OA11838A - Gardos channel antagonists. - Google Patents

Gardos channel antagonists. Download PDF

Info

Publication number: OA11838A
Authority: OA; OAPI
Prior art keywords: substituent; acetamide; ring; compound; para
Prior art date: 1999-02-23

Application number

OA1200100220A

Other languages

English (en)

Inventor

Grant Andrew Mcnaughton-Smith

Gregory Cooksey Rigdon

Jonathan Walter Stocker

Original Assignee

Icagen Inc

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

1999-02-23

Filing date

2000-02-10

Publication date

2005-08-22

2000-02-10 Application filed by Icagen Inc filed Critical Icagen Inc

2005-08-22 Publication of OA11838A publication Critical patent/OA11838A/en

Links

239000005557 antagonist Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 201
238000000034 method Methods 0.000 claims abstract description 67
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 32
239000003112 inhibitor Substances 0.000 claims abstract description 31
230000004907 flux Effects 0.000 claims abstract description 23
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 14
239000011591 potassium Substances 0.000 claims abstract description 14
229910052700 potassium Inorganic materials 0.000 claims abstract description 14
229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
230000002401 inhibitory effect Effects 0.000 claims abstract description 10
108091006146 Channels Proteins 0.000 claims description 81
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 54
239000000203 mixture Substances 0.000 claims description 32
125000001424 substituent group Chemical group 0.000 claims description 20
-1 triarylmethyl radical Chemical class 0.000 claims description 17
102000004257 Potassium Channel Human genes 0.000 claims description 15
108020001213 potassium channel Proteins 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
239000008194 pharmaceutical composition Substances 0.000 claims description 13
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
229940125400 channel inhibitor Drugs 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
150000003254 radicals Chemical class 0.000 claims description 3
230000002708 enhancing effect Effects 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 3
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 2
150000005840 aryl radicals Chemical class 0.000 claims 2
POFWRMVFWIJXHP-UHFFFAOYSA-N n-benzyl-9-(oxan-2-yl)purin-6-amine Chemical compound C=1C=CC=CC=1CNC(C=1N=C2)=NC=NC=1N2C1CCCCO1 POFWRMVFWIJXHP-UHFFFAOYSA-N 0.000 claims 1
208000007056 sickle cell anemia Diseases 0.000 abstract description 17
238000001727 in vivo Methods 0.000 abstract description 13
239000011737 fluorine Substances 0.000 abstract description 9
210000003743 erythrocyte Anatomy 0.000 abstract description 8
230000015556 catabolic process Effects 0.000 abstract 1
238000006731 degradation reaction Methods 0.000 abstract 1
230000018044 dehydration Effects 0.000 abstract 1
238000006297 dehydration reaction Methods 0.000 abstract 1
210000004027 cell Anatomy 0.000 description 50
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 28
230000036515 potency Effects 0.000 description 27
239000003795 chemical substances by application Substances 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
238000005481 NMR spectroscopy Methods 0.000 description 21
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
230000000694 effects Effects 0.000 description 20
VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 19
229960004022 clotrimazole Drugs 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 16
230000005764 inhibitory process Effects 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
238000000338 in vitro Methods 0.000 description 14
238000003556 assay Methods 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000003814 drug Substances 0.000 description 11
238000006467 substitution reaction Methods 0.000 description 11
SUIKWZVCSWVADP-UHFFFAOYSA-N 2,2,2-triphenylacetamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N)C1=CC=CC=C1 SUIKWZVCSWVADP-UHFFFAOYSA-N 0.000 description 10
230000003389 potentiating effect Effects 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
230000001225 therapeutic effect Effects 0.000 description 9
238000011282 treatment Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
108090000862 Ion Channels Proteins 0.000 description 8
102000004310 Ion Channels Human genes 0.000 description 8
210000004369 blood Anatomy 0.000 description 8
239000008280 blood Substances 0.000 description 8
229940079593 drug Drugs 0.000 description 8
230000003993 interaction Effects 0.000 description 8
238000000746 purification Methods 0.000 description 8
238000004293 19F NMR spectroscopy Methods 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000013459 approach Methods 0.000 description 7
239000013058 crude material Substances 0.000 description 7
230000001965 increasing effect Effects 0.000 description 7
239000000463 material Substances 0.000 description 7
230000036470 plasma concentration Effects 0.000 description 7
239000002904 solvent Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
230000001988 toxicity Effects 0.000 description 7
231100000419 toxicity Toxicity 0.000 description 7
108010010803 Gelatin Proteins 0.000 description 6
239000003429 antifungal agent Substances 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
238000009472 formulation Methods 0.000 description 6
229920000159 gelatin Polymers 0.000 description 6
239000008273 gelatin Substances 0.000 description 6
235000019322 gelatine Nutrition 0.000 description 6
235000011852 gelatine desserts Nutrition 0.000 description 6
238000011534 incubation Methods 0.000 description 6
210000001853 liver microsome Anatomy 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000000047 product Substances 0.000 description 6
102000005702 Calcium-Activated Potassium Channels Human genes 0.000 description 5
108010045489 Calcium-Activated Potassium Channels Proteins 0.000 description 5
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
241000282412 Homo Species 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
108010016797 Sickle Hemoglobin Proteins 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 5
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
239000012346 acetyl chloride Substances 0.000 description 5
239000012267 brine Substances 0.000 description 5
230000001413 cellular effect Effects 0.000 description 5
230000001684 chronic effect Effects 0.000 description 5
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
241000700159 Rattus Species 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000000969 carrier Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
229940125904 compound 1 Drugs 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
230000003834 intracellular effect Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
230000002503 metabolic effect Effects 0.000 description 4
210000001589 microsome Anatomy 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
238000005406 washing Methods 0.000 description 4
AFNXATANNDIXLG-SFHVURJKSA-N 1-[(2r)-2-[(4-chlorophenyl)methylsulfanyl]-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1CS[C@H](C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 AFNXATANNDIXLG-SFHVURJKSA-N 0.000 description 3
LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
101100309447 Caenorhabditis elegans sad-1 gene Proteins 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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
108010054147 Hemoglobins Proteins 0.000 description 3
102000001554 Hemoglobins Human genes 0.000 description 3
206010019851 Hepatotoxicity Diseases 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
229940043379 ammonium hydroxide Drugs 0.000 description 3
238000010171 animal model Methods 0.000 description 3
230000001857 anti-mycotic effect Effects 0.000 description 3
230000008901 benefit Effects 0.000 description 3
238000004166 bioassay Methods 0.000 description 3
HRLJEADIACXJQZ-UHFFFAOYSA-N bis(4-fluorophenyl)-phenylmethanol Chemical compound C=1C=C(F)C=CC=1C(C=1C=CC(F)=CC=1)(O)C1=CC=CC=C1 HRLJEADIACXJQZ-UHFFFAOYSA-N 0.000 description 3
229960005074 butoconazole Drugs 0.000 description 3
SWLMUYACZKCSHZ-UHFFFAOYSA-N butoconazole Chemical compound C1=CC(Cl)=CC=C1CCC(SC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 SWLMUYACZKCSHZ-UHFFFAOYSA-N 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
229940126214 compound 3 Drugs 0.000 description 3
239000008298 dragée Substances 0.000 description 3
229960003913 econazole Drugs 0.000 description 3
230000007686 hepatotoxicity Effects 0.000 description 3
231100000304 hepatotoxicity Toxicity 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
239000012528 membrane Substances 0.000 description 3
230000003228 microsomal effect Effects 0.000 description 3
229960003483 oxiconazole Drugs 0.000 description 3
QRJJEGAJXVEBNE-MOHJPFBDSA-N oxiconazole Chemical compound ClC1=CC(Cl)=CC=C1CO\N=C(C=1C(=CC(Cl)=CC=1)Cl)\CN1C=NC=C1 QRJJEGAJXVEBNE-MOHJPFBDSA-N 0.000 description 3
239000008177 pharmaceutical agent Substances 0.000 description 3
239000002243 precursor Substances 0.000 description 3
230000002035 prolonged effect Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000000523 sample Substances 0.000 description 3
SCTZUZTYRMOMKT-UHFFFAOYSA-N senicapoc Chemical compound C=1C=C(F)C=CC=1C(C=1C=CC(F)=CC=1)(C(=O)N)C1=CC=CC=C1 SCTZUZTYRMOMKT-UHFFFAOYSA-N 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
229960002607 sulconazole Drugs 0.000 description 3
239000003826 tablet Substances 0.000 description 3
LKFIWRPOVFNPKR-UHFFFAOYSA-N (2-fluorophenyl)-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=CC=C1F LKFIWRPOVFNPKR-UHFFFAOYSA-N 0.000 description 2
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
YDUUBPHYBQXQIX-UHFFFAOYSA-N (3-fluorophenyl)-bis(4-fluorophenyl)methanol Chemical compound C=1C=C(F)C=CC=1C(C=1C=C(F)C=CC=1)(O)C1=CC=C(F)C=C1 YDUUBPHYBQXQIX-UHFFFAOYSA-N 0.000 description 2
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
OIIGTIPIURUMQN-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)-2-phenylacetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)(C=1C=CC(F)=CC=1)C1=CC=CC=C1 OIIGTIPIURUMQN-UHFFFAOYSA-N 0.000 description 2
GPZBNFQWFTYNNI-UHFFFAOYSA-N 2-(2-fluorophenyl)-2,2-bis(4-fluorophenyl)acetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)(C=1C(=CC=CC=1)F)C1=CC=C(F)C=C1 GPZBNFQWFTYNNI-UHFFFAOYSA-N 0.000 description 2
PZAMAMVNJOKHHZ-UHFFFAOYSA-N 2-(3-fluorophenyl)-2,2-bis(4-fluorophenyl)acetamide Chemical compound C=1C=C(F)C=CC=1C(C=1C=C(F)C=CC=1)(C(=O)N)C1=CC=C(F)C=C1 PZAMAMVNJOKHHZ-UHFFFAOYSA-N 0.000 description 2
HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 2
JRIDNJRPMHCUMK-UHFFFAOYSA-N 3,3,3-triphenylpropanamide Chemical class C=1C=CC=CC=1C(C=1C=CC=CC=1)(CC(=O)N)C1=CC=CC=C1 JRIDNJRPMHCUMK-UHFFFAOYSA-N 0.000 description 2
HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
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 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
206010022998 Irritability Diseases 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
239000008272 agar Substances 0.000 description 2
235000010419 agar Nutrition 0.000 description 2
229940040563 agaric acid Drugs 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
239000012965 benzophenone Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
230000008859 change Effects 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
238000000576 coating method Methods 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
229940125797 compound 12 Drugs 0.000 description 2
229940126142 compound 16 Drugs 0.000 description 2
229940125810 compound 20 Drugs 0.000 description 2
229940125898 compound 5 Drugs 0.000 description 2
230000001086 cytosolic effect Effects 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
238000006392 deoxygenation reaction Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000010685 fatty oil Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
230000006872 improvement Effects 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
229960002509 miconazole Drugs 0.000 description 2
210000000107 myocyte Anatomy 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
230000000737 periodic effect Effects 0.000 description 2
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
238000006116 polymerization reaction Methods 0.000 description 2
239000000843 powder Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
235000010413 sodium alginate Nutrition 0.000 description 2
239000000661 sodium alginate Substances 0.000 description 2
229940005550 sodium alginate Drugs 0.000 description 2
241000894007 species Species 0.000 description 2
239000007858 starting material Substances 0.000 description 2
125000000547 substituted alkyl group Chemical group 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
238000011830 transgenic mouse model Methods 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
210000003462 vein Anatomy 0.000 description 2
OBUSEBRACGMKSM-UHFFFAOYSA-N (2-fluorophenyl)-(4-fluorophenyl)-phenylmethanol Chemical compound C=1C=C(F)C=CC=1C(C=1C(=CC=CC=1)F)(O)C1=CC=CC=C1 OBUSEBRACGMKSM-UHFFFAOYSA-N 0.000 description 1
BZGCOAGBUWICEM-UHFFFAOYSA-N (2-fluorophenyl)-bis(4-fluorophenyl)methanol Chemical compound C=1C=C(F)C=CC=1C(C=1C(=CC=CC=1)F)(O)C1=CC=C(F)C=C1 BZGCOAGBUWICEM-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
QMDUCVYRINJLBT-UHFFFAOYSA-N 1-[chloro-(2-fluorophenyl)-phenylmethyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1C(Cl)(C=1C(=CC=CC=1)F)C1=CC=CC=C1 QMDUCVYRINJLBT-UHFFFAOYSA-N 0.000 description 1
FYPNFOAHWMDUQH-UHFFFAOYSA-N 1-[chloro-(4-fluorophenyl)-phenylmethyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1C(Cl)(C=1C=CC(F)=CC=1)C1=CC=CC=C1 FYPNFOAHWMDUQH-UHFFFAOYSA-N 0.000 description 1
QLWVQIHBVUMERO-UHFFFAOYSA-N 1-[chloro-bis(4-fluorophenyl)methyl]-3-fluorobenzene Chemical compound C1=CC(F)=CC=C1C(Cl)(C=1C=C(F)C=CC=1)C1=CC=C(F)C=C1 QLWVQIHBVUMERO-UHFFFAOYSA-N 0.000 description 1
QDFKKJYEIFBEFC-UHFFFAOYSA-N 1-bromo-3-fluorobenzene Chemical compound FC1=CC=CC(Br)=C1 QDFKKJYEIFBEFC-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
RNIPJYFZGXJSDD-UHFFFAOYSA-N 2,4,5-triphenyl-1h-imidazole Chemical class C1=CC=CC=C1C1=NC(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N1 RNIPJYFZGXJSDD-UHFFFAOYSA-N 0.000 description 1
VDPKWHHLYDETTO-UHFFFAOYSA-N 2-(2-fluorophenyl)-2,2-bis(4-fluorophenyl)acetamide Chemical compound C=1C=C(F)C=CC=1C(C=1C(=CC=CC=1)F)(C(=O)N)C1=CC=C(F)C=C1 VDPKWHHLYDETTO-UHFFFAOYSA-N 0.000 description 1
UFALWTGZIJAUPP-UHFFFAOYSA-N 2-(2-fluorophenyl)-2-(4-fluorophenyl)-2-phenylacetamide Chemical compound C=1C=C(F)C=CC=1C(C=1C(=CC=CC=1)F)(C(=O)N)C1=CC=CC=C1 UFALWTGZIJAUPP-UHFFFAOYSA-N 0.000 description 1
GCBLBZHTXIQPKL-UHFFFAOYSA-N 2-(2-fluorophenyl)-2-(4-fluorophenyl)-2-phenylacetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)(C=1C(=CC=CC=1)F)C1=CC=CC=C1 GCBLBZHTXIQPKL-UHFFFAOYSA-N 0.000 description 1
MATXILFUWCTUIS-UHFFFAOYSA-N 2-(3-fluorophenyl)-2,2-bis(4-fluorophenyl)acetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)(C=1C=C(F)C=CC=1)C1=CC=C(F)C=C1 MATXILFUWCTUIS-UHFFFAOYSA-N 0.000 description 1
XMGJGSKRRWXOIF-UHFFFAOYSA-N 2-(azepan-1-yl)ethyl 2-cyclohexyl-2-thiophen-3-ylacetate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1CCCCC1C(C1=CSC=C1)C(=O)OCCN1CCCCCC1 XMGJGSKRRWXOIF-UHFFFAOYSA-N 0.000 description 1
YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 1
LSQARZALBDFYQZ-UHFFFAOYSA-N 4,4'-difluorobenzophenone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 LSQARZALBDFYQZ-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
101150065749 Churc1 gene Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
241000792859 Enema Species 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000003951 Erythropoietin Human genes 0.000 description 1
108090000394 Erythropoietin Proteins 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
206010053317 Hydrophobia Diseases 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 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
102000007008 Intermediate-Conductance Calcium-Activated Potassium Channels Human genes 0.000 description 1
108010033149 Intermediate-Conductance Calcium-Activated Potassium Channels Proteins 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
229930191564 Monensin Natural products 0.000 description 1
GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
206010040642 Sickle cell anaemia with crisis Diseases 0.000 description 1
229920002125 Sokalan® Polymers 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
206010042434 Sudden death Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
206010053648 Vascular occlusion Diseases 0.000 description 1
GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
102000002852 Vasopressins Human genes 0.000 description 1
108010004977 Vasopressins Proteins 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
150000003869 acetamides Chemical class 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
150000001243 acetic acids Chemical class 0.000 description 1
230000002411 adverse Effects 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000002543 antimycotic Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
235000014121 butter Nutrition 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000003710 calcium ionophore Substances 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
239000001569 carbon dioxide Substances 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229960004485 cetiedil citrate Drugs 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000000470 constituent Substances 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000007423 decrease Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000000378 dietary effect Effects 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
229940105423 erythropoietin Drugs 0.000 description 1
CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
210000003608 fece Anatomy 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
125000004407 fluoroaryl group Chemical group 0.000 description 1
230000037406 food intake Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
229940014259 gelatin Drugs 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000001788 irregular Effects 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
230000002934 lysing effect Effects 0.000 description 1
BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229960005358 monensin Drugs 0.000 description 1
GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
229960001476 pentoxifylline Drugs 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
150000003109 potassium Chemical class 0.000 description 1
229940037179 potassium ion Drugs 0.000 description 1
229910001414 potassium ion Inorganic materials 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
239000003755 preservative agent Substances 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
230000000069 prophylactic effect Effects 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000004904 shortening Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000008685 targeting Effects 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
150000003852 triazoles Chemical class 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
OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
239000004474 valine Substances 0.000 description 1
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
208000021331 vascular occlusion disease Diseases 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
208000003663 ventricular fibrillation Diseases 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

OA1200100220A 1999-02-23 2000-02-10 Gardos channel antagonists. OA11838A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US13551199P	1999-02-23	1999-02-23
US09/386,601 US6288122B1 (en)	1999-02-23	1999-08-31	Gardos channel antagonists

Publications (1)

Publication Number	Publication Date
OA11838A true OA11838A (en)	2005-08-22

Family

ID=26833406

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200100220A OA11838A (en)	1999-02-23	2000-02-10	Gardos channel antagonists.

Country Status (16)

Country	Link
US (1)	US6288122B1 (de)
EP (1)	EP1158971B1 (de)
JP (2)	JP4038337B2 (de)
KR (1)	KR100705726B1 (de)
CN (1)	CN1193748C (de)
AP (1)	AP1465A (de)
AT (1)	ATE370728T1 (de)
AU (1)	AU762039B2 (de)
BR (1)	BR0008416A (de)
CA (1)	CA2371857C (de)
DE (1)	DE60036093T2 (de)
ES (1)	ES2291191T3 (de)
HK (1)	HK1045262B (de)
IL (2)	IL145012A0 (de)
OA (1)	OA11838A (de)
WO (1)	WO2000050026A1 (de)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2003004010A1 (en) *	2001-07-06	2003-01-16	Poseidon Pharmaceuticals A/S	Carbonylamino derivatives useful for obtaining immune regulation
DE60322019D1 (de) *	2002-01-04	2008-08-21	Neurosearch As	Kaliumkanal-modulatoren
AU2003217810C9 (en) *	2002-02-28	2008-06-12	Icagen, Inc.	Methods for treating diseases related to intraocular pressure
US20070027205A1 (en) *	2003-07-03	2007-02-01	Joachim Demnitz	Diarylmethyl derivatives as potassium channel modulators
WO2005003143A1 (en) *	2003-07-03	2005-01-13	Poseidon Pharmaceuticals A/S	Novel potassium channel modulators
AU2006210641A1 (en) *	2005-02-01	2006-08-10	Icagen, Inc.	Imines as ion channel modulators
US20100056637A1 (en) *	2005-12-20	2010-03-04	Icagen, Inc.	Treatment methods using triaryl methane compounds
WO2007075849A2 (en) *	2005-12-20	2007-07-05	Icagen, Inc.	Treatment methods using triaryl methane compounds
WO2009027292A1 (en) *	2007-08-24	2009-03-05	Neurosearch A/S	Carbonylamino derivatives useful for the treatment of certain inflammatory disorders
US20090076157A1 (en) *	2007-09-15	2009-03-19	Protia, Llc	Deuterium-enriched senicapoc
SG189745A1 (en)	2008-04-09	2013-05-31	Cerus Corp	Improved quenching methods for red blood cell pathogen inactivation
CA2742610A1 (en)	2008-11-10	2010-05-14	Jun Li	Compositions and methods for modulating cell-cell fusion via intermediate-conductance calcium-activated potassium channels
US10179115B2 (en)	2015-02-20	2019-01-15	The Children's Medical Center Corporation	Methods for treating malaria using potassium channel inhibitors
EP3106155A1 (de) *	2015-06-15	2016-12-21	Universite d'Aix Marseille	Behandlung und diagnose der erblichen xerokytose
CA3076520A1 (en) *	2016-10-25	2018-05-03	Paracelsus Neuroscience I, LLC	Use of senicapoc for treatment of neuropathic pain
WO2018162426A1 (en)	2017-03-06	2018-09-13	INSERM (Institut National de la Santé et de la Recherche Médicale)	Treatment and diagnosis of hereditary xerocytosis
WO2020198939A1 (zh)	2019-03-29	2020-10-08	深圳仁泰医药科技有限公司	2,2-双(4-氟苯基)-2-苯乙酰胺的晶型a及其制备方法和应用
US12186286B2 (en) *	2019-07-29	2025-01-07	Paracelsus Neuroscience Llc	Use of senicapoc for treatment of stroke
EP4181908A4 (de) *	2020-07-14	2024-03-06	Adimabio LLC	Zusammensetzungen mit gardos-kanalantagonisten und deren verwendungen
EP4259130B1 (de)	2020-12-11	2026-03-04	Sanquin IP B.V.	Gardos-kanalhemmer oder andere mittel zur verwendung bei der behandlung und prävention von anämie bei chronischer erkrankung

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5273992A (en)	1992-11-02	1993-12-28	Beth Israel Hospital Assoc. Inc.	Method for reducing sickle erythrocyte dehydration and delaying the occurrence of erythrocyte sickling in-situ
WO1997034589A1 (en)	1996-03-20	1997-09-25	President And Fellows Of Harvard College	Triaryl methane compounds for sickle cell disease

1999
- 1999-08-31 US US09/386,601 patent/US6288122B1/en not_active Expired - Lifetime
2000
- 2000-02-10 CA CA002371857A patent/CA2371857C/en not_active Expired - Fee Related
- 2000-02-10 EP EP00907283A patent/EP1158971B1/de not_active Expired - Lifetime
- 2000-02-10 JP JP2000600638A patent/JP4038337B2/ja not_active Expired - Fee Related
- 2000-02-10 ES ES00907283T patent/ES2291191T3/es not_active Expired - Lifetime
- 2000-02-10 WO PCT/US2000/003663 patent/WO2000050026A1/en not_active Ceased
- 2000-02-10 DE DE60036093T patent/DE60036093T2/de not_active Expired - Lifetime
- 2000-02-10 AP APAP/P/2001/002268A patent/AP1465A/en active
- 2000-02-10 AT AT00907283T patent/ATE370728T1/de active
- 2000-02-10 KR KR1020017010707A patent/KR100705726B1/ko not_active Expired - Fee Related
- 2000-02-10 AU AU28807/00A patent/AU762039B2/en not_active Ceased
- 2000-02-10 HK HK02106773.8A patent/HK1045262B/zh not_active IP Right Cessation
- 2000-02-10 IL IL14501200A patent/IL145012A0/xx active IP Right Grant
- 2000-02-10 OA OA1200100220A patent/OA11838A/en unknown
- 2000-02-10 CN CNB008054525A patent/CN1193748C/zh not_active Expired - Fee Related
- 2000-02-10 BR BR0008416-6A patent/BR0008416A/pt not_active IP Right Cessation
2001
- 2001-08-21 IL IL145012A patent/IL145012A/en not_active IP Right Cessation
2007
- 2007-05-02 JP JP2007121967A patent/JP2007262075A/ja active Pending

Also Published As

Publication number	Publication date
JP2007262075A (ja)	2007-10-11
DE60036093D1 (de)	2007-10-04
JP4038337B2 (ja)	2008-01-23
HK1045262B (zh)	2005-07-29
WO2000050026A1 (en)	2000-08-31
CA2371857C (en)	2008-07-29
DE60036093T2 (de)	2008-05-15
EP1158971A1 (de)	2001-12-05
EP1158971B1 (de)	2007-08-22
AP2001002268A0 (en)	2001-09-30
BR0008416A (pt)	2002-01-29
CA2371857A1 (en)	2000-08-31
AU2880700A (en)	2000-09-14
CN1193748C (zh)	2005-03-23
KR20020002393A (ko)	2002-01-09
ATE370728T1 (de)	2007-09-15
AU762039B2 (en)	2003-06-19
ES2291191T3 (es)	2008-03-01
HK1045262A1 (en)	2002-11-22
CN1344158A (zh)	2002-04-10
EP1158971A4 (de)	2003-04-16
US6288122B1 (en)	2001-09-11
JP2002537331A (ja)	2002-11-05
IL145012A (en)	2006-12-10
KR100705726B1 (ko)	2007-04-11
AP1465A (en)	2005-09-22
IL145012A0 (en)	2002-06-30

Publication	Publication Date	Title
US6288122B1 (en)	2001-09-11	Gardos channel antagonists
BR9908084B1 (pt)	2009-12-01	composto 2-fenil-1-(3,4-diidróxi-5-nitrofenil)-1-etanona, composição farmacêutica, e, uso de um composto.
US20100056637A1 (en)	2010-03-04	Treatment methods using triaryl methane compounds
JPH04270261A (ja)	1992-09-25	イソプレノイドホスホリパーゼ▲ａ２▼阻害剤およびそれを包含する製剤
US4094908A (en)	1978-06-13	Alpha-substituted benzhydrol derivatives
JP2009545549A (ja)	2009-12-24	Ｃｐｔ阻害剤としての４−トリメチルアンモニウム−３−アミノブチレートおよび４−トリメチルフォスフォニウム−３−アミノブチレート誘導体
JPS61218570A (ja)	1986-09-29	新規複素環アミド化合物、およびそれらを含有する医薬組成物
US4797391A (en)	1989-01-10	((5,6-dichloro-3-oxo-9,9a-disubstituted-2,3,9,9a-tetrahydrofluoren-7-yl)oxy)alkanoic acids and alkanimidamides
CS267551B1 (en)	1990-02-12	Pharmaceutical agents for asthma treatment and method of effective substance production
US4835313A (en)	1989-05-30	(5,6-dichloro-3-oxo-9α-propyl-2,3,9,9α-tetrahydrofluoren-7-yl) alkanimidamides
KR20250004056A (ko)	2025-01-07	케어바스틴 염 및 그의 용도
US20240350448A1 (en)	2024-10-24	Dichloroacetic acid conjugating diphenyl ethane compound, and preparation method and application thereof
US4562206A (en)	1985-12-31	Orally effective inotropic compounds
US3856951A (en)	1974-12-24	Substituted benzoic acid hypoliphemic agents
ZA200106847B (en)	2002-08-20	Gardos channel antagonists.
JPS6330283B2 (de)	1988-06-17
US3457354A (en)	1969-07-22	Treatment of hypertension with 2-hydroxy (or amino) - 4,5 - dihydroxyphenethylamine derivatives
US12194029B1 (en)	2025-01-14	Ethyl-1-(substitutedbenzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates as anticancer agents
US20260001833A1 (en)	2026-01-01	Compounds, compositions, and methods for reducing production of trimethylamine
AU2006320567A1 (en)	2007-06-07	Inhibitors of kynurenine aminotransferase and uses therefor
US20060100289A1 (en)	2006-05-11	Nitrone compounds, pharmaceutical compositions containing the same and methods for treating inflammation and neuropathic pain
US4146728A (en)	1979-03-27	Esters of 2-[4-(4-chlorobenzoyl)-phenoxy-2-methyl-propionic acid with bis-(hydroxyalkylthio)-alkanes
US3740395A (en)	1973-06-19	Ethyl 10 - (beta-morpholylpropionyl)-phenthiazine-2-carbamate hydrochloride
US3673197A (en)	1972-06-27	Exo-dibicycloalkane carboxamides
JPH0374673B2 (de)	1991-11-27