ZA200203255B - Hydroxamic acid derivative as inhibitor of the formation of soluble human CD23. - Google Patents

Hydroxamic acid derivative as inhibitor of the formation of soluble human CD23. Download PDF

Info

Publication number: ZA200203255B
Authority: ZA; South Africa
Prior art keywords: compound; formula; disorders; dose; naphthylmethyl
Prior art date: 1999-10-27

Application number

ZA200203255A

Other languages

English (en)

Inventor

Andrew Faller

Ward John Gerard

Original Assignee

Smithkline Beecham Plc

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.)

1999-10-27

Filing date

2002-04-24

Publication date

2003-03-20

2002-04-24 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

2003-03-20 Publication of ZA200203255B publication Critical patent/ZA200203255B/en

Links

101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 title description 28
102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 title description 27
241000282414 Homo sapiens Species 0.000 title description 17
239000003112 inhibitor Substances 0.000 title description 13
230000015572 biosynthetic process Effects 0.000 title description 12
239000002253 acid Substances 0.000 title description 4
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 title description 3
150000001875 compounds Chemical class 0.000 claims description 74
238000000034 method Methods 0.000 claims description 22
208000026935 allergic disease Diseases 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
208000023275 Autoimmune disease Diseases 0.000 claims description 7
206010020751 Hypersensitivity Diseases 0.000 claims description 7
230000007815 allergy Effects 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
208000035475 disorder Diseases 0.000 claims description 7
208000027866 inflammatory disease Diseases 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
238000012261 overproduction Methods 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
238000011321 prophylaxis Methods 0.000 claims description 6
239000003814 drug Substances 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 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
239000000203 mixture Substances 0.000 description 28
239000000243 solution Substances 0.000 description 25
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
238000012360 testing method Methods 0.000 description 17
125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 15
210000004027 cell Anatomy 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
239000012528 membrane Substances 0.000 description 9
230000000694 effects Effects 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
210000001616 monocyte Anatomy 0.000 description 8
239000000047 product Substances 0.000 description 8
108060005980 Collagenase Proteins 0.000 description 7
102000029816 Collagenase Human genes 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
-1 alkali metal salts Chemical class 0.000 description 7
229960002424 collagenase Drugs 0.000 description 7
239000012634 fragment Substances 0.000 description 7
238000001802 infusion Methods 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
239000011734 sodium Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
238000003556 assay Methods 0.000 description 6
210000003719 b-lymphocyte Anatomy 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
210000000170 cell membrane Anatomy 0.000 description 6
239000003981 vehicle Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
206010061218 Inflammation Diseases 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000012267 brine Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
230000004054 inflammatory process Effects 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 4
102000008186 Collagen Human genes 0.000 description 4
108010035532 Collagen Proteins 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
229920001436 collagen Polymers 0.000 description 4
239000002158 endotoxin Substances 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
230000036470 plasma concentration Effects 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000007017 scission Effects 0.000 description 4
241000282472 Canis lupus familiaris Species 0.000 description 3
108090000695 Cytokines Proteins 0.000 description 3
102000004127 Cytokines Human genes 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000003125 aqueous solvent Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
238000013461 design Methods 0.000 description 3
238000011049 filling Methods 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
229920006008 lipopolysaccharide Polymers 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
229920001542 oligosaccharide Polymers 0.000 description 3
238000003305 oral gavage Methods 0.000 description 3
239000008188 pellet Substances 0.000 description 3
210000003752 saphenous vein Anatomy 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
239000003826 tablet Substances 0.000 description 3
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 2
241000220479 Acacia Species 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-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
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
108010002352 Interleukin-1 Proteins 0.000 description 2
108090000978 Interleukin-4 Proteins 0.000 description 2
108090001005 Interleukin-6 Proteins 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
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
241000282567 Macaca fascicularis Species 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
102000005741 Metalloproteases Human genes 0.000 description 2
108010006035 Metalloproteases Proteins 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
108700012920 TNF Proteins 0.000 description 2
230000009471 action Effects 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
239000002585 base Substances 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
210000003979 eosinophil Anatomy 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
210000003191 femoral vein Anatomy 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
210000002540 macrophage Anatomy 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
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
229940055577 oleyl alcohol Drugs 0.000 description 2
XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000002797 proteolythic effect Effects 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
238000001665 trituration Methods 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
206010002198 Anaphylactic reaction Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
238000011891 EIA kit Methods 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
239000004150 EU approved colour Substances 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
108010026132 Gelatinases Proteins 0.000 description 1
102000013382 Gelatinases Human genes 0.000 description 1
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
206010018910 Haemolysis Diseases 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
108010073816 IgE Receptors Proteins 0.000 description 1
102000009438 IgE Receptors Human genes 0.000 description 1
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 1
102100022338 Integrin alpha-M Human genes 0.000 description 1
102100022297 Integrin alpha-X Human genes 0.000 description 1
HUYWAWARQUIQLE-UHFFFAOYSA-N Isoetharine Chemical compound CC(C)NC(CC)C(O)C1=CC=C(O)C(O)=C1 HUYWAWARQUIQLE-UHFFFAOYSA-N 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
208000018569 Respiratory Tract disease Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
239000000150 Sympathomimetic Substances 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
XNRNNGPBEPRNAR-UHFFFAOYSA-N Thromboxane B2 Natural products CCCCCC(O)C=CC1OC(O)CC(O)C1CC=CCCCC(O)=O XNRNNGPBEPRNAR-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000001919 adrenal effect Effects 0.000 description 1
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
229960003556 aminophylline Drugs 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
230000036783 anaphylactic response Effects 0.000 description 1
208000003455 anaphylaxis Diseases 0.000 description 1
230000001088 anti-asthma Effects 0.000 description 1
239000000924 antiasthmatic agent Substances 0.000 description 1
230000030741 antigen processing and presentation Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
210000001772 blood platelet Anatomy 0.000 description 1
238000010241 blood sampling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
239000000168 bronchodilator agent Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
230000003491 cAMP production Effects 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000001175 calcium sulphate Substances 0.000 description 1
235000011132 calcium sulphate Nutrition 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
229960000258 corticotropin Drugs 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
125000001664 diethylamino group Chemical class [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000003828 downregulation Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000008157 edible vegetable oil Substances 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
239000000839 emulsion Substances 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
208000024711 extrinsic asthma Diseases 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000000499 gel Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000008588 hemolysis Effects 0.000 description 1
239000011539 homogenization buffer Substances 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000036039 immunity Effects 0.000 description 1
230000003308 immunostimulating effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
230000017306 interleukin-6 production Effects 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229960001268 isoetarine Drugs 0.000 description 1
229960001317 isoprenaline Drugs 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
210000001821 langerhans cell Anatomy 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
239000002523 lectin 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
229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
210000003712 lysosome Anatomy 0.000 description 1
230000001868 lysosomic effect Effects 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
150000002690 malonic acid derivatives Chemical class 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000007721 medicinal effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 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
150000007522 mineralic acids Chemical class 0.000 description 1
239000003607 modifier Substances 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000000822 natural killer cell Anatomy 0.000 description 1
229910052754 neon Inorganic materials 0.000 description 1
GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229960001802 phenylephrine Drugs 0.000 description 1
SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
239000008057 potassium phosphate buffer Substances 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000003380 propellant Substances 0.000 description 1
229960000380 propiolactone Drugs 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
229960002052 salbutamol Drugs 0.000 description 1
238000007789 sealing Methods 0.000 description 1
239000013049 sediment Substances 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940080313 sodium starch Drugs 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
239000012453 solvate Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000005477 standard model Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
229940032147 starch Drugs 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
108091007196 stromelysin Proteins 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
210000001179 synovial fluid Anatomy 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000002278 tabletting lubricant Substances 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000009827 uniform distribution Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Immunology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pain & Pain Management (AREA)
Transplantation (AREA)
Rheumatology (AREA)
Pulmonology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)

ZA200203255A 1999-10-27 2002-04-24 Hydroxamic acid derivative as inhibitor of the formation of soluble human CD23. ZA200203255B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9925470.8A GB9925470D0 (en)	1999-10-27	1999-10-27	Novel compounds

Publications (1)

Publication Number	Publication Date
ZA200203255B true ZA200203255B (en)	2003-03-20

Family

ID=10863507

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200203255A ZA200203255B (en)	1999-10-27	2002-04-24	Hydroxamic acid derivative as inhibitor of the formation of soluble human CD23.

Country Status (32)

Country	Link
US (2)	US6673965B1 (es)
EP (1)	EP1224164B1 (es)
JP (1)	JP3922431B2 (es)
KR (1)	KR20020044578A (es)
CN (1)	CN1182107C (es)
AR (1)	AR026244A1 (es)
AT (1)	ATE284382T1 (es)
AU (1)	AU766072B2 (es)
BR (1)	BR0015082A (es)
CA (1)	CA2389319A1 (es)
CO (1)	CO5261576A1 (es)
CZ (1)	CZ20021424A3 (es)
DE (1)	DE60016622T2 (es)
DK (1)	DK1224164T3 (es)
ES (1)	ES2233474T3 (es)
GB (1)	GB9925470D0 (es)
GC (1)	GC0000142A (es)
HK (1)	HK1049146A1 (es)
HU (1)	HUP0203270A3 (es)
IL (1)	IL149364A0 (es)
MX (1)	MXPA02004228A (es)
MY (1)	MY133601A (es)
NO (1)	NO20021965L (es)
NZ (1)	NZ518566A (es)
PE (1)	PE20010898A1 (es)
PL (1)	PL356524A1 (es)
PT (1)	PT1224164E (es)
SI (1)	SI1224164T1 (es)
TW (1)	TW561141B (es)
UY (1)	UY26416A1 (es)
WO (1)	WO2001030747A1 (es)
ZA (1)	ZA200203255B (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP5524215B2 (ja)	2008-09-19	2014-06-18	ファイザー・インク	抗菌剤として有用なヒドロキサム酸誘導体
EP2507266B1 (en)	2009-12-01	2015-02-18	Boston Medical Center Corporation	TREATMENT OF IgE-MEDIATED DISEASE
PT2512474E (pt)	2009-12-16	2014-12-23	Pfizer	Derivados de ácido hidroxâmico n-ligado úteis como agentes antibacterianos
CN104529883A (zh)	2011-03-07	2015-04-22	辉瑞大药厂	可用作抗菌剂的氟吡啶酮衍生物
WO2012137094A1 (en)	2011-04-08	2012-10-11	Pfizer Inc.	Isoxazole derivatives useful as antibacterial agents
MX2013011432A (es)	2011-04-08	2013-12-09	Pfizer	Derivados de imidazol, pirazol, y triazol utiles como agentes antibacterianos.
EP2525213A1 (en) *	2011-05-16	2012-11-21	Renishaw plc	Spectroscopic apparatus and methods for determining components present in a sample

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9513331D0 (en)	1995-06-30	1995-09-06	British Biotech Pharm	Matrix metalloproteinase inhibitors
GB9813451D0 (en) *	1998-06-22	1998-08-19	Smithkline Beecham Plc	Novel compounds

1999
- 1999-10-27 GB GBGB9925470.8A patent/GB9925470D0/en not_active Ceased
2000
- 2000-10-25 PL PL00356524A patent/PL356524A1/xx unknown
- 2000-10-25 MX MXPA02004228A patent/MXPA02004228A/es active IP Right Grant
- 2000-10-25 BR BR0015082-7A patent/BR0015082A/pt not_active IP Right Cessation
- 2000-10-25 PT PT00975954T patent/PT1224164E/pt unknown
- 2000-10-25 KR KR1020027005340A patent/KR20020044578A/ko not_active Application Discontinuation
- 2000-10-25 WO PCT/EP2000/010649 patent/WO2001030747A1/en active IP Right Grant
- 2000-10-25 ES ES00975954T patent/ES2233474T3/es not_active Expired - Lifetime
- 2000-10-25 DE DE60016622T patent/DE60016622T2/de not_active Expired - Lifetime
- 2000-10-25 AU AU13895/01A patent/AU766072B2/en not_active Ceased
- 2000-10-25 IL IL14936400A patent/IL149364A0/xx unknown
- 2000-10-25 JP JP2001533102A patent/JP3922431B2/ja not_active Expired - Fee Related
- 2000-10-25 US US10/111,209 patent/US6673965B1/en not_active Expired - Fee Related
- 2000-10-25 CZ CZ20021424A patent/CZ20021424A3/cs unknown
- 2000-10-25 AR ARP000105622A patent/AR026244A1/es not_active Application Discontinuation
- 2000-10-25 NZ NZ518566A patent/NZ518566A/en unknown
- 2000-10-25 CA CA002389319A patent/CA2389319A1/en not_active Abandoned
- 2000-10-25 GC GCP2000972 patent/GC0000142A/xx active
- 2000-10-25 AT AT00975954T patent/ATE284382T1/de not_active IP Right Cessation
- 2000-10-25 UY UY26416A patent/UY26416A1/es not_active Application Discontinuation
- 2000-10-25 EP EP00975954A patent/EP1224164B1/en not_active Expired - Lifetime
- 2000-10-25 MY MYPI20005012A patent/MY133601A/en unknown
- 2000-10-25 DK DK00975954T patent/DK1224164T3/da active
- 2000-10-25 HU HU0203270A patent/HUP0203270A3/hu unknown
- 2000-10-25 SI SI200030603T patent/SI1224164T1/xx unknown
- 2000-10-25 CN CNB008173680A patent/CN1182107C/zh not_active Expired - Fee Related
- 2000-10-26 CO CO00081571A patent/CO5261576A1/es not_active Application Discontinuation
- 2000-10-26 TW TW089122497A patent/TW561141B/zh active
- 2000-10-27 PE PE2000001156A patent/PE20010898A1/es not_active Application Discontinuation
2002
- 2002-04-24 ZA ZA200203255A patent/ZA200203255B/en unknown
- 2002-04-25 NO NO20021965A patent/NO20021965L/no unknown
- 2002-12-19 HK HK02109235A patent/HK1049146A1/xx not_active IP Right Cessation
2003
- 2003-10-03 US US10/678,679 patent/US20040077727A1/en not_active Abandoned

Also Published As

Publication number	Publication date
AU1389501A (en)	2001-05-08
UY26416A1 (es)	2001-05-31
US6673965B1 (en)	2004-01-06
TW561141B (en)	2003-11-11
CO5261576A1 (es)	2003-03-31
MXPA02004228A (es)	2002-10-17
GC0000142A (en)	2005-06-29
PT1224164E (pt)	2005-04-29
MY133601A (en)	2007-11-30
ES2233474T3 (es)	2005-06-16
HK1049146A1 (en)	2003-05-02
PL356524A1 (en)	2004-06-28
CA2389319A1 (en)	2001-05-03
US20040077727A1 (en)	2004-04-22
NO20021965L (no)	2002-06-13
HUP0203270A2 (hu)	2003-02-28
DE60016622D1 (de)	2005-01-13
IL149364A0 (en)	2002-11-10
DE60016622T2 (de)	2005-11-03
EP1224164A1 (en)	2002-07-24
WO2001030747A1 (en)	2001-05-03
NZ518566A (en)	2004-02-27
AR026244A1 (es)	2003-02-05
JP3922431B2 (ja)	2007-05-30
BR0015082A (pt)	2003-04-15
DK1224164T3 (da)	2005-03-29
GB9925470D0 (en)	1999-12-29
JP2003512450A (ja)	2003-04-02
CZ20021424A3 (cs)	2002-09-11
HUP0203270A3 (en)	2003-11-28
CN1182107C (zh)	2004-12-29
PE20010898A1 (es)	2001-10-13
AU766072B2 (en)	2003-10-09
CN1411436A (zh)	2003-04-16
ATE284382T1 (de)	2004-12-15
EP1224164B1 (en)	2004-12-08
KR20020044578A (ko)	2002-06-15
SI1224164T1 (en)	2005-06-30
NO20021965D0 (no)	2002-04-25

Publication	Publication Date	Title
US6242467B1 (en)	2001-06-05	Compounds
EP0918747B1 (en)	2003-08-06	INHIBITORS OF THE PRODUCTION OF s-CD23 AND THE SECRETION OF TNF
EP1224164B1 (en)	2004-12-08	Hydroxamic acid derivative as inhibitor of the formation of soluble human cd23
US20030195191A1 (en)	2003-10-16	N-sulfonyl hydroxamic acid derivatives as inhibitors of cd23
US20050085505A1 (en)	2005-04-21	Quinoline derivatives, process for preparing them and use for the treatment of diseases mediated by s-cd23
AU725056B2 (en)	2000-10-05	Hydroxamic acid based collagenase inhibitors
JP2000510138A (ja)	2000-08-08	ヒドロキサム酸をベースとするｃｄ２３およびｔｎｆ形成の阻害剤
US20040209822A1 (en)	2004-10-21	Novel compounds
WO2001044221A1 (en)	2001-06-21	Hydroxamic acid derivatives as inhibitors of human cd23 and of the tnf release
ES2243783T3 (es)	2005-12-01	Derivados de sulfona apropiadas para el tratamiento de enfermedades autoinmunes y alergias.
EP0909169A1 (en)	1999-04-21	Medical use
US20020082200A1 (en)	2002-06-27	Use of inhibitors of human S-CD23