IL133578A - Derivatives of aryl carboxylic acid and aryl tetrazole, and pharmaceutical preparations containing them and processes for their preparation - Google Patents

Derivatives of aryl carboxylic acid and aryl tetrazole, and pharmaceutical preparations containing them and processes for their preparation

Info

Publication number: IL133578A
Authority: IL; Israel
Prior art keywords: compound; acetic acid; independently; compound according; acid
Prior art date: 1998-12-23

Application number

IL13357899A

Other languages

English (en)

Hebrew (he)

Other versions

IL133578A0 (en

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

1999-12-17

Publication date

2004-07-25

1999-12-17 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2001-04-30 Publication of IL133578A0 publication Critical patent/IL133578A0/xx

2004-07-25 Publication of IL133578A publication Critical patent/IL133578A/en

Links

-1 Aryl carboxylic acid Chemical class 0.000 title claims description 96
239000008194 pharmaceutical composition Substances 0.000 title claims description 29
150000001875 compounds Chemical class 0.000 claims abstract description 207
239000000203 mixture Substances 0.000 claims abstract description 121
150000003839 salts Chemical class 0.000 claims abstract description 26
229910052736 halogen Inorganic materials 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 23
239000001257 hydrogen Substances 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
125000002947 alkylene group Chemical group 0.000 claims abstract description 20
239000012453 solvate Substances 0.000 claims abstract description 20
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 abstract description 17
125000004450 alkenylene group Chemical group 0.000 claims abstract description 15
150000002367 halogens Chemical class 0.000 claims abstract description 13
125000003118 aryl group Chemical group 0.000 claims abstract description 12
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 11
150000002431 hydrogen Chemical class 0.000 claims abstract description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
229940075993 receptor modulator Drugs 0.000 claims abstract description 9
125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 8
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 8
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 7
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 118
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 53
201000010099 disease Diseases 0.000 claims description 49
108091006335 Prostaglandin I receptors Proteins 0.000 claims description 39
238000000034 method Methods 0.000 claims description 35
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 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 18
239000003814 drug Substances 0.000 claims description 16
125000001246 bromo group Chemical group Br* 0.000 claims description 15
206010020772 Hypertension Diseases 0.000 claims description 14
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
230000008569 process Effects 0.000 claims description 12
125000001309 chloro group Chemical group Cl* 0.000 claims description 11
206010022562 Intermittent claudication Diseases 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
208000021156 intermittent vascular claudication Diseases 0.000 claims description 9
235000019260 propionic acid Nutrition 0.000 claims description 9
208000021328 arterial occlusion Diseases 0.000 claims description 8
230000002496 gastric effect Effects 0.000 claims description 8
208000028867 ischemia Diseases 0.000 claims description 8
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 8
208000037803 restenosis Diseases 0.000 claims description 8
201000001320 Atherosclerosis Diseases 0.000 claims description 7
208000005171 Dysmenorrhea Diseases 0.000 claims description 7
206010028851 Necrosis Diseases 0.000 claims description 7
206010036600 Premature labour Diseases 0.000 claims description 7
201000001880 Sexual dysfunction Diseases 0.000 claims description 7
208000025865 Ulcer Diseases 0.000 claims description 7
230000001154 acute effect Effects 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
230000017074 necrotic cell death Effects 0.000 claims description 7
210000000440 neutrophil Anatomy 0.000 claims description 7
231100000872 sexual dysfunction Toxicity 0.000 claims description 7
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 7
238000002054 transplantation Methods 0.000 claims description 7
230000036269 ulceration Effects 0.000 claims description 7
230000029663 wound healing Effects 0.000 claims description 7
208000031104 Arterial Occlusive disease Diseases 0.000 claims description 6
208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 claims description 6
206010050394 Hyperkaliuria Diseases 0.000 claims description 6
206010034576 Peripheral ischaemia Diseases 0.000 claims description 6
208000004880 Polyuria Diseases 0.000 claims description 6
208000003782 Raynaud disease Diseases 0.000 claims description 6
208000012322 Raynaud phenomenon Diseases 0.000 claims description 6
206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 6
208000007536 Thrombosis Diseases 0.000 claims description 6
238000002399 angioplasty Methods 0.000 claims description 6
208000029078 coronary artery disease Diseases 0.000 claims description 6
230000035619 diuresis Effects 0.000 claims description 6
230000007365 immunoregulation Effects 0.000 claims description 6
230000036230 kaliuresis Effects 0.000 claims description 6
230000001617 migratory effect Effects 0.000 claims description 6
208000010125 myocardial infarction Diseases 0.000 claims description 6
230000000306 recurrent effect Effects 0.000 claims description 6
201000005060 thrombophlebitis Diseases 0.000 claims description 6
210000003462 vein Anatomy 0.000 claims description 6
208000001647 Renal Insufficiency Diseases 0.000 claims description 5
208000009205 Tinnitus Diseases 0.000 claims description 5
201000006370 kidney failure Diseases 0.000 claims description 5
230000012495 positive regulation of renal sodium excretion Effects 0.000 claims description 5
208000002815 pulmonary hypertension Diseases 0.000 claims description 5
231100000886 tinnitus Toxicity 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 3
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
229960001123 epoprostenol Drugs 0.000 abstract description 3
LMHIPJMTZHDKEW-XQYLJSSYSA-M Epoprostenol sodium Chemical compound [Na+].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 LMHIPJMTZHDKEW-XQYLJSSYSA-M 0.000 abstract 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 92
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 83
239000000243 solution Substances 0.000 description 76
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
238000002360 preparation method Methods 0.000 description 68
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 43
238000006243 chemical reaction Methods 0.000 description 35
239000007787 solid Substances 0.000 description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
238000000746 purification Methods 0.000 description 28
239000000284 extract Substances 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
238000003818 flash chromatography Methods 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
239000002904 solvent Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
239000000018 receptor agonist Substances 0.000 description 18
229940044601 receptor agonist Drugs 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
239000012267 brine Substances 0.000 description 16
239000003960 organic solvent Substances 0.000 description 16
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
125000005843 halogen group Chemical group 0.000 description 15
238000009472 formulation Methods 0.000 description 14
238000003756 stirring Methods 0.000 description 14
238000003556 assay Methods 0.000 description 13
239000002585 base Substances 0.000 description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
239000000843 powder Substances 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
239000010410 layer Substances 0.000 description 12
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
239000012299 nitrogen atmosphere Substances 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
239000003826 tablet Substances 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
239000004480 active ingredient Substances 0.000 description 10
238000004458 analytical method Methods 0.000 description 10
239000012300 argon atmosphere Substances 0.000 description 10
230000017531 blood circulation Effects 0.000 description 10
239000002775 capsule Substances 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
230000000694 effects Effects 0.000 description 10
239000004615 ingredient Substances 0.000 description 10
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 9
150000001733 carboxylic acid esters Chemical class 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
235000011181 potassium carbonates Nutrition 0.000 description 9
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 9
239000000725 suspension Substances 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 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
239000002253 acid Substances 0.000 description 8
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
239000002552 dosage form Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
230000000144 pharmacologic effect Effects 0.000 description 8
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
238000010898 silica gel chromatography Methods 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000007858 starting material Substances 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
241000282472 Canis lupus familiaris Species 0.000 description 7
101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 7
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
239000003937 drug carrier Substances 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
238000001953 recrystallisation Methods 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
238000012360 testing method Methods 0.000 description 7
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
241000124008 Mammalia Species 0.000 description 6
238000005481 NMR spectroscopy Methods 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
239000000556 agonist Substances 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
210000001772 blood platelet Anatomy 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
239000007788 liquid Substances 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
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 5
208000024172 Cardiovascular disease Diseases 0.000 description 5
241000700159 Rattus Species 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
229910000085 borane Inorganic materials 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
239000012467 final product Substances 0.000 description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
125000002346 iodo group Chemical group I* 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
238000010992 reflux 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
239000000126 substance Substances 0.000 description 5
238000001356 surgical procedure Methods 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
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 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
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 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
125000003158 alcohol group Chemical group 0.000 description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
125000003282 alkyl amino group Chemical group 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
239000000969 carrier Substances 0.000 description 4
238000010531 catalytic reduction reaction Methods 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
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CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 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
239000000155 melt Substances 0.000 description 1
IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound 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
229910021645 metal ion Inorganic materials 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
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 1
SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 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
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
210000002464 muscle smooth vascular Anatomy 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
125000001624 naphthyl group Chemical group 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
150000002825 nitriles Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 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
238000006772 olefination reaction Methods 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
150000002895 organic esters Chemical class 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
125000002971 oxazolyl 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
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group 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
235000010603 pastilles Nutrition 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
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
239000000825 pharmaceutical preparation 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
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
239000002953 phosphate buffered saline Substances 0.000 description 1
XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 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
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 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
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 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
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
230000000069 prophylactic effect Effects 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
230000001681 protective effect Effects 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000000700 radioactive tracer Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000001105 regulatory 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
238000007363 ring formation reaction 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
230000007017 scission Effects 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
210000002460 smooth muscle Anatomy 0.000 description 1
235000011182 sodium carbonates Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 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
230000003595 spectral effect Effects 0.000 description 1
239000008117 stearic acid Chemical group 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000000153 supplemental effect Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
230000002459 sustained effect Effects 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
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
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 1
NGJUMJUGZQRXNQ-FNORWQNLSA-N tert-butyl 2-[3-[(e)-3-hydroxyprop-1-enyl]phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=CC(\C=C\CO)=C1 NGJUMJUGZQRXNQ-FNORWQNLSA-N 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000008719 thickening Effects 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
230000002885 thrombogenetic effect Effects 0.000 description 1
108090000721 thyroid hormone receptors Proteins 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
238000005809 transesterification reaction Methods 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
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
235000019798 tripotassium phosphate Nutrition 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 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
229920002554 vinyl polymer Polymers 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000009736 wetting Methods 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)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Immunology (AREA)
Diabetes (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Vascular Medicine (AREA)
Gynecology & Obstetrics (AREA)
Dermatology (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)

IL13357899A 1998-12-23 1999-12-17 Derivatives of aryl carboxylic acid and aryl tetrazole, and pharmaceutical preparations containing them and processes for their preparation IL133578A (en)

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 (2)

Publication Number	Publication Date
IL133578A0 IL133578A0 (en)	2001-04-30
IL133578A true IL133578A (en)	2004-07-25

Family

ID=26811078

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL13357899A IL133578A (en)	1998-12-23	1999-12-17	Derivatives of aryl carboxylic acid and aryl tetrazole, and pharmaceutical preparations containing them and processes for their preparation

Country Status (29)

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

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
CA2438813C (fr) *	2001-03-02	2008-07-29	F. Hoffmann-La Roche Ag	Derives d'acide alcoxycarbonylaminoheteroaryle carboxylique en tant qu'antagonistes d'ip
ES2636943T3 (es)	2003-05-09	2017-10-10	Toray Industries, Inc.	Beraprost y un inhibidor del sistema renina-angiotensina para usar en el tratamiento de enfermedades renales
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
KR20230085944A (ko)	2008-03-18	2023-06-14	아레나 파마슈티칼스, 인크.	프로스타시클린 （ｐｇｉ２） 수용체와 관련된 장애의 치료에 유용한 상기 수용체의 조절제
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1999
- 1999-12-07 US US09/456,167 patent/US6335459B1/en not_active Expired - Fee Related
- 1999-12-15 ES ES99125027T patent/ES2207108T3/es not_active Expired - Lifetime
- 1999-12-15 PT PT99125027T patent/PT1013639E/pt unknown
- 1999-12-15 DE DE69911726T patent/DE69911726T2/de not_active Expired - Fee Related
- 1999-12-15 AT AT99125027T patent/ATE251125T1/de not_active IP Right Cessation
- 1999-12-15 DK DK99125027T patent/DK1013639T3/da active
- 1999-12-15 EP EP99125027A patent/EP1013639B1/fr not_active Expired - Lifetime
- 1999-12-17 NZ NZ501891A patent/NZ501891A/en unknown
- 1999-12-17 SG SG9906425A patent/SG90086A1/en unknown
- 1999-12-17 AU AU65340/99A patent/AU735640B2/en not_active Ceased
- 1999-12-17 IL IL13357899A patent/IL133578A/en not_active IP Right Cessation
- 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 KR KR10-1999-0060163A patent/KR100378335B1/ko not_active Expired - Fee Related
- 1999-12-22 ID IDP991169D patent/ID25983A/id unknown
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- 1999-12-22 RU RU99127329/04A patent/RU2179969C2/ru not_active IP Right Cessation
- 1999-12-22 CA CA002292921A patent/CA2292921C/fr not_active Expired - Fee Related
- 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 YU YU69699A patent/YU69699A/sh unknown
- 1999-12-23 PL PL99337419A patent/PL337419A1/xx not_active Application Discontinuation
- 1999-12-23 BR BR9905974-6A patent/BR9905974A/pt not_active IP Right Cessation
- 1999-12-23 TW TW088122774A patent/TWI221834B/zh not_active IP Right Cessation

Also Published As

Publication number	Publication date
ES2207108T3 (es)	2004-05-16
YU69699A (sh)	2001-12-26
NZ501891A (en)	2001-10-26
TR199903310A2 (xx)	2000-10-23
SG90086A1 (en)	2002-07-23
BR9905974A (pt)	2000-09-12
PE20001368A1 (es)	2000-12-14
AU6534099A (en)	2000-07-06
EP1013639B1 (fr)	2003-10-01
RU2179969C2 (ru)	2002-02-27
IL133578A0 (en)	2001-04-30
CA2292921A1 (fr)	2000-06-23
KR20000048322A (ko)	2000-07-25
NO996366D0 (no)	1999-12-21
JP2000191523A (ja)	2000-07-11
HUP9904659A3 (en)	2000-12-28
DE69911726T2 (de)	2004-07-29
KR100378335B1 (ko)	2003-03-29
HU9904659D0 (en)	2000-02-28
TWI221834B (en)	2004-10-11
ATE251125T1 (de)	2003-10-15
PL337419A1 (en)	2000-07-03
DK1013639T3 (da)	2004-02-09
TR199903310A3 (tr)	2000-10-23
DE69911726D1 (de)	2003-11-06
AR029320A1 (es)	2003-06-25
HUP9904659A2 (hu)	2000-11-28
CA2292921C (fr)	2004-08-17
JP3415085B2 (ja)	2003-06-09
PT1013639E (pt)	2004-02-27
UY25876A1 (es)	2001-07-31
NO996366L (no)	2000-06-26
AU735640B2 (en)	2001-07-12
HRP990394A2 (en)	2000-08-31
US6335459B1 (en)	2002-01-01
EP1013639A1 (fr)	2000-06-28
CN1266054A (zh)	2000-09-13
MA26713A1 (fr)	2004-12-20
NO316171B1 (no)	2003-12-22
ID25983A (id)	2000-11-16
CN1167670C (zh)	2004-09-22

Legal Events

Date	Code	Title	Description
2004-12-15	FF	Patent granted
2006-01-15	MM9K	Patent not in force due to non-payment of renewal fees

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