IL125577A

IL125577A - Compounds N - methyl - N - [-4 (piperidine - 1 yl) - 2 - (aryl) butyl)] Benzamide and pharmaceutical preparations used to treat allergic diseases containing them

Compounds N - methyl - N - [-4 (piperidine - 1 yl) - 2 - (aryl) butyl)] Benzamide and pharmaceutical preparations used to treat allergic diseases containing them

Info

Publication number: IL125577A
Authority: IL; Israel
Prior art keywords: methyl; benzimidazole; carbonyl; butyl; piperidin
Prior art date: 1996-02-21

Application number

IL12557797A

Other languages

English (en)

Hebrew (he)

Other versions

IL125577A0 (en

Original Assignee

Aventis Pharma Inc

Priority date

1996-02-21

Filing date

1997-01-27

Publication date

2004-03-28

1997-01-27 Application filed by Aventis Pharma Inc filed Critical Aventis Pharma Inc

1999-03-12 Publication of IL125577A0 publication Critical patent/IL125577A0/xx

2004-03-28 Publication of IL125577A publication Critical patent/IL125577A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 17
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 title description 115
208000026935 allergic disease Diseases 0.000 title description 12
238000011282 treatment Methods 0.000 title description 8
125000003118 aryl group Chemical group 0.000 title description 4
150000003936 benzamides Chemical class 0.000 title description 4
229940054066 benzamide antipsychotics Drugs 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 286
239000001257 hydrogen Substances 0.000 claims abstract description 50
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
150000003839 salts Chemical class 0.000 claims abstract description 29
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 28
150000002431 hydrogen Chemical class 0.000 claims abstract description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 10
150000002367 halogens Chemical class 0.000 claims abstract description 10
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 4
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 315
-1 2-ethoxyethyl Chemical group 0.000 claims description 198
239000000203 mixture Substances 0.000 claims description 32
150000003254 radicals Chemical class 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 22
241000009298 Trigla lyra Species 0.000 claims description 20
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
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 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
206010047700 Vomiting Diseases 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
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 180
230000015572 biosynthetic process Effects 0.000 description 171
238000003786 synthesis reaction Methods 0.000 description 170
238000000034 method Methods 0.000 description 156
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 105
239000000243 solution Substances 0.000 description 87
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
238000006243 chemical reaction Methods 0.000 description 78
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
239000012044 organic layer Substances 0.000 description 67
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 58
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
239000011541 reaction mixture Substances 0.000 description 56
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
239000000741 silica gel Substances 0.000 description 47
229910002027 silica gel Inorganic materials 0.000 description 47
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 46
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
235000008504 concentrate Nutrition 0.000 description 44
239000012141 concentrate Substances 0.000 description 44
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
229920006395 saturated elastomer Polymers 0.000 description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
238000002360 preparation method Methods 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
102000003141 Tachykinin Human genes 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
108060008037 tachykinin Proteins 0.000 description 27
239000012267 brine Substances 0.000 description 25
238000010992 reflux Methods 0.000 description 25
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
235000017557 sodium bicarbonate Nutrition 0.000 description 22
229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
239000002904 solvent Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
239000005557 antagonist Substances 0.000 description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 20
229960001340 histamine Drugs 0.000 description 20
239000010410 layer Substances 0.000 description 20
201000010099 disease Diseases 0.000 description 19
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
239000007864 aqueous solution Substances 0.000 description 18
239000012467 final product Substances 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
239000011780 sodium chloride 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
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
238000001704 evaporation Methods 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
239000000047 product Substances 0.000 description 16
108020003175 receptors Proteins 0.000 description 16
102100024304 Protachykinin-1 Human genes 0.000 description 15
101800003906 Substance P Proteins 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
230000008485 antagonism Effects 0.000 description 15
239000002585 base Substances 0.000 description 15
238000004587 chromatography analysis Methods 0.000 description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
238000000605 extraction Methods 0.000 description 15
102000005962 receptors Human genes 0.000 description 15
238000003756 stirring Methods 0.000 description 15
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
230000004044 response Effects 0.000 description 14
239000007787 solid Substances 0.000 description 14
238000001665 trituration Methods 0.000 description 14
239000012359 Methanesulfonyl chloride Substances 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 13
238000001953 recrystallisation Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 11
206010020751 Hypersensitivity Diseases 0.000 description 11
230000027455 binding Effects 0.000 description 11
235000011089 carbon dioxide Nutrition 0.000 description 11
238000001035 drying Methods 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000000872 buffer Substances 0.000 description 10
238000010511 deprotection reaction Methods 0.000 description 10
239000007789 gas Substances 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
239000012312 sodium hydride Substances 0.000 description 10
229910000104 sodium hydride Inorganic materials 0.000 description 10
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
235000019270 ammonium chloride Nutrition 0.000 description 9
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 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
238000005192 partition Methods 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
235000011121 sodium hydroxide Nutrition 0.000 description 9
238000012360 testing method Methods 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 8
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 8
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 8
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
208000024780 Urticaria Diseases 0.000 description 8
238000001914 filtration Methods 0.000 description 8
235000011181 potassium carbonates Nutrition 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
239000012047 saturated solution Substances 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
230000007815 allergy Effects 0.000 description 7
239000000975 dye Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000002464 receptor antagonist Substances 0.000 description 7
229940044551 receptor antagonist Drugs 0.000 description 7
229910000029 sodium carbonate Inorganic materials 0.000 description 7
235000017550 sodium carbonate Nutrition 0.000 description 7
206010049153 Allergic sinusitis Diseases 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
101100406879 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) par-2 gene Proteins 0.000 description 6
208000036284 Rhinitis seasonal Diseases 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
201000008937 atopic dermatitis Diseases 0.000 description 6
208000010668 atopic eczema Diseases 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
229960004424 carbon dioxide Drugs 0.000 description 6
XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 6
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
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 6
XVUPBAZUNVHLSL-UHFFFAOYSA-N n-methyl-n-(4-methylsulfonyl-2-phenylbutyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(CCS(C)(=O)=O)C1=CC=CC=C1 XVUPBAZUNVHLSL-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
QHUONPBMMFBIQD-UHFFFAOYSA-N 1h-benzimidazol-2-yl(piperidin-4-yl)methanone;hydroiodide Chemical compound I.N=1C2=CC=CC=C2NC=1C(=O)C1CCNCC1 QHUONPBMMFBIQD-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
238000004458 analytical method Methods 0.000 description 5
125000001246 bromo group Chemical group Br* 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
239000007858 starting material Substances 0.000 description 5
GPTVQTPMFOLLOA-UHFFFAOYSA-N 1-chloro-2-ethoxyethane Chemical compound CCOCCCl GPTVQTPMFOLLOA-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
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
241000700199 Cavia porcellus Species 0.000 description 4
206010009900 Colitis ulcerative Diseases 0.000 description 4
208000011231 Crohn disease Diseases 0.000 description 4
206010012438 Dermatitis atopic Diseases 0.000 description 4
206010012442 Dermatitis contact Diseases 0.000 description 4
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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
201000006704 Ulcerative Colitis Diseases 0.000 description 4
PFRRRXFREJFWAK-UHFFFAOYSA-N [1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-piperidin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCNCC1 PFRRRXFREJFWAK-UHFFFAOYSA-N 0.000 description 4
238000009825 accumulation Methods 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
239000000739 antihistaminic agent Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
239000001045 blue dye Substances 0.000 description 4
229940098773 bovine serum albumin Drugs 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
230000002860 competitive effect Effects 0.000 description 4
208000010247 contact dermatitis Diseases 0.000 description 4
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
210000003405 ileum Anatomy 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
229960000367 inositol Drugs 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
PSCXCIPPRCFAAO-UHFFFAOYSA-N methyl 5-amino-2-methoxybenzoate Chemical compound COC(=O)C1=CC(N)=CC=C1OC PSCXCIPPRCFAAO-UHFFFAOYSA-N 0.000 description 4
FYXYFJUZTYJVQO-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-methylsulfonylbutyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(CCS(C)(=O)=O)C1=CC=C(Cl)C(Cl)=C1 FYXYFJUZTYJVQO-UHFFFAOYSA-N 0.000 description 4
239000008188 pellet Substances 0.000 description 4
QVWLRRNBENTDIQ-UHFFFAOYSA-N piperidin-4-yl-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]methanone;hydroiodide Chemical compound I.N=1C2=CC=CC=C2N(CC=2N=CC=CC=2)C=1C(=O)C1CCNCC1 QVWLRRNBENTDIQ-UHFFFAOYSA-N 0.000 description 4
150000003053 piperidines Chemical class 0.000 description 4
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 4
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
239000000843 powder Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
210000003437 trachea Anatomy 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 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical group OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
108010072901 Tachykinin Receptors Proteins 0.000 description 3
102000007124 Tachykinin Receptors Human genes 0.000 description 3
GGNMTJKRHHLJHH-UHFFFAOYSA-N Trimethylaethergallussaeure-amid Natural products COC1=CC(C(N)=O)=CC(OC)=C1OC GGNMTJKRHHLJHH-UHFFFAOYSA-N 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
206010006451 bronchitis Diseases 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
GFHNAMRJFCEERV-UHFFFAOYSA-L cobalt chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Co+2] GFHNAMRJFCEERV-UHFFFAOYSA-L 0.000 description 3
239000012153 distilled water Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical class OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
DPWUYLYWKUUALE-UHFFFAOYSA-N methyl 2-methoxy-5-(4h-triazol-4-yl)benzoate Chemical compound C1=C(OC)C(C(=O)OC)=CC(C2N=NN=C2)=C1 DPWUYLYWKUUALE-UHFFFAOYSA-N 0.000 description 3
239000012022 methylating agents‎ Substances 0.000 description 3
CEPJHPSOCMJKSA-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-methylsulfonylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 CEPJHPSOCMJKSA-UHFFFAOYSA-N 0.000 description 3
210000005036 nerve Anatomy 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
239000003921 oil Substances 0.000 description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
235000021317 phosphate Nutrition 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000011736 potassium bicarbonate Substances 0.000 description 3
235000015497 potassium bicarbonate Nutrition 0.000 description 3
229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
ASHGTUMKRVIOLH-UHFFFAOYSA-L potassium;sodium;hydrogen phosphate Chemical compound [Na+].[K+].OP([O-])([O-])=O ASHGTUMKRVIOLH-UHFFFAOYSA-L 0.000 description 3
125000004076 pyridyl group Chemical class 0.000 description 3
206010039083 rhinitis Diseases 0.000 description 3
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 3
230000001953 sensory effect Effects 0.000 description 3
210000003491 skin Anatomy 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
230000009870 specific binding Effects 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
238000012546 transfer Methods 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 2
RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 2
DSLRVRBSNLHVBH-UHFFFAOYSA-N 2,5-furandimethanol Chemical compound OCC1=CC=C(CO)O1 DSLRVRBSNLHVBH-UHFFFAOYSA-N 0.000 description 2
HRBLSBRWIWIOGW-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxy)ethanol Chemical compound OCCOCC(F)(F)F HRBLSBRWIWIOGW-UHFFFAOYSA-N 0.000 description 2
SGVWGQRMFAWWKV-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-(oxan-2-yloxy)butan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CN)CCOC1CCCCO1 SGVWGQRMFAWWKV-UHFFFAOYSA-N 0.000 description 2
DAMRCQIFNHBTOR-UHFFFAOYSA-N 2-(furan-2-ylmethoxy)ethanol Chemical compound OCCOCC1=CC=CO1 DAMRCQIFNHBTOR-UHFFFAOYSA-N 0.000 description 2
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 2
QDQKCZDJPIUHNS-UHFFFAOYSA-N 2-methoxy-5-(4h-triazol-4-yl)benzoyl chloride Chemical compound C1=C(C(Cl)=O)C(OC)=CC=C1C1N=NN=C1 QDQKCZDJPIUHNS-UHFFFAOYSA-N 0.000 description 2
HURBWIHJHDFCGU-UHFFFAOYSA-N 2-methoxy-5-(trifluoromethoxy)benzoic acid Chemical compound COC1=CC=C(OC(F)(F)F)C=C1C(O)=O HURBWIHJHDFCGU-UHFFFAOYSA-N 0.000 description 2
RUAKPPHFBCDTSH-UHFFFAOYSA-N 2-methoxy-5-(trifluoromethoxy)benzoyl chloride Chemical compound COC1=CC=C(OC(F)(F)F)C=C1C(Cl)=O RUAKPPHFBCDTSH-UHFFFAOYSA-N 0.000 description 2
PXKUSFRFMCCLJI-UHFFFAOYSA-N 3,4,5-trimethoxy-n-methyl-n-[4-methylsulfonyl-2-[3-(trifluoromethyl)phenyl]butyl]benzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 PXKUSFRFMCCLJI-UHFFFAOYSA-N 0.000 description 2
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
SCYRKKLGMZNVKK-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-(4-fluorophenyl)butan-1-amine Chemical compound CC(C)(C)[Si](C)(C)OCCC(CN)C1=CC=C(F)C=C1 SCYRKKLGMZNVKK-UHFFFAOYSA-N 0.000 description 2
VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical class O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 2
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 description 2
208000028185 Angioedema Diseases 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
108010001478 Bacitracin Proteins 0.000 description 2
108010017384 Blood Proteins Proteins 0.000 description 2
102000004506 Blood Proteins Human genes 0.000 description 2
241000700198 Cavia Species 0.000 description 2
OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
206010012434 Dermatitis allergic Diseases 0.000 description 2
206010012735 Diarrhoea Diseases 0.000 description 2
206010015866 Extravasation Diseases 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
102000000543 Histamine Receptors Human genes 0.000 description 2
108010002059 Histamine Receptors Proteins 0.000 description 2
241000282412 Homo Species 0.000 description 2
208000001718 Immediate Hypersensitivity Diseases 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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 2
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
208000019693 Lung disease Diseases 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
206010028748 Nasal obstruction Diseases 0.000 description 2
206010028813 Nausea Diseases 0.000 description 2
101800000399 Neurokinin A Proteins 0.000 description 2
HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 2
102400000097 Neurokinin A Human genes 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
229920002873 Polyethylenimine Polymers 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
108010036928 Thiorphan Proteins 0.000 description 2
206010045240 Type I hypersensitivity Diseases 0.000 description 2
INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 2
JJZPWCVHSLZLQC-UHFFFAOYSA-N [N].C1=CC=C2NC=NC2=C1 Chemical compound [N].C1=CC=C2NC=NC2=C1 JJZPWCVHSLZLQC-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
230000002411 adverse Effects 0.000 description 2
229910000272 alkali metal oxide Inorganic materials 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
230000000172 allergic effect Effects 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
208000010216 atopic IgE responsiveness Diseases 0.000 description 2
229960003071 bacitracin Drugs 0.000 description 2
229930184125 bacitracin Natural products 0.000 description 2
CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical class C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
MAPRDOKILZKGDP-UHFFFAOYSA-N bromo-chloro-iodomethanesulfonic acid Chemical compound OS(=O)(=O)C(Cl)(Br)I MAPRDOKILZKGDP-UHFFFAOYSA-N 0.000 description 2
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
210000000621 bronchi Anatomy 0.000 description 2
YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
108010086192 chymostatin Proteins 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
230000036251 extravasation Effects 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
235000013305 food Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
201000005298 gastrointestinal allergy Diseases 0.000 description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
230000008105 immune reaction Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 2
125000002346 iodo group Chemical group I* 0.000 description 2
239000002085 irritant Substances 0.000 description 2
231100000021 irritant Toxicity 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000008101 lactose Substances 0.000 description 2
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
108010052968 leupeptin Proteins 0.000 description 2
238000012417 linear regression Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000008018 melting Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 2
DOBFJVVTBNTGCW-UHFFFAOYSA-N methyl 2-methoxy-5-nitrobenzoate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC=C1OC DOBFJVVTBNTGCW-UHFFFAOYSA-N 0.000 description 2
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
CNJKUJVPKMEXQZ-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-methylsulfonylbutyl]-2-methoxy-n-methyl-5-(trifluoromethoxy)benzamide Chemical compound COC1=CC=C(OC(F)(F)F)C=C1C(=O)N(C)CC(CCS(C)(=O)=O)C1=CC=C(Cl)C(Cl)=C1 CNJKUJVPKMEXQZ-UHFFFAOYSA-N 0.000 description 2
UCUFNUDOCAGGNI-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)-4-methylsulfonylbutyl]-n-methylbenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CCS(C)(=O)=O)CN(C)C(=O)C1=CC=CC=C1 UCUFNUDOCAGGNI-UHFFFAOYSA-N 0.000 description 2
ABDBEDHQIPLFGK-UHFFFAOYSA-N n-[2-(3,4-dimethylphenyl)-4-methylsulfonylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=C(C)C(C)=CC=2)=C1 ABDBEDHQIPLFGK-UHFFFAOYSA-N 0.000 description 2
KHMNTVZPVHJAPQ-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-hydroxybutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCO)C=2C=C(Cl)C=CC=2)=C1 KHMNTVZPVHJAPQ-UHFFFAOYSA-N 0.000 description 2
SDKIFVJEDAIVHX-UHFFFAOYSA-N n-[2-(4-chlorophenyl)-4-methylsulfonylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=CC(Cl)=CC=2)=C1 SDKIFVJEDAIVHX-UHFFFAOYSA-N 0.000 description 2
TYUMPRJRGVJWLU-UHFFFAOYSA-N n-[4-[4-(1h-benzimidazole-2-carbonyl)piperidin-1-yl]-2-(3,4-dichlorophenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2NC3=CC=CC=C3N=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 TYUMPRJRGVJWLU-UHFFFAOYSA-N 0.000 description 2
WDUUTGSVXMPUQN-UHFFFAOYSA-N n-[4-[4-(1h-benzimidazole-2-carbonyl)piperidin-1-yl]-2-(3,4-dichlorophenyl)butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(CCN1CCC(CC1)C(=O)C=1NC2=CC=CC=C2N=1)C1=CC=C(Cl)C(Cl)=C1 WDUUTGSVXMPUQN-UHFFFAOYSA-N 0.000 description 2
NPYIVQCGBJTCMA-UHFFFAOYSA-N n-[4-[4-(1h-benzimidazole-2-carbonyl)piperidin-1-yl]-2-(3-chlorophenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2NC3=CC=CC=C3N=2)C=2C=C(Cl)C=CC=2)=C1 NPYIVQCGBJTCMA-UHFFFAOYSA-N 0.000 description 2
XRZRFGQZSVXSLC-UHFFFAOYSA-N n-[4-hydroxy-2-[3-(trifluoromethyl)phenyl]butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCO)C=2C=C(C=CC=2)C(F)(F)F)=C1 XRZRFGQZSVXSLC-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
230000008693 nausea Effects 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
230000010412 perfusion Effects 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
150000003905 phosphatidylinositols Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
229910003446 platinum oxide Inorganic materials 0.000 description 2
229940068917 polyethylene glycols Drugs 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
230000004224 protection Effects 0.000 description 2
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000006188 syrup Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
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 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
230000007306 turnover Effects 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
HQSXXOOVLCEFBK-UHFFFAOYSA-N 1,3-benzothiazol-2-yl(piperidin-4-yl)methanone Chemical compound N=1C2=CC=CC=C2SC=1C(=O)C1CCNCC1 HQSXXOOVLCEFBK-UHFFFAOYSA-N 0.000 description 1
JBJUUEWWQLMAJH-UHFFFAOYSA-N 1-(2-ethoxyethyl)benzimidazole Chemical compound C1=CC=C2N(CCOCC)C=NC2=C1 JBJUUEWWQLMAJH-UHFFFAOYSA-N 0.000 description 1
JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 1
NOAFZIOGGDPYKK-UHFFFAOYSA-N 1-methoxy-4-(trifluoromethoxy)benzene Chemical compound COC1=CC=C(OC(F)(F)F)C=C1 NOAFZIOGGDPYKK-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
AAUXWIRWTKPURY-UHFFFAOYSA-N 1h-benzimidazol-2-yl(piperidin-4-yl)methanone Chemical compound N=1C2=CC=CC=C2NC=1C(=O)C1CCNCC1 AAUXWIRWTKPURY-UHFFFAOYSA-N 0.000 description 1
PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
ZGBPYNDDFVNFOT-UHFFFAOYSA-N 2-(2-but-2-enoxyethoxy)oxane Chemical compound CC=CCOCCOC1CCCCO1 ZGBPYNDDFVNFOT-UHFFFAOYSA-N 0.000 description 1
QKSKKRXPQXKKIJ-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-(oxan-2-yloxy)butanenitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C#N)CCOC1OCCCC1 QKSKKRXPQXKKIJ-UHFFFAOYSA-N 0.000 description 1
QWZNCAFWRZZJMA-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1Cl QWZNCAFWRZZJMA-UHFFFAOYSA-N 0.000 description 1
ASLSUMISAQDOOB-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C=C1OC ASLSUMISAQDOOB-UHFFFAOYSA-N 0.000 description 1
XNSHCUIBMZSUGL-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)acetonitrile Chemical compound CC1=CC=C(CC#N)C=C1C XNSHCUIBMZSUGL-UHFFFAOYSA-N 0.000 description 1
PACGLQCRGWFBJH-UHFFFAOYSA-N 2-(4-methoxyphenyl)acetonitrile Chemical compound COC1=CC=C(CC#N)C=C1 PACGLQCRGWFBJH-UHFFFAOYSA-N 0.000 description 1
BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
HMRDNLZZHLHXLP-UHFFFAOYSA-N 2-[2-(2,2,2-trifluoroethoxy)ethoxy]oxane Chemical compound FC(F)(F)COCCOC1CCCCO1 HMRDNLZZHLHXLP-UHFFFAOYSA-N 0.000 description 1
JOIYKSLWXLFGGR-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetonitrile Chemical compound FC(F)(F)C1=CC=CC(CC#N)=C1 JOIYKSLWXLFGGR-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
QSECPQCFCWVBKM-UHFFFAOYSA-N 2-iodoethanol Chemical compound OCCI QSECPQCFCWVBKM-UHFFFAOYSA-N 0.000 description 1
UQMAWQAAKUZBHQ-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1N1N=NN=C1 UQMAWQAAKUZBHQ-UHFFFAOYSA-N 0.000 description 1
ATRDCTRZAJKDPL-UHFFFAOYSA-N 2-methoxy-5-(trifluoromethoxy)benzaldehyde Chemical compound COC1=CC=C(OC(F)(F)F)C=C1C=O ATRDCTRZAJKDPL-UHFFFAOYSA-N 0.000 description 1
MNWSGMTUGXNYHJ-UHFFFAOYSA-N 2-methoxybenzamide Chemical compound COC1=CC=CC=C1C(N)=O MNWSGMTUGXNYHJ-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
LPCWDVLDJVZIHA-UHFFFAOYSA-N 2-naphthalen-2-ylacetonitrile Chemical compound C1=CC=CC2=CC(CC#N)=CC=C21 LPCWDVLDJVZIHA-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
GCYHRYNSUGLLMA-UHFFFAOYSA-N 2-prop-2-enoxyethanol Chemical compound OCCOCC=C GCYHRYNSUGLLMA-UHFFFAOYSA-N 0.000 description 1
OIPHWUPMXHQWLR-UHFFFAOYSA-N 2-pyridin-3-ylacetonitrile Chemical compound N#CCC1=CC=CN=C1 OIPHWUPMXHQWLR-UHFFFAOYSA-N 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
CLSHQIDDCJTHAJ-UHFFFAOYSA-N 2-thienylacetonitrile Chemical compound N#CCC1=CC=CS1 CLSHQIDDCJTHAJ-UHFFFAOYSA-N 0.000 description 1
ZLFCYITUTWWEPJ-UHFFFAOYSA-N 3,4,5-trimethoxy-n-[2-(3-methoxyphenyl)-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound COC1=CC=CC(C(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2N=CC=CC=2)CN(C)C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)=C1 ZLFCYITUTWWEPJ-UHFFFAOYSA-N 0.000 description 1
UEXPIEIHYNJPMT-UHFFFAOYSA-N 3,4,5-trimethoxy-n-[2-(4-methoxyphenyl)-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(CN(C)C(=O)C=1C=C(OC)C(OC)=C(OC)C=1)CCN1CCC(C(=O)C=2N(C3=CC=CC=C3N=2)CC=2N=CC=CC=2)CC1 UEXPIEIHYNJPMT-UHFFFAOYSA-N 0.000 description 1
MVUYZDSJLVETKB-UHFFFAOYSA-N 3,4,5-trimethoxy-n-methyl-n-[4-[4-[1-(2-oxopropyl)benzimidazole-2-carbonyl]piperidin-1-yl]-2-phenylbutyl]benzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC(C)=O)C=2C=CC=CC=2)=C1 MVUYZDSJLVETKB-UHFFFAOYSA-N 0.000 description 1
CSEIBMYBZLGKRN-UHFFFAOYSA-N 3-(2-methylsulfonylethoxy)prop-1-ene Chemical compound CS(=O)(=O)CCOCC=C CSEIBMYBZLGKRN-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
MSQUNDKURWEVPP-UHFFFAOYSA-N 4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]piperidin-4-ol Chemical compound N=1C2=CC=CC=C2N(CC=2C=CC(F)=CC=2)C=1C1(O)CCNCC1 MSQUNDKURWEVPP-UHFFFAOYSA-N 0.000 description 1
YAMVEABATZOFEK-UHFFFAOYSA-N 4-[3-[2-[1-[3-(3-chlorophenyl)-4-[methyl-(3,4,5-trimethoxybenzoyl)amino]butyl]piperidine-4-carbonyl]benzimidazol-1-yl]propyl]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CCCC=2C=CC(=CC=2)C(O)=O)C=2C=C(Cl)C=CC=2)=C1 YAMVEABATZOFEK-UHFFFAOYSA-N 0.000 description 1
QMNNQRJBJZAPSG-UHFFFAOYSA-N 4-[[2-[1-[3-(3,4-dichlorophenyl)-4-[methyl-(3,4,5-trimethoxybenzoyl)amino]butyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2C=CC(=CC=2)C(O)=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 QMNNQRJBJZAPSG-UHFFFAOYSA-N 0.000 description 1
SWNRZAKWGNRJOM-UHFFFAOYSA-N 4-[[2-[1-[4-[benzoyl(methyl)amino]-3-phenylbutyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoic acid Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=C(C(O)=O)C=C1 SWNRZAKWGNRJOM-UHFFFAOYSA-N 0.000 description 1
GQOYUKHGMCCVMY-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-(4-chlorophenyl)butan-1-amine Chemical compound CC(C)(C)[Si](C)(C)OCCC(CN)C1=CC=C(Cl)C=C1 GQOYUKHGMCCVMY-UHFFFAOYSA-N 0.000 description 1
HUWYFNLIPQXJBB-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-(4-chlorophenyl)butanenitrile Chemical compound CC(C)(C)[Si](C)(C)OCCC(C#N)C1=CC=C(Cl)C=C1 HUWYFNLIPQXJBB-UHFFFAOYSA-N 0.000 description 1
UXHCPBLMINSNRY-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-(4-methoxyphenyl)butanenitrile Chemical compound COC1=CC=C(C(CCO[Si](C)(C)C(C)(C)C)C#N)C=C1 UXHCPBLMINSNRY-UHFFFAOYSA-N 0.000 description 1
VZGIQCDZAHUHSJ-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-pyridin-3-ylbutan-1-amine Chemical compound CC(C)(C)[Si](C)(C)OCCC(CN)C1=CC=CN=C1 VZGIQCDZAHUHSJ-UHFFFAOYSA-N 0.000 description 1
XXVSIRNSFPICII-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-pyridin-3-ylbutanenitrile Chemical compound CC(C)(C)[Si](C)(C)OCCC(C#N)C1=CC=CN=C1 XXVSIRNSFPICII-UHFFFAOYSA-N 0.000 description 1
WOWUBANSYOYKPQ-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxy-2-thiophen-2-ylbutanenitrile Chemical compound CC(C)(C)[Si](C)(C)OCCC(C#N)C1=CC=CS1 WOWUBANSYOYKPQ-UHFFFAOYSA-N 0.000 description 1
IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 description 1
CMNQIVHHHBBVSC-UHFFFAOYSA-N 5-hydroxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound O=C1NCCC2=C1C=CC=C2O CMNQIVHHHBBVSC-UHFFFAOYSA-N 0.000 description 1
PPDRLQLKHRZIJC-UHFFFAOYSA-N 5-nitrosalicylic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1O PPDRLQLKHRZIJC-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
206010003497 Asphyxia Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BYYMILHAKOURNM-UHFFFAOYSA-N Buturon Chemical compound C#CC(C)N(C)C(=O)NC1=CC=C(Cl)C=C1 BYYMILHAKOURNM-UHFFFAOYSA-N 0.000 description 1
COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
RDMPZFBRUAADII-UHFFFAOYSA-N CN(C(C1=CC(=C(C(=C1)OC)OC)OC)=O)CC(CCO)C1=C(C=CC=C1)Cl Chemical compound CN(C(C1=CC(=C(C(=C1)OC)OC)OC)=O)CC(CCO)C1=C(C=CC=C1)Cl RDMPZFBRUAADII-UHFFFAOYSA-N 0.000 description 1
101100455752 Caenorhabditis elegans lys-3 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
244000025254 Cannabis sativa Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
238000005967 Finkelstein reaction Methods 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229910021380 Manganese Chloride Inorganic materials 0.000 description 1
GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010028735 Nasal congestion Diseases 0.000 description 1
102000046798 Neurokinin B Human genes 0.000 description 1
NHXYSAFTNPANFK-HDMCBQFHSA-N Neurokinin B Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O)C1=CC=CC=C1 NHXYSAFTNPANFK-HDMCBQFHSA-N 0.000 description 1
108010040722 Neurokinin-2 Receptors Proteins 0.000 description 1
101800002813 Neurokinin-B Proteins 0.000 description 1
102100029409 Neuromedin-K receptor Human genes 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
241001494479 Pecora Species 0.000 description 1
239000004264 Petrolatum Substances 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
208000036071 Rhinorrhea Diseases 0.000 description 1
206010039101 Rhinorrhoea Diseases 0.000 description 1
238000003436 Schotten-Baumann reaction Methods 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
239000004280 Sodium formate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
102100037342 Substance-K receptor Human genes 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
JBYTWVLKQDNDMN-UHFFFAOYSA-N [1-(furan-2-ylmethyl)benzimidazol-2-yl]-piperidin-4-ylmethanone Chemical compound N=1C2=CC=CC=C2N(CC=2OC=CC=2)C=1C(=O)C1CCNCC1 JBYTWVLKQDNDMN-UHFFFAOYSA-N 0.000 description 1
RSAJQPZSDUXGSN-UHFFFAOYSA-N [1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-piperidin-4-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCNCC1 RSAJQPZSDUXGSN-UHFFFAOYSA-N 0.000 description 1
NSRGCYQRQJUNDB-UHFFFAOYSA-N [1-[2-(furan-2-ylmethoxy)ethyl]benzimidazol-2-yl]-piperidin-4-ylmethanone Chemical compound N=1C2=CC=CC=C2N(CCOCC=2OC=CC=2)C=1C(=O)C1CCNCC1 NSRGCYQRQJUNDB-UHFFFAOYSA-N 0.000 description 1
YJZYLULSXLDIAW-UHFFFAOYSA-N [5-[[tert-butyl(dimethyl)silyl]oxymethyl]furan-2-yl]methanol Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=C(CO)O1 YJZYLULSXLDIAW-UHFFFAOYSA-N 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
239000013566 allergen Substances 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000003708 ampul Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000005875 antibody response Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000003975 aryl alkyl amines Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical class [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical compound Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 1
CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 description 1
KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910021538 borax Inorganic materials 0.000 description 1
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
235000017663 capsaicin Nutrition 0.000 description 1
229960002504 capsaicin Drugs 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
235000015218 chewing gum Nutrition 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
230000012085 chronic inflammatory response Effects 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000000576 coating method Methods 0.000 description 1
GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000004590 computer program Methods 0.000 description 1
229940124301 concurrent medication Drugs 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
AJFXNBUVIBKWBT-UHFFFAOYSA-N disodium;boric acid;hydrogen borate Chemical compound [Na+].[Na+].OB(O)O.OB(O)O.OB(O)O.OB([O-])[O-] AJFXNBUVIBKWBT-UHFFFAOYSA-N 0.000 description 1
229960001484 edetic acid Drugs 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
PVPZCALMRUZDQW-UHFFFAOYSA-N ethyl 2-(furan-2-ylmethoxy)acetate Chemical compound CCOC(=O)COCC1=CC=CO1 PVPZCALMRUZDQW-UHFFFAOYSA-N 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
229960003699 evans blue Drugs 0.000 description 1
238000013401 experimental design Methods 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000010575 fractional recrystallization Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000000762 glandular Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000011597 hartley guinea pig Methods 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
230000036541 health Effects 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
230000004047 hyperresponsiveness Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
210000004969 inflammatory cell Anatomy 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
230000005722 itchiness Effects 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
235000019388 lanolin Nutrition 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 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
239000011777 magnesium Substances 0.000 description 1
OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
229910001623 magnesium bromide Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000011565 manganese chloride Substances 0.000 description 1
235000002867 manganese chloride Nutrition 0.000 description 1
229940099607 manganese chloride Drugs 0.000 description 1
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
229960000582 mepyramine Drugs 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
YDWPOGYTJVQQIL-UHFFFAOYSA-N methyl 2-(4-aminophenoxy)acetate Chemical compound COC(=O)COC1=CC=C(N)C=C1 YDWPOGYTJVQQIL-UHFFFAOYSA-N 0.000 description 1
NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
KYIBQZDURAZVSM-UHFFFAOYSA-N methyl 4-[[2-[1-[4-[benzoyl(methyl)amino]-3-(3,4-dichlorophenyl)butyl]piperidine-4-carbonyl]benzimidazol-1-yl]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C2=CC=CC=C2N=C1C(=O)C1CCN(CCC(CN(C)C(=O)C=2C=CC=CC=2)C=2C=C(Cl)C(Cl)=CC=2)CC1 KYIBQZDURAZVSM-UHFFFAOYSA-N 0.000 description 1
STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
229940012189 methyl orange Drugs 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
238000003801 milling Methods 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000006011 modification reaction Methods 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
UQWQKBYIUOHMCI-UHFFFAOYSA-N n-(4-hydroxy-2-naphthalen-2-ylbutyl)-n-methylbenzamide Chemical compound C=1C=C2C=CC=CC2=CC=1C(CCO)CN(C)C(=O)C1=CC=CC=C1 UQWQKBYIUOHMCI-UHFFFAOYSA-N 0.000 description 1
RIOWUBGGFFLRNZ-UHFFFAOYSA-N n-(4-hydroxy-2-pyridin-3-ylbutyl)-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCO)C=2C=NC=CC=2)=C1 RIOWUBGGFFLRNZ-UHFFFAOYSA-N 0.000 description 1
FVRIWJLDQFJTSO-UHFFFAOYSA-N n-[2-(1,3-benzodioxol-5-yl)-4-methylsulfonylbutyl]-n-methylbenzamide Chemical compound C=1C=C2OCOC2=CC=1C(CCS(C)(=O)=O)CN(C)C(=O)C1=CC=CC=C1 FVRIWJLDQFJTSO-UHFFFAOYSA-N 0.000 description 1
KPNZNOAZXBYQQE-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-(oxan-2-yloxy)butyl]benzamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(CNC(=O)C=1C=CC=CC=1)CCOC1OCCCC1 KPNZNOAZXBYQQE-UHFFFAOYSA-N 0.000 description 1
SBHSULZPZSAAED-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-[4-[1-(furan-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=C(Cl)C(Cl)=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=CO1 SBHSULZPZSAAED-UHFFFAOYSA-N 0.000 description 1
GJANBPRRLUJVHU-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-[4-[1-[[5-(hydroxymethyl)furan-2-yl]methyl]benzimidazole-2-carbonyl]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)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2OC(CO)=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 GJANBPRRLUJVHU-UHFFFAOYSA-N 0.000 description 1
XNGHXOQPEJRBSW-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]-2-methoxy-n-methyl-5-(trifluoromethoxy)benzamide Chemical compound COC1=CC=C(OC(F)(F)F)C=C1C(=O)N(C)CC(CCO)C1=CC=C(Cl)C(Cl)=C1 XNGHXOQPEJRBSW-UHFFFAOYSA-N 0.000 description 1
YJEUQLNHCSHDAQ-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-hydroxybutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCO)C=2C=C(Cl)C(Cl)=CC=2)=C1 YJEUQLNHCSHDAQ-UHFFFAOYSA-N 0.000 description 1
RRHHIBPCTALITH-UHFFFAOYSA-N n-[2-(3,4-dichlorophenyl)-4-methylsulfonylbutyl]-n-methyl-3,5-bis(trifluoromethyl)benzamide Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(=O)N(C)CC(CCS(C)(=O)=O)C1=CC=C(Cl)C(Cl)=C1 RRHHIBPCTALITH-UHFFFAOYSA-N 0.000 description 1
BCRGZQUDTWWGIG-UHFFFAOYSA-N n-[2-(3,4-difluorophenyl)-4-[4-[1-(furan-2-ylmethyl)benzimidazole-2-carbonyl]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)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2OC=CC=2)C=2C=C(F)C(F)=CC=2)=C1 BCRGZQUDTWWGIG-UHFFFAOYSA-N 0.000 description 1
PZEUPOUTKNLJNN-UHFFFAOYSA-N n-[2-(3,4-difluorophenyl)-4-[4-[1-(furan-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=C(F)C(F)=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=CO1 PZEUPOUTKNLJNN-UHFFFAOYSA-N 0.000 description 1
SBYMZGLVGFBGPF-UHFFFAOYSA-N n-[2-(3,4-difluorophenyl)-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=C(F)C(F)=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=CC=N1 SBYMZGLVGFBGPF-UHFFFAOYSA-N 0.000 description 1
YINUUXMVIQEVIP-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)-4-[4-[1-(2-ethoxyethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C=1C=C(OC)C(OC)=CC=1)CN(C)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 YINUUXMVIQEVIP-UHFFFAOYSA-N 0.000 description 1
SJQCPRAVZQQQPL-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)-4-[4-[1-(2-ethoxyethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C=1C=C(OC)C(OC)=CC=1)CN(C)C(=O)C1=CC=CC=C1 SJQCPRAVZQQQPL-UHFFFAOYSA-N 0.000 description 1
WDKDIMMEGJUAFA-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)-4-[4-[1-(furan-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(CN(C)C(=O)C=1C=C(OC)C(OC)=C(OC)C=1)CCN1CCC(C(=O)C=2N(C3=CC=CC=C3N=2)CC=2OC=CC=2)CC1 WDKDIMMEGJUAFA-UHFFFAOYSA-N 0.000 description 1
ANXWPGPLJAGAHH-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-[4-[1-(2-oxopropyl)benzimidazole-2-carbonyl]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)C(=O)C=2N(C3=CC=CC=C3N=2)CC(C)=O)C=2C=C(Cl)C=CC=2)=C1 ANXWPGPLJAGAHH-UHFFFAOYSA-N 0.000 description 1
XQGQQRYEUHINGA-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-[4-[1-(furan-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=C(Cl)C=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=CO1 XQGQQRYEUHINGA-UHFFFAOYSA-N 0.000 description 1
YHJUIRAOLUAIBN-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]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)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2N=CC=CC=2)C=2C=C(Cl)C=CC=2)=C1 YHJUIRAOLUAIBN-UHFFFAOYSA-N 0.000 description 1
FVLDUXCQKADULA-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-[4-[1-[(5-methylfuran-2-yl)methyl]benzimidazole-2-carbonyl]piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=C(Cl)C=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=C(C)O1 FVLDUXCQKADULA-UHFFFAOYSA-N 0.000 description 1
YFFFTTYPWHWLMN-UHFFFAOYSA-N n-[2-(3-chlorophenyl)-4-methylsulfonylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=C(Cl)C=CC=2)=C1 YFFFTTYPWHWLMN-UHFFFAOYSA-N 0.000 description 1
JBKAYBBMRITFMU-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]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)C(=O)C=2N(C3=CC=CC=C3N=2)CC=2N=CC=CC=2)C=2C=CC(F)=CC=2)=C1 JBKAYBBMRITFMU-UHFFFAOYSA-N 0.000 description 1
RBRZJIKDQCMICP-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-hydroxybutyl]-2-methoxy-n-methyl-5-(tetrazol-1-yl)benzamide Chemical compound COC1=CC=C(N2N=NN=C2)C=C1C(=O)N(C)CC(CCO)C1=CC=C(F)C=C1 RBRZJIKDQCMICP-UHFFFAOYSA-N 0.000 description 1
NQBZPNMQRDOLHX-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-methylsulfonylbutyl]-2-methoxy-n-methyl-5-(4h-triazol-4-yl)benzamide Chemical compound COC1=CC=C(C2N=NN=C2)C=C1C(=O)N(C)CC(CCS(C)(=O)=O)C1=CC=C(F)C=C1 NQBZPNMQRDOLHX-UHFFFAOYSA-N 0.000 description 1
KWAIIOSCYWCVPV-UHFFFAOYSA-N n-[2-(4-fluorophenyl)-4-methylsulfonylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCS(C)(=O)=O)C=2C=CC(F)=CC=2)=C1 KWAIIOSCYWCVPV-UHFFFAOYSA-N 0.000 description 1
VPHKIZAGZQGSTC-UHFFFAOYSA-N n-[2-(4-methoxyphenyl)-4-[4-(1-methylbenzimidazole-2-carbonyl)piperidin-1-yl]butyl]-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(CN(C)C(=O)C=1C=CC=CC=1)CCN1CCC(C(=O)C=2N(C3=CC=CC=C3N=2)C)CC1 VPHKIZAGZQGSTC-UHFFFAOYSA-N 0.000 description 1
GGECTVCMAZBDSV-UHFFFAOYSA-N n-[2-(4-methoxyphenyl)-4-methylsulfonylbutyl]-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(CCS(C)(=O)=O)CN(C)C(=O)C1=CC=CC=C1 GGECTVCMAZBDSV-UHFFFAOYSA-N 0.000 description 1
MQJBKHACRLPQBA-UHFFFAOYSA-N n-[4-(4-benzhydrylidenepiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)=C(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=C(Cl)C(Cl)=CC=2)=C1 MQJBKHACRLPQBA-UHFFFAOYSA-N 0.000 description 1
APSAJGYOQVOWST-UHFFFAOYSA-N n-[4-(4-benzhydrylidenepiperidin-1-yl)-2-phenylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)=C(C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 APSAJGYOQVOWST-UHFFFAOYSA-N 0.000 description 1
OQSNTJDLUMLOKP-UHFFFAOYSA-N n-[4-[4-(1,3-benzothiazole-2-carbonyl)piperidin-1-yl]-2-(3,4-dichlorophenyl)butyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(CCN1CCC(CC1)C(=O)C=1SC2=CC=CC=C2N=1)C1=CC=C(Cl)C(Cl)=C1 OQSNTJDLUMLOKP-UHFFFAOYSA-N 0.000 description 1
YZKGKCVVSVNKKJ-UHFFFAOYSA-N n-[4-[4-(1-ethylbenzimidazole-2-carbonyl)piperidin-1-yl]-2-(4-fluorophenyl)butyl]-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CC)C=1C(=O)C(CC1)CCN1CCC(C=1C=CC(F)=CC=1)CN(C)C(=O)C1=CC=CC=C1 YZKGKCVVSVNKKJ-UHFFFAOYSA-N 0.000 description 1
FWFZDVGABVQSKU-UHFFFAOYSA-N n-[4-[4-(1h-benzimidazole-2-carbonyl)piperidin-1-yl]-2-(3,4-difluorophenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2NC3=CC=CC=C3N=2)C=2C=C(F)C(F)=CC=2)=C1 FWFZDVGABVQSKU-UHFFFAOYSA-N 0.000 description 1
ADFBZAFTANYUDH-UHFFFAOYSA-N n-[4-[4-(1h-benzimidazole-2-carbonyl)piperidin-1-yl]-2-(4-fluorophenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2NC3=CC=CC=C3N=2)C=2C=CC(F)=CC=2)=C1 ADFBZAFTANYUDH-UHFFFAOYSA-N 0.000 description 1
IFDJEELTYJTGFZ-UHFFFAOYSA-N n-[4-[4-[1-(2-ethoxyethyl)benzimidazole-2-carbonyl]piperidin-1-yl]-2-(3-methoxyphenyl)butyl]-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C=1C=C(OC)C=CC=1)CN(C)C(=O)C1=CC=CC=C1 IFDJEELTYJTGFZ-UHFFFAOYSA-N 0.000 description 1
VKFMISFDLHDQRP-UHFFFAOYSA-N n-[4-[4-[1-(2-ethoxyethyl)benzimidazole-2-carbonyl]piperidin-1-yl]-2-phenylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(=O)C(CC1)CCN1CCC(C=1C=CC=CC=1)CN(C)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 VKFMISFDLHDQRP-UHFFFAOYSA-N 0.000 description 1
RMAMQAMCNRTVSJ-UHFFFAOYSA-N n-[4-[4-[1-(furan-3-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]-2-phenylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(CC2)C(=O)C=2N(C3=CC=CC=C3N=2)CC2=COC=C2)C=2C=CC=CC=2)=C1 RMAMQAMCNRTVSJ-UHFFFAOYSA-N 0.000 description 1
AMWAHRNKIAYLGQ-UHFFFAOYSA-N n-[4-[4-[1-(furan-3-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]-2-phenylbutyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC=1C=COC=1 AMWAHRNKIAYLGQ-UHFFFAOYSA-N 0.000 description 1
PLEMUXYNFLEJRN-UHFFFAOYSA-N n-[4-[4-[1-[(1-benzylimidazol-2-yl)methyl]benzimidazole-2-carbonyl]piperidin-1-yl]-2-phenylbutyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=NC=CN1CC1=CC=CC=C1 PLEMUXYNFLEJRN-UHFFFAOYSA-N 0.000 description 1
JPHNXAKCIRRZRN-UHFFFAOYSA-N n-[4-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]-2-phenylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCN2CCC(O)(CC2)C=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)C=2C=CC=CC=2)=C1 JPHNXAKCIRRZRN-UHFFFAOYSA-N 0.000 description 1
LRGBJQLQSZTTJE-UHFFFAOYSA-N n-[4-[4-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-4-hydroxypiperidin-1-yl]-2-phenylbutyl]-n-methylbenzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1(O)C1=NC2=CC=CC=C2N1CC1=CC=C(F)C=C1 LRGBJQLQSZTTJE-UHFFFAOYSA-N 0.000 description 1
NPLVRMNSUQHKHQ-UHFFFAOYSA-N n-[4-[4-[1-[2-(furan-2-ylmethoxy)ethyl]benzimidazole-2-carbonyl]piperidin-1-yl]-2-(4-methoxyphenyl)butyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C(CN(C)C(=O)C=1C=C(OC)C(OC)=C(OC)C=1)CCN1CCC(C(=O)C=2N(C3=CC=CC=C3N=2)CCOCC=2OC=CC=2)CC1 NPLVRMNSUQHKHQ-UHFFFAOYSA-N 0.000 description 1
AFKJITSVXFNHQK-UHFFFAOYSA-N n-[4-[tert-butyl(dimethyl)silyl]oxy-2-pyridin-3-ylbutyl]-3,4,5-trimethoxy-n-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N(C)CC(CCO[Si](C)(C)C(C)(C)C)C=2C=NC=CC=2)=C1 AFKJITSVXFNHQK-UHFFFAOYSA-N 0.000 description 1
POVXOWVFLAAVBH-UHFFFAOYSA-N n-formamidoformamide Chemical compound O=CNNC=O POVXOWVFLAAVBH-UHFFFAOYSA-N 0.000 description 1
ZSGSMBJUYJENJR-UHFFFAOYSA-N n-methyl-n-[2-phenyl-4-[4-[1-(pyridin-2-ylmethyl)benzimidazole-2-carbonyl]piperidin-1-yl]butyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C)CC(C=1C=CC=CC=1)CCN(CC1)CCC1C(=O)C1=NC2=CC=CC=C2N1CC1=CC=CC=N1 ZSGSMBJUYJENJR-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-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
125000002524 organometallic group Chemical group 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
239000002245 particle Substances 0.000 description 1
238000005453 pelletization Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 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
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 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
UBPBYCIVVATUTK-UHFFFAOYSA-N piperidin-4-yl-[1-[2-(2,2,2-trifluoroethoxy)ethyl]benzimidazol-2-yl]methanone;hydroiodide Chemical compound I.N=1C2=CC=CC=C2N(CCOCC(F)(F)F)C=1C(=O)C1CCNCC1 UBPBYCIVVATUTK-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
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 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
235000015320 potassium carbonate Nutrition 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
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
150000003222 pyridines Chemical class 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
238000010791 quenching Methods 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000007115 recruitment Effects 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
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
239000002002 slurry Substances 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
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate 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
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
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 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
229930192474 thiophene Natural products 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
229960001262 tramazoline Drugs 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
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000008243 triphasic system Substances 0.000 description 1
230000009959 type I hypersensitivity Effects 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
210000000264 venule Anatomy 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1