UA80996C2 - Tricyclic derivatives as ltd4 antagonists, process for the preparation thereof, intermediate, pharmaceutical composition based thereon, use thereof - Google Patents

Tricyclic derivatives as ltd4 antagonists, process for the preparation thereof, intermediate, pharmaceutical composition based thereon, use thereof Download PDF

Info

Publication number: UA80996C2
Authority: UA; Ukraine
Prior art keywords: dihydro; acid; difluoroquinolin; group; stage
Prior art date: 2002-11-12

Application number

UAA200505509A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Almirall Prodespharma S A

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-11-12

Filing date

2003-11-11

Publication date

2007-11-26

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=32309630&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA80996(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2003-11-11 Application filed by Almirall Prodespharma S A filed Critical Almirall Prodespharma S A

2007-11-26 Publication of UA80996C2 publication Critical patent/UA80996C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 48
238000002360 preparation method Methods 0.000 title claims description 47
239000005557 antagonist Substances 0.000 title claims description 9
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
230000008569 process Effects 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 214
150000003839 salts Chemical class 0.000 claims abstract description 14
230000002265 prevention Effects 0.000 claims abstract description 8
238000004519 manufacturing process Methods 0.000 claims abstract description 7
208000026935 allergic disease Diseases 0.000 claims abstract description 5
208000027866 inflammatory disease Diseases 0.000 claims abstract 2
-1 hydroxy- Chemical class 0.000 claims description 162
239000002253 acid Substances 0.000 claims description 77
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 50
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 50
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 40
125000001424 substituent group Chemical group 0.000 claims description 40
125000000217 alkyl group Chemical group 0.000 claims description 34
229920002554 vinyl polymer Polymers 0.000 claims description 32
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 29
125000005843 halogen group Chemical group 0.000 claims description 28
125000003545 alkoxy group Chemical group 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 19
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
235000019260 propionic acid Nutrition 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
201000010099 disease Diseases 0.000 claims description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
230000001575 pathological effect Effects 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
125000003831 tetrazolyl group Chemical group 0.000 claims description 9
208000019695 Migraine disease Diseases 0.000 claims description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 8
206010027599 migraine Diseases 0.000 claims description 8
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
208000024780 Urticaria Diseases 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
230000000172 allergic effect Effects 0.000 claims description 7
208000006673 asthma Diseases 0.000 claims description 7
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
239000005711 Benzoic acid Substances 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
235000010233 benzoic acid Nutrition 0.000 claims description 6
KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 claims description 5
206010006448 Bronchiolitis Diseases 0.000 claims description 5
201000003883 Cystic fibrosis Diseases 0.000 claims description 5
206010012438 Dermatitis atopic Diseases 0.000 claims description 5
208000001640 Fibromyalgia Diseases 0.000 claims description 5
208000005615 Interstitial Cystitis Diseases 0.000 claims description 5
206010039085 Rhinitis allergic Diseases 0.000 claims description 5
206010039094 Rhinitis perennial Diseases 0.000 claims description 5
208000002365 Viral Bronchiolitis Diseases 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 5
125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 5
125000002877 alkyl aryl group Chemical group 0.000 claims description 5
125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims description 5
201000010105 allergic rhinitis Diseases 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
230000008485 antagonism Effects 0.000 claims description 5
201000008937 atopic dermatitis Diseases 0.000 claims description 5
125000004663 dialkyl amino group Chemical group 0.000 claims description 5
201000001564 eosinophilic gastroenteritis Diseases 0.000 claims description 5
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 5
208000022719 perennial allergic rhinitis Diseases 0.000 claims description 5
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 4
ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000003112 inhibitor Substances 0.000 claims description 4
229940126601 medicinal product Drugs 0.000 claims description 4
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 3
LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 3
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 3
LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 claims description 2
244000028419 Styrax benzoin Species 0.000 claims description 2
235000000126 Styrax benzoin Nutrition 0.000 claims description 2
235000008411 Sumatra benzointree Nutrition 0.000 claims description 2
229960002130 benzoin Drugs 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
235000019382 gum benzoic Nutrition 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
108010047623 iridine Proteins 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 claims 1
230000001668 ameliorated effect Effects 0.000 claims 1
OZYHLCOUAISLLG-UHFFFAOYSA-N cyclopropyl acetate Chemical compound CC(=O)OC1CC1 OZYHLCOUAISLLG-UHFFFAOYSA-N 0.000 claims 1
125000001183 hydrocarbyl group Chemical group 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
230000002757 inflammatory effect Effects 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
239000000203 mixture Substances 0.000 description 188
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 179
239000000243 solution Substances 0.000 description 130
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 121
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
239000000047 product Substances 0.000 description 96
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 89
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 59
239000007787 solid Substances 0.000 description 59
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 57
239000002904 solvent Substances 0.000 description 50
238000003756 stirring Methods 0.000 description 46
239000012044 organic layer Substances 0.000 description 45
125000004432 carbon atom Chemical group C* 0.000 description 44
239000000126 substance Substances 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
229940095574 propionic acid Drugs 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
150000003254 radicals Chemical class 0.000 description 24
230000015572 biosynthetic process Effects 0.000 description 21
239000007858 starting material Substances 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
238000003786 synthesis reaction Methods 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
238000010828 elution Methods 0.000 description 19
238000010992 reflux Methods 0.000 description 19
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
238000001816 cooling Methods 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
150000001412 amines Chemical class 0.000 description 16
125000001153 fluoro group Chemical group F* 0.000 description 16
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
239000003153 chemical reaction reagent Substances 0.000 description 14
239000012634 fragment Substances 0.000 description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
239000010410 layer Substances 0.000 description 14
239000012279 sodium borohydride Substances 0.000 description 14
229910000033 sodium borohydride Inorganic materials 0.000 description 14
DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 13
239000012047 saturated solution Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
239000003826 tablet Substances 0.000 description 12
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 12
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical class C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
150000001299 aldehydes Chemical class 0.000 description 10
238000002425 crystallisation Methods 0.000 description 10
230000008025 crystallization Effects 0.000 description 10
238000003818 flash chromatography Methods 0.000 description 10
150000002617 leukotrienes Chemical class 0.000 description 10
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
150000001263 acyl chlorides Chemical class 0.000 description 9
150000001298 alcohols Chemical class 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
150000007513 acids Chemical class 0.000 description 8
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 8
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
239000012298 atmosphere Substances 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
229910052731 fluorine Inorganic materials 0.000 description 7
150000002576 ketones Chemical class 0.000 description 7
239000000725 suspension Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
239000002841 Lewis acid Substances 0.000 description 6
230000002152 alkylating effect Effects 0.000 description 6
235000011114 ammonium hydroxide Nutrition 0.000 description 6
125000004429 atom Chemical group 0.000 description 6
238000009835 boiling Methods 0.000 description 6
150000001735 carboxylic acids Chemical class 0.000 description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
238000001035 drying Methods 0.000 description 6
150000002367 halogens Chemical group 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
150000007517 lewis acids Chemical class 0.000 description 6
239000007788 liquid Substances 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
150000002989 phenols Chemical class 0.000 description 6
239000011669 selenium Substances 0.000 description 6
150000003456 sulfonamides Chemical class 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 5
239000012267 brine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
230000009615 deamination Effects 0.000 description 5
238000006481 deamination reaction Methods 0.000 description 5
208000037765 diseases and disorders Diseases 0.000 description 5
239000011737 fluorine Substances 0.000 description 5
235000012907 honey Nutrition 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
125000002883 imidazolyl group Chemical group 0.000 description 5
238000002156 mixing Methods 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
235000012239 silicon dioxide Nutrition 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 5
UYQPSKUPEXAQRJ-UHFFFAOYSA-N 1-(chloromethyl)-4-phenylmethoxybenzene Chemical compound C1=CC(CCl)=CC=C1OCC1=CC=CC=C1 UYQPSKUPEXAQRJ-UHFFFAOYSA-N 0.000 description 4
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 4
229910015900 BF3 Inorganic materials 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
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 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
241000725643 Respiratory syncytial virus Species 0.000 description 4
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
229960002433 cysteine Drugs 0.000 description 4
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
125000002632 imidazolidinyl group Chemical group 0.000 description 4
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
239000008101 lactose Substances 0.000 description 4
229960001375 lactose Drugs 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
150000002828 nitro derivatives Chemical class 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
238000000746 purification Methods 0.000 description 4
125000000168 pyrrolyl group Chemical group 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
235000010288 sodium nitrite Nutrition 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 4
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
238000005303 weighing Methods 0.000 description 4
QQJODMUSGDSKPF-UHFFFAOYSA-N 2-(chloromethyl)benzaldehyde Chemical class ClCC1=CC=CC=C1C=O QQJODMUSGDSKPF-UHFFFAOYSA-N 0.000 description 3
CPAPVZHVFFWABW-UHFFFAOYSA-N 2-ethenyl-6,7-difluoroquinoline Chemical compound C1=C(C=C)N=C2C=C(F)C(F)=CC2=C1 CPAPVZHVFFWABW-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
239000004342 Benzoyl peroxide Substances 0.000 description 3
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
241000700198 Cavia Species 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
235000019400 benzoyl peroxide Nutrition 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
239000000872 buffer Substances 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
229910000024 caesium carbonate Inorganic materials 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
238000000576 coating method Methods 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
239000006071 cream Substances 0.000 description 3
XHRNQDMNINGCES-UHFFFAOYSA-N cyclohept-4-en-1-one Chemical compound O=C1CCC=CCC1 XHRNQDMNINGCES-UHFFFAOYSA-N 0.000 description 3
239000012954 diazonium Substances 0.000 description 3
150000001989 diazonium salts Chemical class 0.000 description 3
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
239000002609 medium Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229910052751 metal Chemical group 0.000 description 3
239000002184 metal Chemical group 0.000 description 3
210000004088 microvessel Anatomy 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
229960003512 nicotinic acid Drugs 0.000 description 3
239000011664 nicotinic acid Substances 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
230000035699 permeability Effects 0.000 description 3
125000004193 piperazinyl group Chemical group 0.000 description 3
229920000137 polyphosphoric acid Polymers 0.000 description 3
239000011591 potassium Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
125000003226 pyrazolyl group Chemical group 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 3
125000001425 triazolyl group Chemical group 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical class FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
MLIBGOFSXXWRIY-UHFFFAOYSA-N 1-(2-hydroxy-5-methoxyphenyl)ethanone Chemical compound COC1=CC=C(O)C(C(C)=O)=C1 MLIBGOFSXXWRIY-UHFFFAOYSA-N 0.000 description 2
125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
AJPAXHQSRCPYDQ-UHFFFAOYSA-N 2-(bromomethyl)-6,7-difluoroquinoline Chemical compound C1=C(CBr)N=C2C=C(F)C(F)=CC2=C1 AJPAXHQSRCPYDQ-UHFFFAOYSA-N 0.000 description 2
125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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 2
GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-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
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
206010002091 Anaesthesia Diseases 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
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 2
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
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 2
241001465754 Metazoa Species 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 2
229930006000 Sucrose Natural products 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
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
201000009961 allergic asthma Diseases 0.000 description 2
BCDGQXUMWHRQCB-UHFFFAOYSA-N aminoacetone Chemical compound CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
230000037005 anaesthesia Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
230000027455 binding Effects 0.000 description 2
239000001045 blue dye Substances 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
210000000621 bronchi Anatomy 0.000 description 2
238000005251 capillar electrophoresis Methods 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
229910052681 coesite Inorganic materials 0.000 description 2
229940075614 colloidal silicon dioxide Drugs 0.000 description 2
229910052906 cristobalite Inorganic materials 0.000 description 2
239000012043 crude product Substances 0.000 description 2
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 2
238000010586 diagram Methods 0.000 description 2
FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
238000002845 discoloration Methods 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
238000009826 distribution Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 2
229960003699 evans blue Drugs 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000000945 filler Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000008187 granular material Substances 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
239000012535 impurity Substances 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
229960001021 lactose monohydrate Drugs 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 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
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
125000001715 oxadiazolyl group Chemical group 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
125000002971 oxazolyl group Chemical group 0.000 description 2
125000000466 oxiranyl group Chemical group 0.000 description 2
NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
239000012071 phase Substances 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
125000005936 piperidyl group Chemical group 0.000 description 2
229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
125000003072 pyrazolidinyl group Chemical group 0.000 description 2
125000002755 pyrazolinyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
125000001422 pyrrolinyl group Chemical group 0.000 description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 2
206010039083 rhinitis Diseases 0.000 description 2
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001587 sorbitan monostearate Substances 0.000 description 2
235000011076 sorbitan monostearate Nutrition 0.000 description 2
229940035048 sorbitan monostearate Drugs 0.000 description 2
229910052682 stishovite Inorganic materials 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
229940124530 sulfonamide Drugs 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
125000001113 thiadiazolyl group Chemical group 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
125000004568 thiomorpholinyl group Chemical group 0.000 description 2
239000004408 titanium dioxide Substances 0.000 description 2
210000003437 trachea Anatomy 0.000 description 2
230000007704 transition Effects 0.000 description 2
229910052905 tridymite Inorganic materials 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
YUIOPHXTILULQC-UHFFFAOYSA-N 1,4-Dithiane-2,5-diol Chemical class OC1CSC(O)CS1 YUIOPHXTILULQC-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
MXQNNPVWCMVPPS-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)ethanethiol Chemical compound SCCC1=NN=NN1 MXQNNPVWCMVPPS-UHFFFAOYSA-N 0.000 description 1
UPHXHPZMPYZDHC-UHFFFAOYSA-N 2-(bromomethyl)-7-chloro-6-fluoroquinoline Chemical compound C1=C(CBr)N=C2C=C(Cl)C(F)=CC2=C1 UPHXHPZMPYZDHC-UHFFFAOYSA-N 0.000 description 1
FOVGXLBHPDGJCN-UHFFFAOYSA-N 2-[2-(4-methoxyphenyl)ethyl]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CCC1=NC=CC=C1C(O)=O FOVGXLBHPDGJCN-UHFFFAOYSA-N 0.000 description 1
OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
XUGNJOCQALIQFG-UHFFFAOYSA-N 2-ethenylquinoline Chemical compound C1=CC=CC2=NC(C=C)=CC=C21 XUGNJOCQALIQFG-UHFFFAOYSA-N 0.000 description 1
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
HNTZKNJGAFJMHQ-UHFFFAOYSA-N 2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=CC=C1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
BSSLVCQAYWTRRC-UHFFFAOYSA-N 3-(bromomethyl)pyridine-2-carbonitrile Chemical compound BrCC1=CC=CN=C1C#N BSSLVCQAYWTRRC-UHFFFAOYSA-N 0.000 description 1
UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
ASCWVQXSKGOWHV-UHFFFAOYSA-N 3-(sulfanylmethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(CS)=C1 ASCWVQXSKGOWHV-UHFFFAOYSA-N 0.000 description 1
IVRTUHPMWXWCGL-UHFFFAOYSA-N 3-[(4-bromophenoxy)methyl]pyridine-2-carbonitrile Chemical compound C1=CC(Br)=CC=C1OCC1=CC=CN=C1C#N IVRTUHPMWXWCGL-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
GNHMRTZZNHZDDM-UHFFFAOYSA-N 3-chloropropionitrile Chemical compound ClCCC#N GNHMRTZZNHZDDM-UHFFFAOYSA-N 0.000 description 1
ZBQGMMDOBGOEHH-UHFFFAOYSA-N 3-methyl-3-sulfanylbutanoic acid Chemical compound CC(C)(S)CC(O)=O ZBQGMMDOBGOEHH-UHFFFAOYSA-N 0.000 description 1
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 1
OEBIVOHKFYSBPE-UHFFFAOYSA-N 4-Benzyloxybenzyl alcohol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC=C1 OEBIVOHKFYSBPE-UHFFFAOYSA-N 0.000 description 1
ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
DTRIDVOOPAQEEL-UHFFFAOYSA-N 4-sulfanylbutanoic acid Chemical compound OC(=O)CCCS DTRIDVOOPAQEEL-UHFFFAOYSA-N 0.000 description 1
YWMOOBWNYVFLKH-UHFFFAOYSA-N 6,7-difluoro-2-methylquinoline Chemical compound C1=C(F)C(F)=CC2=NC(C)=CC=C21 YWMOOBWNYVFLKH-UHFFFAOYSA-N 0.000 description 1
IDDIQDVSYHYORP-UHFFFAOYSA-N 6,7-difluoroquinoline Chemical compound C1=CN=C2C=C(F)C(F)=CC2=C1 IDDIQDVSYHYORP-UHFFFAOYSA-N 0.000 description 1
MVEOHWRUBFWKJY-UHFFFAOYSA-N 7-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(O)=CC=C21 MVEOHWRUBFWKJY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 1
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
108010001478 Bacitracin Proteins 0.000 description 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
229940124638 COX inhibitor Drugs 0.000 description 1
101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
CJQWLNNCQIHKHP-UHFFFAOYSA-N Ethyl 3-mercaptopropanoic acid Chemical compound CCOC(=O)CCS CJQWLNNCQIHKHP-UHFFFAOYSA-N 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
241000976806 Genea <ascomycete fungus> Species 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
102000003820 Lipoxygenases Human genes 0.000 description 1
108090000128 Lipoxygenases Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
101100498160 Mus musculus Dach1 gene Proteins 0.000 description 1
241000468053 Obodhiang virus Species 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
229920003776 Reny® Polymers 0.000 description 1
NQHAZTDQFIYTQD-UHFFFAOYSA-N SOS Chemical compound SOS NQHAZTDQFIYTQD-UHFFFAOYSA-N 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
241000272534 Struthio camelus Species 0.000 description 1
244000186561 Swietenia macrophylla Species 0.000 description 1
241000218636 Thuja Species 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
101710162629 Trypsin inhibitor Proteins 0.000 description 1
229940122618 Trypsin inhibitor Drugs 0.000 description 1
241000256856 Vespidae Species 0.000 description 1
YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910001963 alkali metal nitrate Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000005427 anthranyl group Chemical group 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229940114079 arachidonic acid Drugs 0.000 description 1
235000021342 arachidonic acid Nutrition 0.000 description 1
150000003975 aryl alkyl amines Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
229960003071 bacitracin Drugs 0.000 description 1
229930184125 bacitracin Natural products 0.000 description 1
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 1
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
239000004044 bronchoconstricting agent Substances 0.000 description 1
230000003435 bronchoconstrictive effect Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
FGNLEIGUMSBZQP-UHFFFAOYSA-N cadaverine dihydrochloride Chemical compound Cl.Cl.NCCCCCN FGNLEIGUMSBZQP-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000004452 carbocyclyl group Chemical group 0.000 description 1
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical compound OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
230000003399 chemotactic effect Effects 0.000 description 1
239000012320 chlorinating reagent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000011278 co-treatment Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000000748 compression moulding Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 1
MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 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
BOTLEXFFFSMRLQ-UHFFFAOYSA-N cyclopentyloxycyclopentane Chemical compound C1CCCC1OC1CCCC1 BOTLEXFFFSMRLQ-UHFFFAOYSA-N 0.000 description 1
229960001305 cysteine hydrochloride Drugs 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000000975 dye Substances 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
RHFOYRRUVLOOJP-UHFFFAOYSA-N ethoxyethane;propanoic acid Chemical compound CCOCC.CCC(O)=O RHFOYRRUVLOOJP-UHFFFAOYSA-N 0.000 description 1
ZDXGKCWPISPQIQ-UHFFFAOYSA-N ethyl 4-methylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=CC=C1C ZDXGKCWPISPQIQ-UHFFFAOYSA-N 0.000 description 1
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000004744 fabric Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
150000003948 formamides Chemical class 0.000 description 1
HLXVERDKKMHKLD-UHFFFAOYSA-N formylazanium;acetate Chemical compound NC=O.CC(O)=O HLXVERDKKMHKLD-UHFFFAOYSA-N 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
150000002527 isonitriles Chemical class 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
210000004731 jugular vein Anatomy 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
210000005246 left atrium Anatomy 0.000 description 1
210000005240 left ventricle Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
NRUBUZBAZRTHHX-UHFFFAOYSA-N lithium;propan-2-ylazanide Chemical compound [Li+].CC(C)[NH-] NRUBUZBAZRTHHX-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000155 melt Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
IRUDOFZPRBTTQY-UHFFFAOYSA-N methyl 2,2-dimethyl-3-sulfanylpropanoate Chemical compound COC(=O)C(C)(C)CS IRUDOFZPRBTTQY-UHFFFAOYSA-N 0.000 description 1
YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
CPXCDEMFNPKOEF-UHFFFAOYSA-N methyl 3-methylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1 CPXCDEMFNPKOEF-UHFFFAOYSA-N 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
230000000802 nitrating effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
230000009935 nitrosation Effects 0.000 description 1
238000007034 nitrosation reaction Methods 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
150000002940 palladium Chemical class 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
238000000053 physical method Methods 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
238000012552 review Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000013049 sediment Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
DWRGLIHFAJTMGM-UHFFFAOYSA-N thiohydroxylamine;hydrochloride Chemical compound Cl.SN DWRGLIHFAJTMGM-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000002792 vascular Effects 0.000 description 1
229940099259 vaseline Drugs 0.000 description 1
229960004764 zafirlukast Drugs 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Immunology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Oncology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Otolaryngology (AREA)
Communicable Diseases (AREA)
Biomedical Technology (AREA)
Virology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Polyurethanes Or Polyureas (AREA)
Paints Or Removers (AREA)

UAA200505509A 2002-11-12 2003-11-11 Tricyclic derivatives as ltd4 antagonists, process for the preparation thereof, intermediate, pharmaceutical composition based thereon, use thereof UA80996C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES200202590A ES2211315B1 (es)	2002-11-12	2002-11-12	Nuevos compuestos triciclicos.
PCT/EP2003/012581 WO2004043966A1 (en)	2002-11-12	2003-11-11	New tricyclic derivatives as ltd4 antagonists

Publications (1)

Publication Number	Publication Date
UA80996C2 true UA80996C2 (en)	2007-11-26

Family

ID=32309630

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UAA200505509A UA80996C2 (en)	2002-11-12	2003-11-11	Tricyclic derivatives as ltd4 antagonists, process for the preparation thereof, intermediate, pharmaceutical composition based thereon, use thereof

Country Status (19)

Country	Link
US (1)	US7557212B2 (de)
EP (1)	EP1560834B1 (de)
JP (1)	JP2006508116A (de)
KR (1)	KR20050074605A (de)
CN (1)	CN100379742C (de)
AT (1)	ATE399170T1 (de)
AU (1)	AU2003288032A1 (de)
BR (1)	BR0315462A (de)
CA (1)	CA2505491A1 (de)
CO (1)	CO5700775A2 (de)
DE (1)	DE60321810D1 (de)
EC (1)	ECSP055844A (de)
ES (2)	ES2211315B1 (de)
MX (1)	MXPA05005017A (de)
NO (1)	NO20052858L (de)
RU (1)	RU2330855C2 (de)
UA (1)	UA80996C2 (de)
WO (1)	WO2004043966A1 (de)
ZA (1)	ZA200503806B (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2165768B1 (es)	1999-07-14	2003-04-01	Almirall Prodesfarma Sa	Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen.
US7214687B2 (en)	1999-07-14	2007-05-08	Almirall Ag	Quinuclidine derivatives and medicinal compositions containing the same
RU2379033C2 (ru)	2004-05-31	2010-01-20	Лабораториос Альмираль, С.А.	Комбинации, содержащие антимускариновые средства и бета-адренергические агонисты
ES2257152B1 (es)	2004-05-31	2007-07-01	Laboratorios Almirall S.A.	Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos.
ATE524445T1 (de)	2005-06-23	2011-09-15	Merck Sharp & Dohme	Benzocycloheptapyridine als inhibitoren der tyrosinkinase met
JP2009513580A (ja) *	2005-10-21	2009-04-02	メルクエンドカムパニーインコーポレーテッド	チロシンキナーゼ阻害剤
TW200813021A (en)	2006-07-10	2008-03-16	Merck & Co Inc	Tyrosine kinase inhibitors
ES2298049B1 (es)	2006-07-21	2009-10-20	Laboratorios Almirall S.A.	Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano.
EP2100599A1 (de)	2008-03-13	2009-09-16	Laboratorios Almirall, S.A.	Inhalationszusammensetzung enthaltend Aclidinium zur Behandlung von Asthma sowie chronisch-obstruktiver Lungenerkrankung
EP2100598A1 (de)	2008-03-13	2009-09-16	Laboratorios Almirall, S.A.	Inhalationszusammensetzung enthaltend Aclidinium zur Behandlung von Asthma sowie chronisch-obstruktiver Lungenerkrankung
EP2108641A1 (de)	2008-04-11	2009-10-14	Laboratorios Almirall, S.A.	Neue substituierte Spiro[Cycloalkyl-1,3'-indo]-2'(1'H)-on-Derivate und ihre Verwendung als p38 mitogen-activated Kinase Inhibitoren
EP2113503A1 (de)	2008-04-28	2009-11-04	Laboratorios Almirall, S.A.	Neue substituierte Indolin-2-on- Derivate und ihre Verwendung als p39 mitogen-activated Kinase Inhibitoren
EP2322176A1 (de)	2009-11-11	2011-05-18	Almirall, S.A.	Neue 7-Phenyl-[1,2,4]triazol[4,3-a]pyridin-3(2H)on-Derivate
EP2510928A1 (de)	2011-04-15	2012-10-17	Almirall, S.A.	Aclidinium zur Verbesserung der Schlafqualität bei atemwegserkrankten Patienten
BR112014001760A2 (pt)	2011-07-26	2017-03-07	Sun Pharma Advanced Res Co Ltd	antagonistas de leucotrieno cisteínico
JP2019081709A (ja) *	2016-03-18	2019-05-30	石原産業株式会社	有害生物防除剤

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ228888A (en) *	1988-04-28	1991-12-23	Schering Corp	Derivatives of piperidine, piperidylidene and piperazine and pharmaceutical compositions
NZ234883A (en) *	1989-08-22	1995-01-27	Merck Frosst Canada Inc	Quinolin-2-ylmethoxy indole derivatives, preparation and pharmaceutical compositions thereof
AU674569B2 (en) *	1993-02-16	1997-01-02	Ube Industries, Ltd.	Quinoline derivative
NZ504218A (en) *	1997-11-25	2002-04-26	Schering Corp	Thrombin receptor antagonists
US20030216571A1 (en) *	1999-12-28	2003-11-20	Yoshiaki Kuroki	Tricyclic compounds
JP2006151809A (ja) *	2002-12-26	2006-06-15	Ube Ind Ltd	ベンゾシクロヘプタピリジン化合物

2002
- 2002-11-12 ES ES200202590A patent/ES2211315B1/es not_active Expired - Fee Related
2003
- 2003-11-11 BR BR0315462-9A patent/BR0315462A/pt not_active IP Right Cessation
- 2003-11-11 MX MXPA05005017A patent/MXPA05005017A/es not_active Application Discontinuation
- 2003-11-11 WO PCT/EP2003/012581 patent/WO2004043966A1/en not_active Ceased
- 2003-11-11 UA UAA200505509A patent/UA80996C2/uk unknown
- 2003-11-11 KR KR1020057008474A patent/KR20050074605A/ko not_active Withdrawn
- 2003-11-11 CN CNB2003801085261A patent/CN100379742C/zh not_active Expired - Fee Related
- 2003-11-11 JP JP2004550982A patent/JP2006508116A/ja active Pending
- 2003-11-11 RU RU2005118757/04A patent/RU2330855C2/ru not_active IP Right Cessation
- 2003-11-11 US US10/534,487 patent/US7557212B2/en not_active Expired - Fee Related
- 2003-11-11 ES ES03779886T patent/ES2306906T3/es not_active Expired - Lifetime
- 2003-11-11 AT AT03779886T patent/ATE399170T1/de not_active IP Right Cessation
- 2003-11-11 AU AU2003288032A patent/AU2003288032A1/en not_active Abandoned
- 2003-11-11 EP EP03779886A patent/EP1560834B1/de not_active Expired - Lifetime
- 2003-11-11 CA CA002505491A patent/CA2505491A1/en not_active Abandoned
- 2003-11-11 DE DE60321810T patent/DE60321810D1/de not_active Expired - Lifetime
2005
- 2005-05-11 ZA ZA200503806A patent/ZA200503806B/en unknown
- 2005-06-09 EC EC2005005844A patent/ECSP055844A/es unknown
- 2005-06-10 CO CO05056627A patent/CO5700775A2/es unknown
- 2005-06-13 NO NO20052858A patent/NO20052858L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
JP2006508116A (ja)	2006-03-09
NO20052858D0 (no)	2005-06-13
WO2004043966A1 (en)	2004-05-27
MXPA05005017A (es)	2005-08-03
DE60321810D1 (de)	2008-08-07
KR20050074605A (ko)	2005-07-18
ZA200503806B (en)	2006-08-30
CA2505491A1 (en)	2004-05-27
BR0315462A (pt)	2005-08-23
AU2003288032A1 (en)	2004-06-03
CN1735618A (zh)	2006-02-15
ES2306906T3 (es)	2008-11-16
RU2005118757A (ru)	2006-02-27
US7557212B2 (en)	2009-07-07
NO20052858L (no)	2005-08-12
ES2211315B1 (es)	2005-10-16
ES2211315A1 (es)	2004-07-01
EP1560834B1 (de)	2008-06-25
ATE399170T1 (de)	2008-07-15
US20060116363A1 (en)	2006-06-01
CO5700775A2 (es)	2006-11-30
EP1560834A1 (de)	2005-08-10
RU2330855C2 (ru)	2008-08-10
CN100379742C (zh)	2008-04-09
ECSP055844A (es)	2005-09-20

Publication	Publication Date	Title
US10941160B2 (en)	2021-03-09	Bromodomain inhibitors
CN114085212B (zh)	2023-05-02	异吲哚啉类化合物、其制备方法、药物组合物及用途
DE60315677T2 (de)	2008-06-05	Pyrazolopyridin derivate als tgf beta hemmstoffe zur behandlung von krebs
UA80996C2 (en)	2007-11-26	Tricyclic derivatives as ltd4 antagonists, process for the preparation thereof, intermediate, pharmaceutical composition based thereon, use thereof
US20190092761A1 (en)	2019-03-28	Methods and Compositions for Inhibition of Bromodomain and Extratermial Proteins
WO2014183555A1 (zh)	2014-11-20	环烷基甲酸类衍生物、其制备方法及其在医药上的应用
JP2012520246A (ja)	2012-09-06	Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノイソオキサゾロピリジン
CN115703761A (zh)	2023-02-17	作为wwp1抑制剂的化合物及其应用
CA3229293A1 (en)	2023-03-16	6-aza-quinoline derivatives and related uses
CN107074856A (zh)	2017-08-18	CaMKII抑制剂及其用途
TWI900672B (zh)	2025-10-11	乙醯胺基－苯基四唑衍生物及其使用方法
BR112017020739B1 (pt)	2023-03-14	Compostos fundidos tricíclicos de 1-cicloalquil piridin-2-ona, composição farmacêutica e seus usos
US12297193B2 (en)	2025-05-13	PTPN2/PTP1B degrader and therapeutic method thereof
JP6033788B2 (ja)	2016-11-30	置換されたメチルアミン、セロトニン５−ｈｔ６受容体アンタゴニスト、製造のための方法及びその使用
CA3089666A1 (en)	2019-08-08	Ghrelin o-acyltransferase inhibitors
CN114195800A (zh)	2022-03-18	Usp7抑制剂
TW202430505A (zh)	2024-08-01	萘醯胺類化合物、其製備方法及其應用
NZ539954A (en)	2007-11-30	New tricyclic derivatives as LTD4 antagonists
HK1147674B (en)	2014-09-19	Heterocyclic compounds as crth2 receptor antagonists
HK1147674A1 (en)	2011-08-19	Heterocyclic compounds as crth2 receptor antagonists