NO316171B1 - Arylkarboksylsyre- og tetrazolderivater, farmasöytisk preparat samt fremgangsmåte for fremstilling og anvendelse derav - Google Patents

Arylkarboksylsyre- og tetrazolderivater, farmasöytisk preparat samt fremgangsmåte for fremstilling og anvendelse derav Download PDF

Info

Publication number: NO316171B1
Authority: NO; Norway
Prior art keywords: acetic acid; compound according; compound; acid; mmol
Prior art date: 1998-12-23

Application number

NO19996366A

Other languages

English (en)

Norwegian (no)

Other versions

NO996366L (no

NO996366D0 (no

Inventor

Francisco Javier Lopez-Tapia

Alexander Victor Muehldorf

Counde O'yang

Daniel Lee Severance

Original Assignee

Hoffmann La Roche

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.)

1998-12-23

Filing date

1999-12-21

Publication date

2003-12-22

1999-12-21 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1999-12-21 Publication of NO996366D0 publication Critical patent/NO996366D0/no

2000-06-26 Publication of NO996366L publication Critical patent/NO996366L/no

2003-12-22 Publication of NO316171B1 publication Critical patent/NO316171B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 85
238000000034 method Methods 0.000 title claims description 40
239000000825 pharmaceutical preparation Substances 0.000 title claims description 16
-1 Aryl Carboxylic Acid Chemical class 0.000 title description 59
150000003536 tetrazoles Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 190
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 123
239000000203 mixture Substances 0.000 claims description 99
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
201000010099 disease Diseases 0.000 claims description 40
238000006243 chemical reaction Methods 0.000 claims description 36
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 30
108091006335 Prostaglandin I receptors Proteins 0.000 claims description 29
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
125000002947 alkylene group Chemical group 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 14
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
229910052794 bromium Inorganic materials 0.000 claims description 14
239000012453 solvate Substances 0.000 claims description 13
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 11
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
125000004450 alkenylene group Chemical group 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 9
206010020772 Hypertension Diseases 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
206010022562 Intermittent claudication Diseases 0.000 claims description 6
208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 6
208000021328 arterial occlusion Diseases 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
230000002496 gastric effect Effects 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
235000019260 propionic acid Nutrition 0.000 claims description 6
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 6
208000037803 restenosis Diseases 0.000 claims description 6
VCTVPGPDKHRWMQ-UHFFFAOYSA-N 2-[3-[3-(diphenylcarbamoyloxy)propyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 VCTVPGPDKHRWMQ-UHFFFAOYSA-N 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 5
208000005171 Dysmenorrhea Diseases 0.000 claims description 5
206010028851 Necrosis Diseases 0.000 claims description 5
206010036600 Premature labour Diseases 0.000 claims description 5
208000025865 Ulcer Diseases 0.000 claims description 5
230000001154 acute effect Effects 0.000 claims description 5
208000021156 intermittent vascular claudication Diseases 0.000 claims description 5
230000017074 necrotic cell death Effects 0.000 claims description 5
210000000440 neutrophil Anatomy 0.000 claims description 5
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 5
230000036269 ulceration Effects 0.000 claims description 5
230000029663 wound healing Effects 0.000 claims description 5
208000031104 Arterial Occlusive disease Diseases 0.000 claims description 4
208000008967 Enuresis Diseases 0.000 claims description 4
208000004880 Polyuria Diseases 0.000 claims description 4
201000001880 Sexual dysfunction Diseases 0.000 claims description 4
206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 4
208000007536 Thrombosis Diseases 0.000 claims description 4
238000002399 angioplasty Methods 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
230000035619 diuresis Effects 0.000 claims description 4
125000001188 haloalkyl group Chemical group 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
208000005346 nocturnal enuresis Diseases 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
229940075993 receptor modulator Drugs 0.000 claims description 4
230000000306 recurrent effect Effects 0.000 claims description 4
231100000872 sexual dysfunction Toxicity 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
206010030043 Ocular hypertension Diseases 0.000 claims description 3
206010034576 Peripheral ischaemia Diseases 0.000 claims description 3
208000001647 Renal Insufficiency Diseases 0.000 claims description 3
208000009205 Tinnitus Diseases 0.000 claims description 3
208000029078 coronary artery disease Diseases 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
230000007365 immunoregulation Effects 0.000 claims description 3
201000006370 kidney failure Diseases 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
201000005060 thrombophlebitis Diseases 0.000 claims description 3
231100000886 tinnitus Toxicity 0.000 claims description 3
208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
125000000623 heterocyclic group Chemical group 0.000 claims 2
125000000753 cycloalkyl group Chemical group 0.000 claims 1
125000001072 heteroaryl group Chemical group 0.000 claims 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
208000011580 syndromic disease Diseases 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 94
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
239000000243 solution Substances 0.000 description 78
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 45
239000007787 solid Substances 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
238000000746 purification Methods 0.000 description 27
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
239000002904 solvent Substances 0.000 description 23
239000000284 extract Substances 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 21
229910052938 sodium sulfate Inorganic materials 0.000 description 20
235000011152 sodium sulphate Nutrition 0.000 description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000002253 acid Substances 0.000 description 18
238000004458 analytical method Methods 0.000 description 16
238000003556 assay Methods 0.000 description 16
239000012267 brine Substances 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000003960 organic solvent Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
239000000843 powder Substances 0.000 description 13
239000010410 layer Substances 0.000 description 12
239000012299 nitrogen atmosphere Substances 0.000 description 12
239000000047 product Substances 0.000 description 12
239000000018 receptor agonist Substances 0.000 description 12
229940044601 receptor agonist Drugs 0.000 description 12
238000003756 stirring Methods 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
239000004480 active ingredient Substances 0.000 description 11
239000002775 capsule Substances 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
239000000725 suspension Substances 0.000 description 11
239000003826 tablet Substances 0.000 description 11
WHNQTHDJEZTVHS-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(CCC(=O)O)=NC2=C1 WHNQTHDJEZTVHS-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
239000012300 argon atmosphere Substances 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
239000003153 chemical reaction reagent Substances 0.000 description 9
XNBKKRFABABBPM-UHFFFAOYSA-N n,n-diphenylcarbamoyl chloride Chemical compound C=1C=CC=CC=1N(C(=O)Cl)C1=CC=CC=C1 XNBKKRFABABBPM-UHFFFAOYSA-N 0.000 description 9
238000012360 testing method Methods 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 8
239000000872 buffer Substances 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
210000004978 chinese hamster ovary cell Anatomy 0.000 description 8
238000009472 formulation Methods 0.000 description 8
239000004615 ingredient Substances 0.000 description 8
230000000144 pharmacologic effect Effects 0.000 description 8
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 8
238000010898 silica gel chromatography Methods 0.000 description 8
239000007858 starting material Substances 0.000 description 8
241000282472 Canis lupus familiaris Species 0.000 description 7
101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
239000007788 liquid Substances 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
235000011181 potassium carbonates Nutrition 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
239000000126 substance Substances 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
SJBPKKHVNARAAG-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)-2-methylphenoxy]acetic acid Chemical compound C1=CC=C(OCC(O)=O)C(C)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 SJBPKKHVNARAAG-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
239000002168 alkylating agent Substances 0.000 description 6
229940100198 alkylating agent Drugs 0.000 description 6
239000000010 aprotic solvent Substances 0.000 description 6
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
238000007796 conventional method Methods 0.000 description 6
239000013078 crystal Substances 0.000 description 6
239000002552 dosage form Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
238000010992 reflux Methods 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
235000011121 sodium hydroxide Nutrition 0.000 description 6
238000001356 surgical procedure Methods 0.000 description 6
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 6
241000124008 Mammalia Species 0.000 description 5
241000700159 Rattus Species 0.000 description 5
101000874172 Rattus norvegicus Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial Proteins 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000002152 alkylating effect Effects 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000007921 spray Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
QWFILMGCTBJAQQ-UHFFFAOYSA-N 3-(hydroxymethyl)-2-methylphenol Chemical compound CC1=C(O)C=CC=C1CO QWFILMGCTBJAQQ-UHFFFAOYSA-N 0.000 description 4
RIERSGULWXEJKL-UHFFFAOYSA-N 3-hydroxy-2-methylbenzoic acid Chemical compound CC1=C(O)C=CC=C1C(O)=O RIERSGULWXEJKL-UHFFFAOYSA-N 0.000 description 4
IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 4
239000005711 Benzoic acid Substances 0.000 description 4
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
125000003158 alcohol group Chemical group 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
235000010233 benzoic acid Nutrition 0.000 description 4
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
230000017531 blood circulation Effects 0.000 description 4
229910000085 borane Inorganic materials 0.000 description 4
230000001593 cAMP accumulation Effects 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
229910002092 carbon dioxide Inorganic materials 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
238000010531 catalytic reduction reaction Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
239000012467 final product Substances 0.000 description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
239000007937 lozenge Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
PKALKWFZXXGNJD-AATRIKPKSA-N methyl (2E)-3-(3-hydroxyphenyl)acrylate Chemical compound COC(=O)\C=C\C1=CC=CC(O)=C1 PKALKWFZXXGNJD-AATRIKPKSA-N 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
230000002285 radioactive effect Effects 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000003381 stabilizer Substances 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 4
239000002562 thickening agent Substances 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
GTXIBCRXNKXKCF-UHFFFAOYSA-N 2-(2,3-dimethoxyphenyl)-4,4-dimethyl-5h-1,3-oxazole Chemical compound COC1=CC=CC(C=2OCC(C)(C)N=2)=C1OC GTXIBCRXNKXKCF-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
GMGJNCIPLIGDAZ-UHFFFAOYSA-N 2-[2-chloro-3-(diphenylcarbamoyloxymethyl)phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(COC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1Cl GMGJNCIPLIGDAZ-UHFFFAOYSA-N 0.000 description 3
CXJSCJZRBBGWTK-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(COC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 CXJSCJZRBBGWTK-UHFFFAOYSA-N 0.000 description 3
DUUOGIKAXBFCHN-UHFFFAOYSA-N 2-[3-(hydroxymethyl)-2-methylphenoxy]acetic acid Chemical compound CC1=C(CO)C=CC=C1OCC(O)=O DUUOGIKAXBFCHN-UHFFFAOYSA-N 0.000 description 3
WWCDWZNVGWYTRE-CSKARUKUSA-N 2-[3-[(e)-3-(diphenylcarbamoyloxy)prop-1-enyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(\C=C\COC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 WWCDWZNVGWYTRE-CSKARUKUSA-N 0.000 description 3
VFCYCVIHXKLLNX-UHFFFAOYSA-N 2-chloro-3-(hydroxymethyl)phenol Chemical compound OCC1=CC=CC(O)=C1Cl VFCYCVIHXKLLNX-UHFFFAOYSA-N 0.000 description 3
TVQDIGAZKJXXLX-UHFFFAOYSA-N 3-(3-hydroxypropyl)phenol Chemical compound OCCCC1=CC=CC(O)=C1 TVQDIGAZKJXXLX-UHFFFAOYSA-N 0.000 description 3
WPDXAMRGYMDTOV-UHFFFAOYSA-N 3-bromo-2-methylphenol Chemical compound CC1=C(O)C=CC=C1Br WPDXAMRGYMDTOV-UHFFFAOYSA-N 0.000 description 3
SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 3
MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 3
241000220479 Acacia Species 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
206010003210 Arteriosclerosis Diseases 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
235000010643 Leucaena leucocephala Nutrition 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
208000003782 Raynaud disease Diseases 0.000 description 3
208000012322 Raynaud phenomenon Diseases 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 3
IMNITRYEZDZJLN-UHFFFAOYSA-N acetic acid;2-methylpropan-2-amine Chemical compound CC([O-])=O.CC(C)(C)[NH3+] IMNITRYEZDZJLN-UHFFFAOYSA-N 0.000 description 3
SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
239000007900 aqueous suspension Substances 0.000 description 3
208000011775 arteriosclerosis disease Diseases 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
229910000024 caesium carbonate Inorganic materials 0.000 description 3
239000001569 carbon dioxide Substances 0.000 description 3
208000026106 cerebrovascular disease Diseases 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000003086 colorant Substances 0.000 description 3
239000006071 cream Substances 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
238000001514 detection method Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000002270 dispersing agent Substances 0.000 description 3
238000011833 dog model Methods 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
239000012091 fetal bovine serum Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
239000011981 lindlar catalyst Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
AYMQCLGUHSIDFY-UHFFFAOYSA-N methyl 2-(3-formylphenoxy)acetate Chemical compound COC(=O)COC1=CC=CC(C=O)=C1 AYMQCLGUHSIDFY-UHFFFAOYSA-N 0.000 description 3
GDRYLEUFAQNLKJ-UHFFFAOYSA-N methyl 2-[2-chloro-3-(hydroxymethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(CO)=C1Cl GDRYLEUFAQNLKJ-UHFFFAOYSA-N 0.000 description 3
PXGGYWKCASWNEC-UHFFFAOYSA-N methyl 2-[3-(hydroxymethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(CO)=C1 PXGGYWKCASWNEC-UHFFFAOYSA-N 0.000 description 3
IIFOKIAATXLZIB-UHFFFAOYSA-N methyl 3-(3-hydroxyphenyl)propanoate Chemical compound COC(=O)CCC1=CC=CC(O)=C1 IIFOKIAATXLZIB-UHFFFAOYSA-N 0.000 description 3
ZKHLDHPVVPPVSA-UHFFFAOYSA-N methyl 4-(3-bromophenyl)butanoate Chemical compound COC(=O)CCCC1=CC=CC(Br)=C1 ZKHLDHPVVPPVSA-UHFFFAOYSA-N 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
208000031225 myocardial ischemia Diseases 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
239000008188 pellet Substances 0.000 description 3
150000002989 phenols Chemical class 0.000 description 3
XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
230000002265 prevention Effects 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000829 suppository Substances 0.000 description 3
FOQSBTPHWBIURQ-UHFFFAOYSA-N tert-butyl 2-[3-(3-hydroxyprop-1-ynyl)-2-methylphenoxy]acetate Chemical compound CC1=C(OCC(=O)OC(C)(C)C)C=CC=C1C#CCO FOQSBTPHWBIURQ-UHFFFAOYSA-N 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
239000011534 wash buffer Substances 0.000 description 3
YEMUSDCFQUBPAL-SNAWJCMRSA-N (e)-3-(3-bromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(Br)=C1 YEMUSDCFQUBPAL-SNAWJCMRSA-N 0.000 description 2
JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 2
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
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 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
ZBSGNEYIENETRW-UHFFFAOYSA-N 2,3-bis(hydroxymethyl)phenol Chemical compound OCC1=CC=CC(O)=C1CO ZBSGNEYIENETRW-UHFFFAOYSA-N 0.000 description 2
BADFPGDROOJUPA-UHFFFAOYSA-N 2-(3-bromo-2-methylphenoxy)acetic acid Chemical compound CC1=C(Br)C=CC=C1OCC(O)=O BADFPGDROOJUPA-UHFFFAOYSA-N 0.000 description 2
CRKQPDCSWOJBJY-UHFFFAOYSA-N 2-(3-bromophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=CC(Br)=C1 CRKQPDCSWOJBJY-UHFFFAOYSA-N 0.000 description 2
KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 2
ZLQWQWRPBWZVMT-UHFFFAOYSA-N 2-(3-formyl-2-methylphenoxy)acetic acid Chemical compound CC1=C(OCC(O)=O)C=CC=C1C=O ZLQWQWRPBWZVMT-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
HMEJVKGZESKXFC-UHFFFAOYSA-N 2-chloro-3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1Cl HMEJVKGZESKXFC-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
DSUYDXCCZCHMQF-UHFFFAOYSA-N 3-hydroxy-2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1C1=CC=CC=C1 DSUYDXCCZCHMQF-UHFFFAOYSA-N 0.000 description 2
JLNDMDZMWLVUGD-UHFFFAOYSA-N 3-hydroxy-2-propan-2-ylbenzoic acid Chemical compound CC(C)C1=C(O)C=CC=C1C(O)=O JLNDMDZMWLVUGD-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
MJSLVHKDBWJPCL-UHFFFAOYSA-N 4-(3-bromophenyl)butanoic acid Chemical compound OC(=O)CCCC1=CC=CC(Br)=C1 MJSLVHKDBWJPCL-UHFFFAOYSA-N 0.000 description 2
CCTOEAMRIIXGDJ-UHFFFAOYSA-N 4-hydroxy-2-benzofuran-1,3-dione Chemical compound OC1=CC=CC2=C1C(=O)OC2=O CCTOEAMRIIXGDJ-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
206010048768 Dermatosis Diseases 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
238000006052 Horner reaction Methods 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
208000002193 Pain Diseases 0.000 description 2
208000018262 Peripheral vascular disease Diseases 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
241000112708 Vates Species 0.000 description 2
238000007239 Wittig reaction Methods 0.000 description 2
FYGNJYLXDRROPN-UHFFFAOYSA-N [2-(4-phenylmethoxyphenyl)-1,3-thiazol-4-yl]methanamine Chemical compound NCC1=CSC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=N1 FYGNJYLXDRROPN-UHFFFAOYSA-N 0.000 description 2
238000002679 ablation Methods 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
102000030621 adenylate cyclase Human genes 0.000 description 2
108060000200 adenylate cyclase Proteins 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000000556 agonist Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
125000003172 aldehyde group Chemical group 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
VMWZRHGIAVCFNS-UHFFFAOYSA-J aluminum;lithium;tetrahydroxide Chemical compound [Li+].[OH-].[OH-].[OH-].[OH-].[Al+3] VMWZRHGIAVCFNS-UHFFFAOYSA-J 0.000 description 2
238000010171 animal model Methods 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000008365 aqueous carrier Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000012131 assay buffer Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
210000000748 cardiovascular system Anatomy 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000006285 cell suspension Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
229940125773 compound 10 Drugs 0.000 description 2
229910052802 copper Inorganic materials 0.000 description 2
239000010949 copper Substances 0.000 description 2
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
230000008021 deposition Effects 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
229960001123 epoprostenol Drugs 0.000 description 2
XRFKYWINTGMGLW-UHFFFAOYSA-N ethyl 3-methoxy-2-phenylbenzoate Chemical compound CCOC(=O)C1=CC=CC(OC)=C1C1=CC=CC=C1 XRFKYWINTGMGLW-UHFFFAOYSA-N 0.000 description 2
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
239000006260 foam Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
230000036541 health Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000005556 hormone Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000003993 interaction Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
208000017169 kidney disease Diseases 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
239000006210 lotion Substances 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
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
239000012528 membrane Substances 0.000 description 2
229910021645 metal ion Inorganic materials 0.000 description 2
CYCPWQBUGLSXJZ-UHFFFAOYSA-N methyl 2-[2-chloro-3-(diphenylcarbamoyloxymethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(COC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1Cl CYCPWQBUGLSXJZ-UHFFFAOYSA-N 0.000 description 2
KMHMJTZCPGLMNT-UHFFFAOYSA-N methyl 2-[3-(diphenylcarbamoyloxymethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC(COC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 KMHMJTZCPGLMNT-UHFFFAOYSA-N 0.000 description 2
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
210000003928 nasal cavity Anatomy 0.000 description 2
239000007922 nasal spray Substances 0.000 description 2
229940097496 nasal spray Drugs 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
239000002674 ointment Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
239000002245 particle Substances 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
150000004714 phosphonium salts Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
239000000700 radioactive tracer Substances 0.000 description 2
239000002287 radioligand Substances 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
230000007017 scission Effects 0.000 description 2
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
208000017520 skin disease Diseases 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
WRELEUGQBWXAPV-UHFFFAOYSA-N tert-butyl 2-[3-(1-hydroxyethyl)-2-methylphenoxy]acetate Chemical compound CC(O)C1=CC=CC(OCC(=O)OC(C)(C)C)=C1C WRELEUGQBWXAPV-UHFFFAOYSA-N 0.000 description 2
QZVOEJJVGJOKDJ-UHFFFAOYSA-N tert-butyl 2-[3-(3-hydroxyprop-1-ynyl)phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=CC(C#CCO)=C1 QZVOEJJVGJOKDJ-UHFFFAOYSA-N 0.000 description 2
NCAMUWMBMBDPNN-UHFFFAOYSA-N tert-butyl 2-[3-(diphenylcarbamoyloxymethyl)-2-methylphenoxy]acetate Chemical compound C1=CC=C(OCC(=O)OC(C)(C)C)C(C)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 NCAMUWMBMBDPNN-UHFFFAOYSA-N 0.000 description 2
LKIJFOYYOPQVPQ-UHFFFAOYSA-N tert-butyl 2-[3-(hydroxymethyl)-2-methylphenoxy]acetate Chemical compound CC1=C(CO)C=CC=C1OCC(=O)OC(C)(C)C LKIJFOYYOPQVPQ-UHFFFAOYSA-N 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-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
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
239000008215 water for injection Substances 0.000 description 2
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
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 1
KWMLJOLKUYYJFJ-GASJEMHNSA-N (2xi)-D-gluco-heptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C(O)=O KWMLJOLKUYYJFJ-GASJEMHNSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
ZVCPCZRXWGOICC-UHFFFAOYSA-N 1h-benzo[7]annulene Chemical class C1=CC=CC=C2CC=CC=C21 ZVCPCZRXWGOICC-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
BTHTUOKPKHYQFC-UHFFFAOYSA-N 2-(3-methoxy-2-propan-2-ylphenyl)-4,4-dimethyl-5h-1,3-oxazole Chemical compound COC1=CC=CC(C=2OCC(C)(C)N=2)=C1C(C)C BTHTUOKPKHYQFC-UHFFFAOYSA-N 0.000 description 1
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical group C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
RCMAKYLCUAZCEW-UHFFFAOYSA-N 2-[2-(phenylcarbamoyl)phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC=C1C(=O)NC1=CC=CC=C1 RCMAKYLCUAZCEW-UHFFFAOYSA-N 0.000 description 1
ABVUOKJKELBEEL-UHFFFAOYSA-N 2-[2-methyl-3-[[phenyl(pyridin-3-yl)carbamoyl]oxymethyl]phenoxy]acetic acid Chemical compound C1=CC=C(OCC(O)=O)C(C)=C1COC(=O)N(C=1C=NC=CC=1)C1=CC=CC=C1 ABVUOKJKELBEEL-UHFFFAOYSA-N 0.000 description 1
NGYPYWBOZJTBRJ-UHFFFAOYSA-N 2-[3-(1-hydroxyethyl)-2-methylphenoxy]acetic acid Chemical compound CC(O)C1=CC=CC(OCC(O)=O)=C1C NGYPYWBOZJTBRJ-UHFFFAOYSA-N 0.000 description 1
RBYTVMPCSICCPO-UHFFFAOYSA-N 2-[3-(3-hydroxyprop-1-ynyl)-2-methylphenoxy]acetic acid Chemical compound CC1=C(OCC(O)=O)C=CC=C1C#CCO RBYTVMPCSICCPO-UHFFFAOYSA-N 0.000 description 1
UTFNPDFGXZAIOJ-UHFFFAOYSA-N 2-[3-(3-hydroxyprop-1-ynyl)phenoxy]acetic acid Chemical compound OCC#CC1=CC=CC(OCC(O)=O)=C1 UTFNPDFGXZAIOJ-UHFFFAOYSA-N 0.000 description 1
SRUZQQJWPBXJLM-UHFFFAOYSA-N 2-[3-(3-hydroxypropyl)phenoxy]acetic acid Chemical compound OCCCC1=CC=CC(OCC(O)=O)=C1 SRUZQQJWPBXJLM-UHFFFAOYSA-N 0.000 description 1
DXRAZOBPXVPGDD-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)-2,6-dimethylphenoxy]acetic acid Chemical compound CC1=C(OCC(O)=O)C(C)=CC=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 DXRAZOBPXVPGDD-UHFFFAOYSA-N 0.000 description 1
ZNYGBXZAVAWDPE-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)-2-(hydroxymethyl)phenoxy]acetic acid Chemical compound C1=CC=C(OCC(O)=O)C(CO)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 ZNYGBXZAVAWDPE-UHFFFAOYSA-N 0.000 description 1
IDFLPYPBCYQEQX-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)-2-phenylphenoxy]acetic acid Chemical compound C=1C=CC=CC=1C=1C(OCC(=O)O)=CC=CC=1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 IDFLPYPBCYQEQX-UHFFFAOYSA-N 0.000 description 1
PXDLFMATYHFUEO-UHFFFAOYSA-N 2-[3-(diphenylcarbamoyloxymethyl)-2-propylphenoxy]acetic acid Chemical compound C1=CC=C(OCC(O)=O)C(CCC)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 PXDLFMATYHFUEO-UHFFFAOYSA-N 0.000 description 1
LKCSNVOSTWPREX-PKNBQFBNSA-N 2-[3-[(e)-3-(diphenylcarbamoyloxy)prop-1-enyl]-2-methylphenoxy]acetic acid Chemical compound CC1=C(OCC(O)=O)C=CC=C1\C=C\COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 LKCSNVOSTWPREX-PKNBQFBNSA-N 0.000 description 1
VXZPHOMGJWPZQM-UHFFFAOYSA-N 2-[3-[2-(diphenylcarbamoyloxy)ethyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 VXZPHOMGJWPZQM-UHFFFAOYSA-N 0.000 description 1
AUYNHENMSYOQFH-UHFFFAOYSA-N 2-[3-[3-(diphenylcarbamoyloxy)butyl]phenyl]acetic acid;2-methylpropan-2-amine Chemical compound CC(C)(C)N.C=1C=CC=CC=1N(C=1C=CC=CC=1)C(=O)OC(C)CCC1=CC=CC(CC(O)=O)=C1 AUYNHENMSYOQFH-UHFFFAOYSA-N 0.000 description 1
XRSRWPGBQGLCGC-UHFFFAOYSA-N 2-[3-[3-(diphenylcarbamoyloxy)prop-1-ynyl]-2-methylphenoxy]acetic acid Chemical compound CC1=C(OCC(O)=O)C=CC=C1C#CCOC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 XRSRWPGBQGLCGC-UHFFFAOYSA-N 0.000 description 1
LSGIRIDHTZZPTD-UHFFFAOYSA-N 2-[3-[3-(diphenylcarbamoyloxy)propyl]-2-methylphenyl]acetic acid Chemical compound C1=CC=C(CC(O)=O)C(C)=C1CCCOC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 LSGIRIDHTZZPTD-UHFFFAOYSA-N 0.000 description 1
LJRVKQVRWZOERQ-UHFFFAOYSA-N 2-[3-[3-(diphenylcarbamoyloxy)propyl]-2-methylphenyl]pentanoic acid Chemical compound CCCC(C(O)=O)C1=CC=CC(CCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C LJRVKQVRWZOERQ-UHFFFAOYSA-N 0.000 description 1
WRWDDXULSOOKHR-UHFFFAOYSA-N 2-[3-[4-(diphenylcarbamoyloxy)butyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CCCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 WRWDDXULSOOKHR-UHFFFAOYSA-N 0.000 description 1
ICTGMYXESJYLOV-UHFFFAOYSA-N 2-[3-[5-(diphenylcarbamoyloxy)pentyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CCCCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 ICTGMYXESJYLOV-UHFFFAOYSA-N 0.000 description 1
MJJPJJPRYCDEGT-UHFFFAOYSA-N 2-[3-[6-(diphenylcarbamoyloxy)hexyl]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(CCCCCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 MJJPJJPRYCDEGT-UHFFFAOYSA-N 0.000 description 1
GQUXGBMCLAHHKN-UHFFFAOYSA-N 2-[3-[[cyclohexyl(phenyl)carbamoyl]oxymethyl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(COC(=O)N(C2CCCCC2)C=2C=CC=CC=2)=C1 GQUXGBMCLAHHKN-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
LQIIEHBULBHJKX-UHFFFAOYSA-N 2-methylpropylalumane Chemical compound CC(C)C[AlH2] LQIIEHBULBHJKX-UHFFFAOYSA-N 0.000 description 1
MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 1
DWKWMFSWLCIMKI-UHFFFAOYSA-N 3-(3-bromophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(Br)=C1 DWKWMFSWLCIMKI-UHFFFAOYSA-N 0.000 description 1
XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
FNWZZAKYJCHNKE-UHFFFAOYSA-N 3-[3-(3-hydroxyprop-1-ynyl)phenyl]propanoic acid Chemical compound OCC#CC1=CC=CC(CCC(O)=O)=C1 FNWZZAKYJCHNKE-UHFFFAOYSA-N 0.000 description 1
BYHMLZGICSEKIY-UHFFFAOYSA-N 3-amino-2-methylbenzoic acid Chemical compound CC1=C(N)C=CC=C1C(O)=O BYHMLZGICSEKIY-UHFFFAOYSA-N 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
KVBWBCRPWVKFQT-UHFFFAOYSA-N 3-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(I)=C1 KVBWBCRPWVKFQT-UHFFFAOYSA-N 0.000 description 1
QYHMPRAUVJVVEH-UHFFFAOYSA-N 3-methoxy-2-propan-2-ylbenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1C(C)C QYHMPRAUVJVVEH-UHFFFAOYSA-N 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 1
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
IYDIZBOKVLHCQZ-UHFFFAOYSA-N 9-(9-borabicyclo[3.3.1]nonan-9-yl)-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2B1C2CCCC1CCC2 IYDIZBOKVLHCQZ-UHFFFAOYSA-N 0.000 description 1
200000000007 Arterial disease Diseases 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
DFSDHUAXPJKQLQ-UHFFFAOYSA-N C1=CC=C(OCC(O)=O)C(CC)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound C1=CC=C(OCC(O)=O)C(CC)=C1COC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 DFSDHUAXPJKQLQ-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
101710095468 Cyclase Proteins 0.000 description 1
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
206010014522 Embolism venous Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
206010057671 Female sexual dysfunction Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
206010017577 Gait disturbance Diseases 0.000 description 1
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 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
241000282412 Homo Species 0.000 description 1
206010050394 Hyperkaliuria Diseases 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
206010057672 Male sexual dysfunction Diseases 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
LBFJFLWOFLOWTM-DUXPYHPUSA-N OC\C=C\C1=CC=CC(OCC(O)=O)=C1 Chemical compound OC\C=C\C1=CC=CC(OCC(O)=O)=C1 LBFJFLWOFLOWTM-DUXPYHPUSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241000282579 Pan Species 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
206010065016 Post-traumatic pain Diseases 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
238000006959 Williamson synthesis reaction Methods 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 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
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000005396 acrylic acid ester group Chemical group 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
150000001345 alkine derivatives Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
125000005103 alkyl silyl group Chemical group 0.000 description 1
125000001118 alkylidene group Chemical group 0.000 description 1
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000002965 anti-thrombogenic effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
238000003149 assay kit Methods 0.000 description 1
210000000467 autonomic pathway Anatomy 0.000 description 1
IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
230000008901 benefit Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
125000003460 beta-lactamyl group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000036983 biotransformation Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
210000001772 blood platelet Anatomy 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
230000007883 bronchodilation Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001722 carbon compounds Chemical class 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
208000024980 claudication Diseases 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
229940095074 cyclic amp Drugs 0.000 description 1
230000000593 degrading effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000012954 diazonium Substances 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical group C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 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
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
POCFBDFTJMJWLG-UHFFFAOYSA-N dihydrosinapic acid methyl ester Natural products COC(=O)CCC1=CC(OC)=C(O)C(OC)=C1 POCFBDFTJMJWLG-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
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 1
208000035475 disorder Diseases 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
239000003248 enzyme activator Substances 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
229940125532 enzyme inhibitor Drugs 0.000 description 1
210000002615 epidermis Anatomy 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
RGTTVAWASHIDIH-UHFFFAOYSA-N ethyl 2-bromo-3-methoxybenzoate Chemical compound CCOC(=O)C1=CC=CC(OC)=C1Br RGTTVAWASHIDIH-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
210000004211 gastric acid Anatomy 0.000 description 1
239000003349 gelling agent Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000002363 herbicidal effect Effects 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
230000036543 hypotension Effects 0.000 description 1
HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 1
229960002240 iloprost Drugs 0.000 description 1
230000003832 immune regulation Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000005414 inactive ingredient Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
208000023589 ischemic disease Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
230000036230 kaliuresis Effects 0.000 description 1
210000003127 knee Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000008018 melting Effects 0.000 description 1
IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical group C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 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
230000001617 migratory effect Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
229940051866 mouthwash Drugs 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
DWLVWMUCHSLGSU-UHFFFAOYSA-M n,n-dimethylcarbamate Chemical compound CN(C)C([O-])=O DWLVWMUCHSLGSU-UHFFFAOYSA-M 0.000 description 1
GCLMSHIGZDHMJD-UHFFFAOYSA-N n-cyclohexyl-n-phenylcarbamoyl chloride Chemical compound C=1C=CC=CC=1N(C(=O)Cl)C1CCCCC1 GCLMSHIGZDHMJD-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
150000002790 naphthalenes Chemical class 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
230000010807 negative regulation of binding Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
125000001979 organolithium group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
238000012856 packing Methods 0.000 description 1
238000007427 paired t-test Methods 0.000 description 1
150000002940 palladium Chemical class 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
208000027232 peripheral nervous system disease Diseases 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical class OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N phenyl acetate Chemical group CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
230000008635 plant growth Effects 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000000075 primary alcohol group Chemical group 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000006410 propenylene group Chemical group 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
108050007059 prostanoid receptors Proteins 0.000 description 1
102000017953 prostanoid receptors Human genes 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
235000011182 sodium carbonates Nutrition 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
235000010288 sodium nitrite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007790 solid phase Substances 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
241000894007 species Species 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000005507 spraying Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
238000012353 t test Methods 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
JWYPBBLCPZROOR-UHFFFAOYSA-N tert-butyl 2-(3-bromo-2-methylphenoxy)acetate Chemical compound CC1=C(Br)C=CC=C1OCC(=O)OC(C)(C)C JWYPBBLCPZROOR-UHFFFAOYSA-N 0.000 description 1
ZXGQEZNIBUOWSJ-UHFFFAOYSA-N tert-butyl 2-(3-formyl-2-methylphenoxy)acetate Chemical compound CC1=C(OCC(=O)OC(C)(C)C)C=CC=C1C=O ZXGQEZNIBUOWSJ-UHFFFAOYSA-N 0.000 description 1
RHHVCZIHNBRUCK-UHFFFAOYSA-N tert-butyl 2-[3-(3-hydroxyprop-1-ynyl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)C(C)C1=CC=CC(C#CCO)=C1 RHHVCZIHNBRUCK-UHFFFAOYSA-N 0.000 description 1
KHXBRBGMQUYFGH-UHFFFAOYSA-N tert-butyl 2-[3-[3-(diphenylcarbamoyloxy)prop-1-ynyl]-2-methylphenoxy]acetate Chemical compound CC1=C(OCC(=O)OC(C)(C)C)C=CC=C1C#CCOC(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 KHXBRBGMQUYFGH-UHFFFAOYSA-N 0.000 description 1
NNIANPBPWHBFBO-UHFFFAOYSA-N tert-butyl 2-[3-[3-(diphenylcarbamoyloxy)propyl]phenyl]acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=CC(CCCOC(=O)N(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NNIANPBPWHBFBO-UHFFFAOYSA-N 0.000 description 1
NFEGNISFSSLEGU-UHFFFAOYSA-N tert-butyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC(C)(C)C NFEGNISFSSLEGU-UHFFFAOYSA-N 0.000 description 1
ZYJOSBWOTQEVBZ-UHFFFAOYSA-N tert-butyl 3-(3-bromophenyl)prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=CC1=CC=CC(Br)=C1 ZYJOSBWOTQEVBZ-UHFFFAOYSA-N 0.000 description 1
RVURXEOJGRPZDA-UHFFFAOYSA-N tert-butyl 3-[3-(3-hydroxyprop-1-ynyl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CCC1=CC=CC(C#CCO)=C1 RVURXEOJGRPZDA-UHFFFAOYSA-N 0.000 description 1
PMHAODQGWVSIKE-UHFFFAOYSA-N tert-butyl 4-(3-bromophenyl)butanoate Chemical compound CC(C)(C)OC(=O)CCCC1=CC=CC(Br)=C1 PMHAODQGWVSIKE-UHFFFAOYSA-N 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
XTOWSCXECRARHA-UHFFFAOYSA-N tert-butylazanium;propanoate Chemical compound CCC([O-])=O.CC(C)(C)[NH3+] XTOWSCXECRARHA-UHFFFAOYSA-N 0.000 description 1
230000008719 thickening Effects 0.000 description 1
125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
108090000721 thyroid hormone receptors Proteins 0.000 description 1
238000012549 training Methods 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
UGKSITLWMZJTHC-UHFFFAOYSA-N tribromo-$l^{3}-bromane Chemical compound BrBr(Br)Br UGKSITLWMZJTHC-UHFFFAOYSA-N 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
208000004043 venous thromboembolism Diseases 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- 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
- 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
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Immunology (AREA)
Endocrinology (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Dermatology (AREA)
Vascular Medicine (AREA)
Gynecology & Obstetrics (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyridine Compounds (AREA)

NO19996366A 1998-12-23 1999-12-21 Arylkarboksylsyre- og tetrazolderivater, farmasöytisk preparat samt fremgangsmåte for fremstilling og anvendelse derav NO316171B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US11344698P	1998-12-23	1998-12-23
US15181499P	1999-08-30	1999-08-30

Publications (3)

Publication Number	Publication Date
NO996366D0 NO996366D0 (no)	1999-12-21
NO996366L NO996366L (no)	2000-06-26
NO316171B1 true NO316171B1 (no)	2003-12-22

Family

ID=26811078

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19996366A NO316171B1 (no)	1998-12-23	1999-12-21	Arylkarboksylsyre- og tetrazolderivater, farmasöytisk preparat samt fremgangsmåte for fremstilling og anvendelse derav

Country Status (29)

Country	Link
US (1)	US6335459B1 (es)
EP (1)	EP1013639B1 (es)
JP (1)	JP3415085B2 (es)
KR (1)	KR100378335B1 (es)
CN (1)	CN1167670C (es)
AR (1)	AR029320A1 (es)
AT (1)	ATE251125T1 (es)
AU (1)	AU735640B2 (es)
BR (1)	BR9905974A (es)
CA (1)	CA2292921C (es)
DE (1)	DE69911726T2 (es)
DK (1)	DK1013639T3 (es)
ES (1)	ES2207108T3 (es)
HR (1)	HRP990394A2 (es)
HU (1)	HUP9904659A3 (es)
ID (1)	ID25983A (es)
IL (1)	IL133578A (es)
MA (1)	MA26713A1 (es)
NO (1)	NO316171B1 (es)
NZ (1)	NZ501891A (es)
PE (1)	PE20001368A1 (es)
PL (1)	PL337419A1 (es)
PT (1)	PT1013639E (es)
RU (1)	RU2179969C2 (es)
SG (1)	SG90086A1 (es)
TR (1)	TR199903310A3 (es)
TW (1)	TWI221834B (es)
UY (1)	UY25876A1 (es)
YU (1)	YU69699A (es)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9828442D0 (en)	1998-12-24	1999-02-17	Karobio Ab	Novel thyroid receptor ligands and method II
SE0100158D0 (sv) *	2001-01-19	2001-01-19	Synphora Ab	Novel method and composition for local treatment of Meniere´s disease and tinnitus
JP2004526721A (ja) *	2001-03-02	2004-09-02	エフ．ホフマン−ラ　ロシュ　アーゲー	Ｉｐアンタゴニストとしてのアルコキシカルボニルアミノヘテロアリールカルボン酸誘導体
CA2529351C (en)	2003-05-09	2012-04-17	Toray Industries, Inc.	Use of prostaglandin i for enhancing the effect of a renin-angiotensin system inhibitor on a renal disease
RU2268037C1 (ru) *	2004-04-22	2006-01-20	Германов Евгений Павлович	Лекарственное средство
UA93548C2 (uk)	2006-05-05	2011-02-25	Айерем Елелсі	Сполуки та композиції як модулятори хеджхогівського сигнального шляху
US9669381B2 (en)	2007-06-27	2017-06-06	Hrd Corporation	System and process for hydrocracking
ES2971909T3 (es)	2008-03-18	2024-06-10	Arena Pharm Inc	Composición farmacéutica que comprende: ácido 2-(((1r,4r)-4-(((4-clorofenil)(fenil)carbamoiloxi)metil)ciclohexil)metoxi)acético
KR101587071B1 (ko)	2008-07-23	2016-01-20	도레이 카부시키가이샤	만성 신부전 처치제
WO2011154827A2 (en)	2010-06-11	2011-12-15	Rhodes Technologies	Transition metal-catalyzed processes for the preparation of n-allyl compounds and use thereof
JP2013529595A (ja)	2010-06-11	2013-07-22	ローズテクノロジーズ	第３級アミンのｎ−脱アルキル化方法
IL268997B2 (en)	2017-03-01	2023-09-01	Arena Pharm Inc	Preparations containing pgi2 receptor agonists and processes for their preparation
EP4479374A1 (en)	2022-02-15	2024-12-25	United Therapeutics Corporation	Crystalline prostacyclin (ip) receptor agonist and uses thereof

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1079414A (en)	1965-06-30	1967-08-16	Smith & Nephew	Derivatives of acetic acid and a process for their preparation
GB1185539A (en)	1967-11-03	1970-03-25	Smith & Nephew	Substituted Tetrazoles
DE2432560A1 (de)	1974-07-06	1976-01-22	Boehringer Mannheim Gmbh	Neue phenoxyalkylcarbonsaeurederivate und verfahren zur herstellung derselben
JPS5832859A (ja)	1981-08-20	1983-02-25	Dainippon Pharmaceut Co Ltd	Ｎ，ｎ−ジメチルカルバミン酸ベンジルエステル誘導体
JPH0725725B2 (ja)	1987-07-23	1995-03-22	保土谷化学工業株式会社	ベンズアミド誘導体
US5084466A (en)	1989-01-31	1992-01-28	Hoffmann-La Roche Inc.	Novel carboxamide pyridine compounds which have useful pharmaceutical utility
CA2090283A1 (en)	1992-02-28	1993-08-29	Nobuyuki Hamanaka	Phenoxyacetic acid derivatives
WO1995021863A1 (en)	1994-02-10	1995-08-17	Ono Pharmaceutical Co., Ltd.	Prostaglandin i2 receptor
ATE205479T1 (de)	1994-03-10	2001-09-15	Fujisawa Pharmaceutical Co	Naphtalen-derivate als prostaglandin i2 agonisten
US5753700A (en)	1994-12-28	1998-05-19	Ono Pharmaceutical Co., Ltd.	Naphthyloxyacetic acid derivatives
TW401408B (en)	1995-07-21	2000-08-11	Fujisawa Pharmaceutical Co	Heterocyclic compounds having prostaglandin I2 agonism
WO1997005091A1 (en)	1995-07-26	1997-02-13	Ono Pharmaceutical Co., Ltd.	Naphthyloxyacetic acid derivatives and drugs comprising the same as active ingredients
DE19619445C1 (de) *	1996-05-14	1997-09-25	Bayer Ag	Verfahren zur Herstellung von optisch aktiver N-Phenylcarbamat-milchsäure
AUPP029197A0 (en)	1997-11-10	1997-12-04	Fujisawa Pharmaceutical Co., Ltd.	Benzocycloheptene derivatives
AUPP109097A0 (en)	1997-12-22	1998-01-22	Fujisawa Pharmaceutical Co., Ltd.	Napthalene derivatives

1999
- 1999-12-07 US US09/456,167 patent/US6335459B1/en not_active Expired - Fee Related
- 1999-12-15 DE DE69911726T patent/DE69911726T2/de not_active Expired - Fee Related
- 1999-12-15 PT PT99125027T patent/PT1013639E/pt unknown
- 1999-12-15 EP EP99125027A patent/EP1013639B1/en not_active Expired - Lifetime
- 1999-12-15 DK DK99125027T patent/DK1013639T3/da active
- 1999-12-15 ES ES99125027T patent/ES2207108T3/es not_active Expired - Lifetime
- 1999-12-15 AT AT99125027T patent/ATE251125T1/de not_active IP Right Cessation
- 1999-12-17 IL IL13357899A patent/IL133578A/en not_active IP Right Cessation
- 1999-12-17 NZ NZ501891A patent/NZ501891A/en unknown
- 1999-12-17 AU AU65340/99A patent/AU735640B2/en not_active Ceased
- 1999-12-17 SG SG9906425A patent/SG90086A1/en unknown
- 1999-12-20 HR HR990394A patent/HRP990394A2/hr not_active Application Discontinuation
- 1999-12-20 MA MA25866A patent/MA26713A1/fr unknown
- 1999-12-20 HU HU9904659A patent/HUP9904659A3/hu unknown
- 1999-12-21 PE PE1999001307A patent/PE20001368A1/es not_active Application Discontinuation
- 1999-12-21 NO NO19996366A patent/NO316171B1/no unknown
- 1999-12-21 AR ARP990106638A patent/AR029320A1/es not_active Application Discontinuation
- 1999-12-22 RU RU99127329/04A patent/RU2179969C2/ru not_active IP Right Cessation
- 1999-12-22 JP JP36452099A patent/JP3415085B2/ja not_active Expired - Fee Related
- 1999-12-22 UY UY25876A patent/UY25876A1/es unknown
- 1999-12-22 KR KR10-1999-0060163A patent/KR100378335B1/ko not_active Expired - Fee Related
- 1999-12-22 ID IDP991169D patent/ID25983A/id unknown
- 1999-12-22 CA CA002292921A patent/CA2292921C/en not_active Expired - Fee Related
- 1999-12-23 YU YU69699A patent/YU69699A/sh unknown
- 1999-12-23 TW TW088122774A patent/TWI221834B/zh not_active IP Right Cessation
- 1999-12-23 BR BR9905974-6A patent/BR9905974A/pt not_active IP Right Cessation
- 1999-12-23 CN CNB991277953A patent/CN1167670C/zh not_active Expired - Fee Related
- 1999-12-23 TR TR1999/03310A patent/TR199903310A3/tr unknown
- 1999-12-23 PL PL99337419A patent/PL337419A1/xx not_active Application Discontinuation

Also Published As

Publication number	Publication date
TR199903310A2 (xx)	2000-10-23
TR199903310A3 (tr)	2000-10-23
SG90086A1 (en)	2002-07-23
ATE251125T1 (de)	2003-10-15
NO996366L (no)	2000-06-26
EP1013639B1 (en)	2003-10-01
EP1013639A1 (en)	2000-06-28
HUP9904659A3 (en)	2000-12-28
CA2292921C (en)	2004-08-17
JP3415085B2 (ja)	2003-06-09
DK1013639T3 (da)	2004-02-09
TWI221834B (en)	2004-10-11
HUP9904659A2 (hu)	2000-11-28
YU69699A (sh)	2001-12-26
AR029320A1 (es)	2003-06-25
HRP990394A2 (en)	2000-08-31
DE69911726T2 (de)	2004-07-29
AU735640B2 (en)	2001-07-12
NO996366D0 (no)	1999-12-21
DE69911726D1 (de)	2003-11-06
RU2179969C2 (ru)	2002-02-27
NZ501891A (en)	2001-10-26
CN1266054A (zh)	2000-09-13
KR20000048322A (ko)	2000-07-25
IL133578A (en)	2004-07-25
CA2292921A1 (en)	2000-06-23
PL337419A1 (en)	2000-07-03
MA26713A1 (fr)	2004-12-20
UY25876A1 (es)	2001-07-31
US6335459B1 (en)	2002-01-01
IL133578A0 (en)	2001-04-30
CN1167670C (zh)	2004-09-22
HU9904659D0 (en)	2000-02-28
ES2207108T3 (es)	2004-05-16
PE20001368A1 (es)	2000-12-14
AU6534099A (en)	2000-07-06
ID25983A (id)	2000-11-16
KR100378335B1 (ko)	2003-03-29
JP2000191523A (ja)	2000-07-11
BR9905974A (pt)	2000-09-12
PT1013639E (pt)	2004-02-27

Publication	Publication Date	Title
CN1993346B (zh)	2011-04-27	噻吩化合物
TWI254038B (en)	2006-05-01	N-phenpropylcyclopentyl-substituted glutaramide derivatives as NEP inhibitors for FSAD
RU2315036C2 (ru)	2008-01-20	Антагонист casr
NO316171B1 (no)	2003-12-22	Arylkarboksylsyre- og tetrazolderivater, farmasöytisk preparat samt fremgangsmåte for fremstilling og anvendelse derav
AU2018200368A1 (en)	2018-02-08	Compositions and methods of modulating 15-pgdh activity
KR20010070966A (ko)	2001-07-28	이상지혈증, 아테롬성 동맥 경화증 및 당뇨병의 치료에유용한 고리형 화합물, 약제학적 조성물 및 제조방법
US7902394B2 (en)	2011-03-08	Calcilytic compounds
US20030109570A1 (en)	2003-06-12	Benzothiophene derivatives and medicinal use thereof
KR20080063321A (ko)	2008-07-03	시클로프로필아세트산 유도체 및 그의 용도
WO2002014259A1 (en)	2002-02-21	Calcium receptor antagonists
JPH072848A (ja)	1995-01-06	モルホリンおよびチオモルホリン誘導体
JP4733698B2 (ja)	2011-07-27	α−アリールメトキシアクリレート誘導体を含有する代謝性骨疾患の予防及び治療用医薬組成物
KR20240047401A (ko)	2024-04-12	중수소화 화합물
WO2002000648A1 (en)	2002-01-03	Imidazole derivatives or salts thereof and drugs containing the derivatives or the salts
WO2007143951A1 (en)	2007-12-21	COMPOUNDS WITH THE ACTIVITY OF PPARγ AGONIST AND APPLICATION THEREOF
HUT62557A (en)	1993-05-28	Process for producing n-hydroxi-n\|3-(2-/halogen phenylthio)-phenyl/-prop-2-enyl¨-urea derivatives and pharmaceutical compositions comprising same
MXPA99011894A (es)	2000-10-01	Derivados de acido arilcarboxilico y de tetrazol
RU2144533C1 (ru)	2000-01-20	Производные тетразола, способ их получения и фармацевтические композиции на их основе
JP5075124B2 (ja)	2012-11-14	フルクトース−１，６−ビスホスファターゼ阻害薬としてのイミダゾール誘導体およびそれらを含む医薬組成物
CZ457399A3 (cs)	2000-07-12	Modulátory receptoru prostaglandinu 12 (IP)
US4992459A (en)	1991-02-12	Dopamine-β-hydroxylase inhibitors
US4857663A (en)	1989-08-15	Hypoglycemic N-(2-substituted-3-dialkylamino-2-propenylidene)-N-alkylalkanaminium salts
US4533677A (en)	1985-08-06	Hypoglycemic N-(2-substituted-3-Dialkylamino-2-propenylidene)-N-alkylalkanaminium salts
AU646708B2 (en)	1994-03-03	Imidazol-2-yl derivatives of substituted bicyclic compounds and process for their preparation
JPH09291078A (ja)	1997-11-11	オルトメトキシフェニルピペラジニルアルコキシアリール基を有する新規イミダゾール誘導体及びその製造法