlorite Drugs 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
241000894007 species Species 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
150000003628 tricarboxylic acids Chemical class 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
239000008243 triphasic system Substances 0.000 description 1
230000009959 type I hypersensitivity Effects 0.000 description 1
210000000264 venule Anatomy 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- 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
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- A61P27/16—Otologicals
- 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
- 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
- C07D401/14—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 three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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

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

IL12557897A 1996-02-21 1997-01-29 N-Methyl - N - 4 - (4 (H1 - Benzimidazole-2 - Eyal - Amino) Pipridine - 1 - Eyal) 2 - (Aryl) Butyl benzamides and pharmaceutical preparations useful for the treatment of allergic diseases IL125578A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US60421696A	1996-02-21	1996-02-21
US08/778,996 US5922737A (en)	1996-02-21	1997-01-06	Substituted N-methyl-N-(4-(4-(1H-Benzimidazol-2-YL-amino) piperidin-1-YL)-2-(arlyl) butyl) benzamides useful for the treatment of allergic diseases
PCT/US1997/001571 WO1997030989A1 (en)	1996-02-21	1997-01-29	Novel substituted n-methyl-n-(4-(4-(1h-benzimidazol-2-yl-amino)piperidin-1-yl)-2-(aryl)butyl)benzamides useful for the treatment of allergic diseases

Publications (2)

Publication Number	Publication Date
IL125578A0 IL125578A0 (en)	1999-03-12
IL125578A true IL125578A (en)	2002-09-12

Family

ID=27084615

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12557897A IL125578A (en)	1996-02-21	1997-01-29	N-Methyl - N - 4 - (4 (H1 - Benzimidazole-2 - Eyal - Amino) Pipridine - 1 - Eyal) 2 - (Aryl) Butyl benzamides and pharmaceutical preparations useful for the treatment of allergic diseases

Country Status (19)

Country	Link
EP (1)	EP0888336B1 (de)
JP (1)	JP2001504798A (de)
KR (1)	KR19990087131A (de)
CN (1)	CN1115341C (de)
AR (1)	AR005896A1 (de)
AT (1)	ATE221882T1 (de)
AU (1)	AU710488B2 (de)
BR (1)	BR9707652A (de)
CA (1)	CA2247105C (de)
DE (1)	DE69714579T2 (de)
DK (1)	DK0888336T3 (de)
ES (1)	ES2176687T3 (de)
HU (1)	HUP9901030A3 (de)
IL (1)	IL125578A (de)
NO (1)	NO983830L (de)
NZ (1)	NZ330908A (de)
PT (1)	PT888336E (de)
TW (1)	TW562804B (de)
WO (1)	WO1997030989A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6194406B1 (en)	1995-12-20	2001-02-27	Aventis Pharmaceuticals Inc.	Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease
US6423704B2 (en)	1995-12-20	2002-07-23	Aventis Pharmaceuticals Inc.	Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic diseases
DE60319813T2 (de) *	2002-04-18	2009-04-23	Schering Corporation	1-(4-piperidinyl)benzimidazole als histamin h3 antagonisten
DE60309598T2 (de) *	2002-06-24	2007-09-13	Schering Corp.	Als histamin-h3-antagonisten geeignete indolderivate
GB0315203D0 (en) *	2003-06-28	2003-08-06	Celltech R&D Ltd	Chemical compounds
JP2010516731A (ja)	2007-01-24	2010-05-20	グラクソグループリミテッド	２−メトキシ−５−（５−トリフルオロメチル−テトラゾール−１−イル）−ベンジル］−（２ｓ−フェニル−ピペリジン−３ｓ−イル）−アミンを含む医薬組成物

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4219559A (en) *	1979-01-10	1980-08-26	Janssen Pharmaceutica N.V.	N-Heterocyclyl-4-piperidinamines
FR2676054B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
DK0777666T3 (da) *	1994-08-25	1999-09-27	Merrell Pharma Inc	Substituerede piperidiner anvendelige ved behandling af allergiske sygdomme

1997
- 1997-01-29 CN CN97192390A patent/CN1115341C/zh not_active Expired - Fee Related
- 1997-01-29 ES ES97905689T patent/ES2176687T3/es not_active Expired - Lifetime
- 1997-01-29 PT PT97905689T patent/PT888336E/pt unknown
- 1997-01-29 CA CA002247105A patent/CA2247105C/en not_active Expired - Fee Related
- 1997-01-29 EP EP97905689A patent/EP0888336B1/de not_active Expired - Lifetime
- 1997-01-29 KR KR1019980706522A patent/KR19990087131A/ko not_active Abandoned
- 1997-01-29 DE DE69714579T patent/DE69714579T2/de not_active Expired - Fee Related
- 1997-01-29 DK DK97905689T patent/DK0888336T3/da active
- 1997-01-29 HU HU9901030A patent/HUP9901030A3/hu unknown
- 1997-01-29 AT AT97905689T patent/ATE221882T1/de not_active IP Right Cessation
- 1997-01-29 AU AU22519/97A patent/AU710488B2/en not_active Ceased
- 1997-01-29 BR BR9707652A patent/BR9707652A/pt not_active IP Right Cessation
- 1997-01-29 JP JP53016697A patent/JP2001504798A/ja not_active Abandoned
- 1997-01-29 NZ NZ330908A patent/NZ330908A/en unknown
- 1997-01-29 IL IL12557897A patent/IL125578A/en not_active IP Right Cessation
- 1997-01-29 WO PCT/US1997/001571 patent/WO1997030989A1/en not_active Ceased
- 1997-02-18 TW TW086101887A patent/TW562804B/zh not_active IP Right Cessation
- 1997-02-19 AR ARP970100645A patent/AR005896A1/es not_active Application Discontinuation
1998
- 1998-08-20 NO NO983830A patent/NO983830L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2247105A1 (en)	1997-08-28
TW562804B (en)	2003-11-21
HUP9901030A3 (en)	2002-01-28
WO1997030989A1 (en)	1997-08-28
HK1019734A1 (en)	2000-02-25
DK0888336T3 (da)	2002-12-02
NO983830L (no)	1998-10-20
HUP9901030A2 (hu)	1999-07-28
AU710488B2 (en)	1999-09-23
CA2247105C (en)	2002-05-14
NZ330908A (en)	2001-04-27
NO983830D0 (no)	1998-08-20
PT888336E (pt)	2002-12-31
AU2251997A (en)	1997-09-10
CN1211246A (zh)	1999-03-17
DE69714579D1 (de)	2002-09-12
DE69714579T2 (de)	2003-04-10
ATE221882T1 (de)	2002-08-15
KR19990087131A (ko)	1999-12-15
CN1115341C (zh)	2003-07-23
AR005896A1 (es)	1999-07-21
JP2001504798A (ja)	2001-04-10
ES2176687T3 (es)	2002-12-01
EP0888336B1 (de)	2002-08-07
IL125578A0 (en)	1999-03-12
EP0888336A1 (de)	1999-01-07
BR9707652A (pt)	1999-07-27

Legal Events

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

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