NO327635B1 - Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike - Google Patents

Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike Download PDF

Info

Publication number: NO327635B1
Authority: NO; Norway
Prior art keywords: formula; compound according; compound; phenyl; alkyl
Prior art date: 2001-07-19

Application number

NO20040234A

Other languages

English (en)

Norwegian (no)

Other versions

NO20040234L (no

Inventor

Prabha N Ibrahim

Jeff A Zablocki

Elfatih O Elzein

Kevin Shenk

Venkata Palle

Kenneth Rehder

Original Assignee

Cv Therapeutics Inc

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

2001-07-19

Filing date

2004-01-19

Publication date

2009-09-07

2004-01-19 Application filed by Cv Therapeutics Inc filed Critical Cv Therapeutics Inc

2004-03-18 Publication of NO20040234L publication Critical patent/NO20040234L/no

2009-09-07 Publication of NO327635B1 publication Critical patent/NO327635B1/no

Links

150000004885 piperazines Chemical class 0.000 title description 5
239000008194 pharmaceutical composition Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 248
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
201000010099 disease Diseases 0.000 claims abstract description 15
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 12
241000124008 Mammalia Species 0.000 claims abstract description 9
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
206010022562 Intermittent claudication Diseases 0.000 claims abstract description 6
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
208000021156 intermittent vascular claudication Diseases 0.000 claims abstract description 6
208000010125 myocardial infarction Diseases 0.000 claims abstract description 6
206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 5
206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 5
208000007718 Stable Angina Diseases 0.000 claims abstract description 5
206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
-1 C3-C7-cycloalkyl Chemical group 0.000 claims description 111
238000002360 preparation method Methods 0.000 claims description 55
125000001424 substituent group Chemical group 0.000 claims description 54
229910052736 halogen Inorganic materials 0.000 claims description 32
150000002367 halogens Chemical class 0.000 claims description 32
230000003647 oxidation Effects 0.000 claims description 32
238000007254 oxidation reaction Methods 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 31
229910052739 hydrogen Inorganic materials 0.000 claims description 31
229910052760 oxygen Inorganic materials 0.000 claims description 31
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
239000001301 oxygen Substances 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 26
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 19
235000014113 dietary fatty acids Nutrition 0.000 claims description 17
239000000194 fatty acid Substances 0.000 claims description 17
229930195729 fatty acid Natural products 0.000 claims description 17
150000004665 fatty acids Chemical class 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000002947 alkylene group Chemical group 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
239000003112 inhibitor Substances 0.000 claims description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
239000000825 pharmaceutical preparation Substances 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
210000001519 tissue Anatomy 0.000 claims description 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
229910052717 sulfur Chemical group 0.000 claims description 6
239000011593 sulfur Chemical group 0.000 claims description 6
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
125000002971 oxazolyl group Chemical group 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 4
208000014674 injury Diseases 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
239000004305 biphenyl Substances 0.000 claims description 3
235000010290 biphenyl Nutrition 0.000 claims description 3
230000006378 damage Effects 0.000 claims description 3
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
230000035939 shock Effects 0.000 claims description 3
210000002027 skeletal muscle Anatomy 0.000 claims description 3
230000008733 trauma Effects 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 2
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
125000004193 piperazinyl group Chemical group 0.000 claims 2
WYDWTECDFUFLJT-UHFFFAOYSA-N 1-[4-[[5-(4-chlorophenyl)-1,2-oxazol-3-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=NO1)C=C1C1=CC=C(Cl)C=C1 WYDWTECDFUFLJT-UHFFFAOYSA-N 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 claims 1
125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 abstract description 21
230000001746 atrial effect Effects 0.000 abstract description 7
206010002388 Angina unstable Diseases 0.000 abstract description 2
208000007814 Unstable Angina Diseases 0.000 abstract description 2
201000004332 intermediate coronary syndrome Diseases 0.000 abstract description 2
230000036470 plasma concentration Effects 0.000 abstract 1
125000000217 alkyl group Chemical group 0.000 description 58
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
239000000203 mixture Substances 0.000 description 55
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 51
239000000243 solution Substances 0.000 description 51
125000001072 heteroaryl group Chemical group 0.000 description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
125000003118 aryl group Chemical group 0.000 description 43
239000002904 solvent Substances 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
238000000034 method Methods 0.000 description 34
230000002829 reductive effect Effects 0.000 description 32
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 28
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
125000003545 alkoxy group Chemical group 0.000 description 27
239000008103 glucose Substances 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
229910001868 water Inorganic materials 0.000 description 26
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
125000004181 carboxyalkyl group Chemical group 0.000 description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
239000000047 product Substances 0.000 description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
125000003342 alkenyl group Chemical group 0.000 description 20
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 20
239000012442 inert solvent Substances 0.000 description 19
125000000753 cycloalkyl group Chemical group 0.000 description 18
239000003826 tablet Substances 0.000 description 18
239000004480 active ingredient Substances 0.000 description 17
125000000304 alkynyl group Chemical group 0.000 description 17
125000000392 cycloalkenyl group Chemical group 0.000 description 16
230000010412 perfusion Effects 0.000 description 15
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 14
150000003839 salts Chemical class 0.000 description 14
239000000706 filtrate Substances 0.000 description 13
210000002216 heart Anatomy 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000000843 powder Substances 0.000 description 13
150000001412 amines Chemical class 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
125000004414 alkyl thio group Chemical group 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
229930194542 Keto Natural products 0.000 description 10
125000002252 acyl group Chemical group 0.000 description 10
125000004442 acylamino group Chemical group 0.000 description 10
125000004423 acyloxy group Chemical group 0.000 description 10
125000005110 aryl thio group Chemical group 0.000 description 10
125000004104 aryloxy group Chemical group 0.000 description 10
239000002585 base Substances 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
125000005553 heteroaryloxy group Chemical group 0.000 description 10
125000000468 ketone group Chemical group 0.000 description 10
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 10
150000003573 thiols Chemical class 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 9
125000000033 alkoxyamino group Chemical group 0.000 description 9
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 9
125000006598 aminocarbonylamino group Chemical group 0.000 description 9
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 9
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 9
230000000747 cardiac effect Effects 0.000 description 9
230000034659 glycolysis Effects 0.000 description 9
125000005368 heteroarylthio group Chemical group 0.000 description 9
125000004470 heterocyclooxy group Chemical group 0.000 description 9
125000004468 heterocyclylthio group Chemical group 0.000 description 9
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 9
239000004615 ingredient Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
238000012360 testing method Methods 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 8
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
125000000547 substituted alkyl group Chemical group 0.000 description 8
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 8
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
238000009472 formulation Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
YBJJKPOQWUEERM-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCNCC1 YBJJKPOQWUEERM-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
125000004429 atom Chemical group 0.000 description 6
235000013405 beer Nutrition 0.000 description 6
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
239000007788 liquid Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000005259 measurement Methods 0.000 description 6
150000007530 organic bases Chemical class 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000007858 starting material Substances 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000007789 gas Substances 0.000 description 5
150000002430 hydrocarbons Chemical group 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
230000036316 preload Effects 0.000 description 5
125000003107 substituted aryl group Chemical group 0.000 description 5
239000000725 suspension Substances 0.000 description 5
TWENMNQDGGICPL-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propyl]piperazine-1-carboxylate Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 TWENMNQDGGICPL-UHFFFAOYSA-N 0.000 description 5
LAKVUPMDDFICNR-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-ol Chemical compound OC1=CC=C2SC(C)=NC2=C1 LAKVUPMDDFICNR-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
XKLMZUWKNUAPSZ-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC=2C(=CC=CC=2C)C)CC1 XKLMZUWKNUAPSZ-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000001914 filtration Methods 0.000 description 4
230000002107 myocardial effect Effects 0.000 description 4
230000036284 oxygen consumption Effects 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000006187 pill Substances 0.000 description 4
238000012746 preparative thin layer chromatography Methods 0.000 description 4
229930195734 saturated hydrocarbon Natural products 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000003756 stirring Methods 0.000 description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
XCARGDPHZYJCMU-UHFFFAOYSA-N 2-chloro-n'-hydroxyethanimidamide Chemical compound ClCC(N)=NO XCARGDPHZYJCMU-UHFFFAOYSA-N 0.000 description 3
YSPRCDGVFRVBED-UHFFFAOYSA-N 2-methyl-5-(oxiran-2-ylmethoxy)-1,3-benzothiazole Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC1CO1 YSPRCDGVFRVBED-UHFFFAOYSA-N 0.000 description 3
ZLQQUIHBQATFOP-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-5-(chloromethyl)-1,2,4-oxadiazole Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NOC(CCl)=N1 ZLQQUIHBQATFOP-UHFFFAOYSA-N 0.000 description 3
230000002407 ATP formation Effects 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000003710 aryl alkyl group Chemical group 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000003638 chemical reducing agent Substances 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
238000000576 coating method Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
150000002118 epoxides Chemical class 0.000 description 3
238000011067 equilibration Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000000415 inactivating effect Effects 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
238000006213 oxygenation reaction Methods 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000000746 purification Methods 0.000 description 3
229960000213 ranolazine Drugs 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
125000005017 substituted alkenyl group Chemical group 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
BRLQWZUYTZBJKN-GSVOUGTGSA-N (+)-Epichlorohydrin Chemical compound ClC[C@@H]1CO1 BRLQWZUYTZBJKN-GSVOUGTGSA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
OHIMGDQOEPFSSL-UHFFFAOYSA-N 1-(2-chloroethyl)-4-(4-fluorophenyl)pyrazole Chemical compound C1=CC(F)=CC=C1C1=CN(CCCl)N=C1 OHIMGDQOEPFSSL-UHFFFAOYSA-N 0.000 description 2
AWACTBIAMFXSIT-UHFFFAOYSA-N 1-(2-chloroethyl)-4-iodopyrazole Chemical compound ClCCN1C=C(I)C=N1 AWACTBIAMFXSIT-UHFFFAOYSA-N 0.000 description 2
SGPXVDUKDPINQL-UHFFFAOYSA-N 1-(2-fluorophenoxy)-3-piperazin-1-ylpropan-2-ol Chemical compound C1CNCCN1CC(O)COC1=CC=CC=C1F SGPXVDUKDPINQL-UHFFFAOYSA-N 0.000 description 2
QBGTXMSLUMBNOV-UHFFFAOYSA-N 1-[(2-cyclohexyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C1CNCCN1CC(O)COC(C=C1N=2)=CC=C1SC=2C1CCCCC1 QBGTXMSLUMBNOV-UHFFFAOYSA-N 0.000 description 2
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 2
VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
ZGBJAUZQXAADQJ-UHFFFAOYSA-N 2-[(2-fluorophenoxy)methyl]oxirane Chemical compound FC1=CC=CC=C1OCC1OC1 ZGBJAUZQXAADQJ-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 2
YCOKTYBAJSXBTK-UHFFFAOYSA-N 3-(chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2ON=C(CCl)N=2)=C1 YCOKTYBAJSXBTK-UHFFFAOYSA-N 0.000 description 2
FOPHIEABULMTDJ-UHFFFAOYSA-N 3-(chloromethyl)-5-[4-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC(CCl)=NO1 FOPHIEABULMTDJ-UHFFFAOYSA-N 0.000 description 2
JZTPKAROPNTQQV-UHFFFAOYSA-N 3-fluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1 JZTPKAROPNTQQV-UHFFFAOYSA-N 0.000 description 2
SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 2
OXZYBOLWRXENKT-UHFFFAOYSA-N 4-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=C(C(Cl)=O)C=C1 OXZYBOLWRXENKT-UHFFFAOYSA-N 0.000 description 2
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 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
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-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
229930195725 Mannitol Natural products 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-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
241000700159 Rattus Species 0.000 description 2
206010063837 Reperfusion injury Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-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
FCVSGLPWXVBEHT-UHFFFAOYSA-N [2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methanol Chemical compound OCC1=COC(C=2C=CC(=CC=2)C(F)(F)F)=N1 FCVSGLPWXVBEHT-UHFFFAOYSA-N 0.000 description 2
HTDMXATWYNKLLE-UHFFFAOYSA-N [5-[4-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methanol Chemical compound O1N=C(CO)C=C1C1=CC=C(C(F)(F)F)C=C1 HTDMXATWYNKLLE-UHFFFAOYSA-N 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000003899 bactericide agent Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
238000013270 controlled release Methods 0.000 description 2
229920001577 copolymer Polymers 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000002612 dispersion medium Substances 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
PLWDXYITTPOTKK-UHFFFAOYSA-N ethyl 2-chloro-2-(hydroxyamino)acetate Chemical compound CCOC(=O)C(Cl)NO PLWDXYITTPOTKK-UHFFFAOYSA-N 0.000 description 2
MKMLEMDGZCVWJB-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC=C(C(F)(F)F)C=C1 MKMLEMDGZCVWJB-UHFFFAOYSA-N 0.000 description 2
WWWSJJPBJGEKKY-UHFFFAOYSA-N ethyl 5-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,2-oxazole-3-carboxylate Chemical compound C1C(C(=O)OCC)=NOC1C1=CC=C(C(F)(F)F)C=C1 WWWSJJPBJGEKKY-UHFFFAOYSA-N 0.000 description 2
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
125000005549 heteroarylene group Chemical group 0.000 description 2
150000002391 heterocyclic compounds Chemical class 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
208000028867 ischemia Diseases 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
150000002545 isoxazoles Chemical class 0.000 description 2
125000000842 isoxazolyl group Chemical group 0.000 description 2
239000008101 lactose Substances 0.000 description 2
210000005246 left atrium Anatomy 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
230000005226 mechanical processes and functions Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
RXTILVJDUGFFKT-UHFFFAOYSA-N methyl 2-[4-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(C=2C=CC(=CC=2)C(F)(F)F)=N1 RXTILVJDUGFFKT-UHFFFAOYSA-N 0.000 description 2
RQDYZAGLOUDTFE-UHFFFAOYSA-N methyl 2-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1COC(C=2C=CC(=CC=2)C(F)(F)F)=N1 RQDYZAGLOUDTFE-UHFFFAOYSA-N 0.000 description 2
NNAFQSOVRVRNKE-UHFFFAOYSA-N methyl 3-hydroxy-2-[[4-(trifluoromethyl)benzoyl]amino]propanoate Chemical compound COC(=O)C(CO)NC(=O)C1=CC=C(C(F)(F)F)C=C1 NNAFQSOVRVRNKE-UHFFFAOYSA-N 0.000 description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
NXPSDGKZHWRAII-UHFFFAOYSA-N n'-(3-fluorophenyl)-n-hydroxymethanimidamide Chemical compound ONC=NC1=CC=CC(F)=C1 NXPSDGKZHWRAII-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
150000002916 oxazoles Chemical class 0.000 description 2
239000002245 particle Substances 0.000 description 2
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
239000008177 pharmaceutical agent Substances 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001103 potassium chloride Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
239000003586 protic polar solvent Substances 0.000 description 2
210000001147 pulmonary artery Anatomy 0.000 description 2
230000009467 reduction 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
239000000523 sample Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000000926 separation method Methods 0.000 description 2
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
125000004426 substituted alkynyl group Chemical group 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
239000000829 suppository Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
230000035488 systolic blood pressure Effects 0.000 description 2
JRKIQTUHRLQDGZ-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]propyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=C(OC(=N2)C=3C=CC=CC=3)C2=C1 JRKIQTUHRLQDGZ-UHFFFAOYSA-N 0.000 description 2
RWTHEIZJLZKKAQ-UHFFFAOYSA-N tert-butyl 4-[3-(2-fluorophenoxy)-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=CC=C1F RWTHEIZJLZKKAQ-UHFFFAOYSA-N 0.000 description 2
YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
230000002861 ventricular Effects 0.000 description 2
229920002554 vinyl polymer Polymers 0.000 description 2
238000005303 weighing Methods 0.000 description 2
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
NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-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
150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
HVPPJURUTODQOY-UHFFFAOYSA-N 1-(2-methoxyphenoxy)-3-piperazin-1-ylpropan-2-ol Chemical compound COC1=CC=CC=C1OCC(O)CN1CCNCC1 HVPPJURUTODQOY-UHFFFAOYSA-N 0.000 description 1
RWSGMHHCXDIKKP-UHFFFAOYSA-N 1-(4-methoxyphenoxy)-3-[4-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound C1=CC(OC)=CC=C1OCC(O)CN1CCN(CC=2N=C(ON=2)C=2C=C(C=CC=2)C(F)(F)F)CC1 RWSGMHHCXDIKKP-UHFFFAOYSA-N 0.000 description 1
LOHBUGASUBABIT-UHFFFAOYSA-N 1-(4-methoxyphenoxy)-3-piperazin-1-ylpropan-2-ol Chemical compound C1=CC(OC)=CC=C1OCC(O)CN1CCNCC1 LOHBUGASUBABIT-UHFFFAOYSA-N 0.000 description 1
NWQJDOGMXCKWPP-UHFFFAOYSA-N 1-(4-methylimidazol-4-yl)oxy-3-piperazin-1-ylpropan-2-ol Chemical compound C1CNCCN1CC(O)COC1(C)C=NC=N1 NWQJDOGMXCKWPP-UHFFFAOYSA-N 0.000 description 1
WYNLFVODYBXRBZ-UHFFFAOYSA-N 1-[(2-ethyl-1,3-thiazol-4-yl)oxy]-3-[4-[[5-(2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound S1C(CC)=NC(OCC(O)CN2CCN(CC=3N=C(ON=3)C=3C(=CC=CC=3)OC)CC2)=C1 WYNLFVODYBXRBZ-UHFFFAOYSA-N 0.000 description 1
OIIZRNOFPGQLJW-UHFFFAOYSA-N 1-[(2-ethyl-1,3-thiazol-4-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound S1C(CC)=NC(OCC(O)CN2CCNCC2)=C1 OIIZRNOFPGQLJW-UHFFFAOYSA-N 0.000 description 1
DYFCVQIAKHSRPP-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[4-[(2-methyl-1,3-thiazol-4-yl)methyl]piperazin-1-yl]propan-2-ol Chemical compound S1C(C)=NC(CN2CCN(CC(O)COC=3C=C4N=C(C)SC4=CC=3)CC2)=C1 DYFCVQIAKHSRPP-UHFFFAOYSA-N 0.000 description 1
QTAYYFJMVXNUMZ-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[4-[(5-methyl-1,2-oxazol-3-yl)methyl]piperazin-1-yl]propan-2-ol Chemical compound O1C(C)=CC(CN2CCN(CC(O)COC=3C=C4N=C(C)SC4=CC=3)CC2)=N1 QTAYYFJMVXNUMZ-UHFFFAOYSA-N 0.000 description 1
PYUAONCDAVXNNW-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-[4-[[5-[4-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methyl]piperazin-1-yl]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(=NO1)C=C1C1=CC=C(C(F)(F)F)C=C1 PYUAONCDAVXNNW-UHFFFAOYSA-N 0.000 description 1
UGLWNPUTMXHTCB-UHFFFAOYSA-N 1-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol;hydrochloride Chemical compound Cl.C=1C=C2SC(C)=NC2=CC=1OCC(O)CN1CCNCC1 UGLWNPUTMXHTCB-UHFFFAOYSA-N 0.000 description 1
PSOCQVNBSDJELW-UHFFFAOYSA-N 1-[(2-methyl-3h-benzimidazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C1=C2NC(C)=NC2=CC=C1OCC(O)CN1CCNCC1 PSOCQVNBSDJELW-UHFFFAOYSA-N 0.000 description 1
XNKHULXLPJZLGU-UHFFFAOYSA-N 1-[(2-phenyl-1,3-benzothiazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C1CNCCN1CC(O)COC(C=C1N=2)=CC=C1SC=2C1=CC=CC=C1 XNKHULXLPJZLGU-UHFFFAOYSA-N 0.000 description 1
DOEIINIZIVKBTL-UHFFFAOYSA-N 1-[(2-phenyl-3h-benzimidazol-5-yl)oxy]-3-piperazin-1-ylpropan-2-ol Chemical compound C1CNCCN1CC(O)COC(C=C1N2)=CC=C1N=C2C1=CC=CC=C1 DOEIINIZIVKBTL-UHFFFAOYSA-N 0.000 description 1
OXPKAZOHHTXJLP-UHFFFAOYSA-N 1-[4-[(2-methyl-1,3-thiazol-4-yl)methyl]piperazin-1-yl]-3-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]propan-2-ol Chemical compound S1C(C)=NC(CN2CCN(CC(O)COC=3C=C4N=C(OC4=CC=3)C=3C=CC=CC=3)CC2)=C1 OXPKAZOHHTXJLP-UHFFFAOYSA-N 0.000 description 1
KSHAWAUMLXMJMU-UHFFFAOYSA-N 1-[4-[(5-methyl-1,2-oxazol-3-yl)methyl]piperazin-1-yl]-3-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]propan-2-ol Chemical compound O1C(C)=CC(CN2CCN(CC(O)COC=3C=C4N=C(OC4=CC=3)C=3C=CC=CC=3)CC2)=N1 KSHAWAUMLXMJMU-UHFFFAOYSA-N 0.000 description 1
CECQODHRJPHCPJ-UHFFFAOYSA-N 1-[4-[[2-(3,5-dimethyl-1,2-oxazol-4-yl)-3h-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-3-[(2-phenyl-1,3-benzoxazol-5-yl)oxy]propan-2-ol Chemical compound CC1=NOC(C)=C1N1C(CN2CCN(CC(O)COC=3C=C4N=C(OC4=CC=3)C=3C=CC=CC=3)CC2)N=CO1 CECQODHRJPHCPJ-UHFFFAOYSA-N 0.000 description 1
ZSBJSWKDJGBMNW-UHFFFAOYSA-N 1-[4-[[3-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-oxadiazol-5-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(ON=1)=NC=1C=1C(C)=NOC=1C ZSBJSWKDJGBMNW-UHFFFAOYSA-N 0.000 description 1
SMGHSWQQLDOYPU-UHFFFAOYSA-N 1-[4-[[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(ON=1)=NC=1C1=CC=CC(F)=C1 SMGHSWQQLDOYPU-UHFFFAOYSA-N 0.000 description 1
WXQZGMFZSUJXEE-UHFFFAOYSA-N 1-[4-[[3-(4-tert-butylphenyl)-1,2,4-oxadiazol-5-yl]methyl]piperazin-1-yl]-3-[(2-methyl-1,3-benzothiazol-5-yl)oxy]propan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCC(O)CN(CC1)CCN1CC(ON=1)=NC=1C1=CC=C(C(C)(C)C)C=C1 WXQZGMFZSUJXEE-UHFFFAOYSA-N 0.000 description 1
LYQYNUBKIHARAN-UHFFFAOYSA-N 1-[4-[[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-3-(1-fluoronaphthalen-2-yl)oxypropan-2-ol Chemical compound C=1C=C2C=CC=CC2=C(F)C=1OCC(O)CN(CC1)CCN1CC(N=1)=NOC=1C1=CC=C(Cl)C=C1 LYQYNUBKIHARAN-UHFFFAOYSA-N 0.000 description 1
IRNHWGYHJGFCGD-UHFFFAOYSA-N 1-[4-[[5-(4-tert-butylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-3-(2-fluorophenoxy)-1-piperazin-1-ylpropan-2-ol Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC(CN2CCN(CC2)C(C(O)COC=2C(=CC=CC=2)F)N2CCNCC2)=NO1 IRNHWGYHJGFCGD-UHFFFAOYSA-N 0.000 description 1
IHRSWFQDIGMIOU-UHFFFAOYSA-N 1-[4-[[5-(4-tert-butylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-3-(2-fluorophenoxy)propan-2-ol Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC(CN2CCN(CC(O)COC=3C(=CC=CC=3)F)CC2)=NO1 IHRSWFQDIGMIOU-UHFFFAOYSA-N 0.000 description 1
CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 1
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
CKLYNKVPJLVQDN-UHFFFAOYSA-N 2-[(1-fluoronaphthalen-2-yl)oxymethyl]oxirane Chemical compound C1=CC2=CC=CC=C2C(F)=C1OCC1CO1 CKLYNKVPJLVQDN-UHFFFAOYSA-N 0.000 description 1
RJNVSQLNEALZLC-UHFFFAOYSA-N 2-[(2-methoxyphenoxy)methyl]oxirane Chemical compound COC1=CC=CC=C1OCC1OC1 RJNVSQLNEALZLC-UHFFFAOYSA-N 0.000 description 1
AVWGFHZLPMLKBL-UHFFFAOYSA-N 2-[(4-methoxyphenoxy)methyl]oxirane Chemical compound C1=CC(OC)=CC=C1OCC1OC1 AVWGFHZLPMLKBL-UHFFFAOYSA-N 0.000 description 1
MTRCETJEPUOHTJ-UHFFFAOYSA-N 2-[(8-fluoronaphthalen-1-yl)oxymethyl]oxirane Chemical compound C=12C(F)=CC=CC2=CC=CC=1OCC1CO1 MTRCETJEPUOHTJ-UHFFFAOYSA-N 0.000 description 1
LUKMAFPGZSTOEK-UHFFFAOYSA-N 2-[2-(2-chlorophenoxy)ethyl]oxirane Chemical compound ClC1=CC=CC=C1OCCC1OC1 LUKMAFPGZSTOEK-UHFFFAOYSA-N 0.000 description 1
XWHSQDHACDTMLY-UHFFFAOYSA-N 2-[2-(2-methoxyphenoxy)ethyl]oxirane Chemical compound COC1=CC=CC=C1OCCC1OC1 XWHSQDHACDTMLY-UHFFFAOYSA-N 0.000 description 1
LGZCUZBOHJWPNT-UHFFFAOYSA-N 2-[4-[[5-(4-tert-butylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-4-(2-chlorophenoxy)butan-2-ol Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC(CN2CCN(CC2)C(C)(O)CCOC=2C(=CC=CC=2)Cl)=NO1 LGZCUZBOHJWPNT-UHFFFAOYSA-N 0.000 description 1
DCZRUYTYLJSKCE-UHFFFAOYSA-N 2-[4-[[5-(4-tert-butylphenyl)-1,2,4-oxadiazol-3-yl]methyl]piperazin-1-yl]-4-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-1-piperazin-1-ylbutan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCC(O)(N1CCN(CC=2N=C(ON=2)C=2C=CC(=CC=2)C(C)(C)C)CC1)CN1CCNCC1 DCZRUYTYLJSKCE-UHFFFAOYSA-N 0.000 description 1
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
YCZLJRIAGHPLRO-UHFFFAOYSA-N 2-ethyl-4-(oxiran-2-ylmethoxy)-1,3-thiazole Chemical compound S1C(CC)=NC(OCC2OC2)=C1 YCZLJRIAGHPLRO-UHFFFAOYSA-N 0.000 description 1
QBPIMPLQFDKJDD-UHFFFAOYSA-N 2-methyl-5-(3-piperazin-1-ylpropoxy)-1,3-benzothiazole Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCCN1CCNCC1 QBPIMPLQFDKJDD-UHFFFAOYSA-N 0.000 description 1
DILGZUDEEZNFOL-UHFFFAOYSA-N 2-methyl-5-[2-(oxiran-2-yl)ethoxy]-1,3-benzothiazole Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCC1CO1 DILGZUDEEZNFOL-UHFFFAOYSA-N 0.000 description 1
YBIGZIJBVCJGIV-UHFFFAOYSA-N 2-methyl-6-(oxiran-2-ylmethoxy)-1h-benzimidazole Chemical compound C1=C2NC(C)=NC2=CC=C1OCC1CO1 YBIGZIJBVCJGIV-UHFFFAOYSA-N 0.000 description 1
VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
WPSCQFMIKNCXTH-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazol-5-ol Chemical compound N=1C2=CC(O)=CC=C2OC=1C1=CC=CC=C1 WPSCQFMIKNCXTH-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
GDTSJMKGXGJFGQ-UHFFFAOYSA-N 3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound O1B([O-])OB2OB([O-])OB1O2 GDTSJMKGXGJFGQ-UHFFFAOYSA-N 0.000 description 1
YSXIJTDOCXJNHI-UHFFFAOYSA-N 3-(1,2-oxazol-4-yl)propanoic acid Chemical class OC(=O)CCC=1C=NOC=1 YSXIJTDOCXJNHI-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
YBKVBBMEUKHNEB-UHFFFAOYSA-N 4-(2-methoxyphenoxy)-1-piperazin-1-ylbutan-2-ol Chemical compound COC1=CC=CC=C1OCCC(O)CN1CCNCC1 YBKVBBMEUKHNEB-UHFFFAOYSA-N 0.000 description 1
GGVADRGKHJTJIT-UHFFFAOYSA-N 4-(piperazin-1-ylmethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-oxazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NC(CN2CCNCC2)=CO1 GGVADRGKHJTJIT-UHFFFAOYSA-N 0.000 description 1
HDDFKLIJENTKQV-UHFFFAOYSA-N 4-[(2-methyl-1,3-benzothiazol-5-yl)oxy]-1-piperazin-1-ylbutan-2-ol Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCC(O)CN1CCNCC1 HDDFKLIJENTKQV-UHFFFAOYSA-N 0.000 description 1
GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
OFVIHHHWOQCWEK-UHFFFAOYSA-N 5-(chloromethyl)-3-(3-fluorophenyl)-1,2,4-oxadiazole Chemical compound FC1=CC=CC(C=2N=C(CCl)ON=2)=C1 OFVIHHHWOQCWEK-UHFFFAOYSA-N 0.000 description 1
CZMWNOPTKAFPDG-UHFFFAOYSA-N 5-(chloromethyl)-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NOC(CCl)=N1 CZMWNOPTKAFPDG-UHFFFAOYSA-N 0.000 description 1
BREDJWIGUNPOHA-UHFFFAOYSA-N 5-(oxiran-2-ylmethoxy)-2-phenyl-1,3-benzoxazole Chemical compound C1OC1COC(C=C1N=2)=CC=C1OC=2C1=CC=CC=C1 BREDJWIGUNPOHA-UHFFFAOYSA-N 0.000 description 1
ODVLVIHWERFNKW-UHFFFAOYSA-N 5-methyl-2-(oxiran-2-ylmethoxy)-1h-imidazole Chemical compound CC1=CNC(OCC2OC2)=N1 ODVLVIHWERFNKW-UHFFFAOYSA-N 0.000 description 1
IPCSVZSSVZVIGE-BFDQMJDGSA-N 5-tritiohexadecanoic acid Chemical compound C(CCCC(CCCCCCCCCCC)[3H])(=O)O IPCSVZSSVZVIGE-BFDQMJDGSA-N 0.000 description 1
BXDMUBIFFZQMQC-UHFFFAOYSA-N 6-(oxiran-2-ylmethoxy)-2-phenyl-1h-benzimidazole Chemical compound C1OC1COC(C=C1N2)=CC=C1N=C2C1=CC=CC=C1 BXDMUBIFFZQMQC-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
125000006847 BOC protecting group Chemical group 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
101710088194 Dehydrogenase Proteins 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
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
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 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229920003148 Eudragit® E polymer Polymers 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
229920001410 Microfiber Polymers 0.000 description 1
102000006404 Mitochondrial Proteins Human genes 0.000 description 1
108010058682 Mitochondrial Proteins Proteins 0.000 description 1
SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-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
229920001800 Shellac Polymers 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
229910052769 Ytterbium Inorganic materials 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
BNMGMZKOGVIDIQ-UHFFFAOYSA-N [2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=COC(C=2C=CC(=CC=2)C(F)(F)F)=N1 BNMGMZKOGVIDIQ-UHFFFAOYSA-N 0.000 description 1
FZQSLXQPHPOTHG-UHFFFAOYSA-N [K+].[K+].O1B([O-])OB2OB([O-])OB1O2 Chemical compound [K+].[K+].O1B([O-])OB2OB([O-])OB1O2 FZQSLXQPHPOTHG-UHFFFAOYSA-N 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000009471 action Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
238000007605 air drying Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
239000003708 ampul Substances 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229940127219 anticoagulant drug Drugs 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229960003121 arginine Drugs 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
238000003556 assay Methods 0.000 description 1
CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
229960003237 betaine Drugs 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 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
NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
235000001465 calcium Nutrition 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
229960003340 calcium silicate Drugs 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
229960004203 carnitine Drugs 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000013068 control sample Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
125000005266 diarylamine group Chemical group 0.000 description 1
230000035487 diastolic blood pressure Effects 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000006196 drop Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000000975 dye Substances 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
239000002662 enteric coated tablet Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
230000004129 fatty acid metabolism Effects 0.000 description 1
239000003527 fibrinolytic agent Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
238000005187 foaming Methods 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
239000000417 fungicide Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
229940014259 gelatin Drugs 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
229960002442 glucosamine Drugs 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000005241 heteroarylamino group Chemical group 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
229960002885 histidine Drugs 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
NDBQJIBNNUJNHA-UHFFFAOYSA-N hydron;methyl 2-amino-3-hydroxypropanoate;chloride Chemical compound [Cl-].COC(=O)C([NH3+])CO NDBQJIBNNUJNHA-UHFFFAOYSA-N 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002497 iodine compounds Chemical class 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 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
229960002510 mandelic acid Drugs 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
NDBQJIBNNUJNHA-DFWYDOINSA-N methyl (2s)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CO NDBQJIBNNUJNHA-DFWYDOINSA-N 0.000 description 1
ANSUDRATXSJBLY-UHFFFAOYSA-N methyl 2-amino-3-hydroxypropanoate Chemical compound COC(=O)C(N)CO ANSUDRATXSJBLY-UHFFFAOYSA-N 0.000 description 1
MCCWTHZNQPICAI-UHFFFAOYSA-N methyl 4,5-dihydro-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1COC=N1 MCCWTHZNQPICAI-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 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
239000001923 methylcellulose Substances 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000003658 microfiber Substances 0.000 description 1
210000003470 mitochondria Anatomy 0.000 description 1
230000002438 mitochondrial effect Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
MNBKLUUYKPBKDU-BBECNAHFSA-N palmitoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MNBKLUUYKPBKDU-BBECNAHFSA-N 0.000 description 1
MNBKLUUYKPBKDU-TZIIWEFPSA-N palmityl-coa Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MNBKLUUYKPBKDU-TZIIWEFPSA-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
239000000312 peanut oil Substances 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
230000002572 peristaltic effect Effects 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
229950000688 phenothiazine Drugs 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
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
BRYCUMKDWMEGMK-UHFFFAOYSA-N piperazine-2-carboxamide Chemical compound NC(=O)C1CNCCN1 BRYCUMKDWMEGMK-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 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
235000019260 propionic acid Nutrition 0.000 description 1
LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
210000003492 pulmonary vein Anatomy 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 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
229940076788 pyruvate Drugs 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
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 description 1
238000011552 rat model Methods 0.000 description 1
230000003134 recirculating effect Effects 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000002002 slurry Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000012058 sterile packaged powder Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005156 substituted alkylene group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
WGJOUDVKRXFGJF-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1OCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 WGJOUDVKRXFGJF-UHFFFAOYSA-N 0.000 description 1
JNEBBAKHBROKEQ-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-(4-methoxyphenoxy)propyl]piperazine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1OCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 JNEBBAKHBROKEQ-UHFFFAOYSA-N 0.000 description 1
XPCKEVHSXUMXRE-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-3-[(2-methyl-3H-benzimidazol-5-yl)oxy]propyl]piperazine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCN(CC1)CC(COC1=CC2=C(N=C(N2)C)C=C1)O XPCKEVHSXUMXRE-UHFFFAOYSA-N 0.000 description 1
IENFLFSMBDWJRG-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-4-(2-methoxyphenoxy)butyl]piperazine-1-carboxylate Chemical compound COC1=CC=CC=C1OCCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 IENFLFSMBDWJRG-UHFFFAOYSA-N 0.000 description 1
CMXUXPHYDAUYBY-UHFFFAOYSA-N tert-butyl 4-[2-hydroxy-4-[(2-methyl-1,3-benzothiazol-5-yl)oxy]butyl]piperazine-1-carboxylate Chemical compound C=1C=C2SC(C)=NC2=CC=1OCCC(O)CN1CCN(C(=O)OC(C)(C)C)CC1 CMXUXPHYDAUYBY-UHFFFAOYSA-N 0.000 description 1
KYAKKAMGAAUBFZ-UHFFFAOYSA-N tert-butyl 4-[3-(8-fluoronaphthalen-1-yl)oxy-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)COC1=CC=CC2=CC=CC(F)=C12 KYAKKAMGAAUBFZ-UHFFFAOYSA-N 0.000 description 1
SHNPJRUSVXSHHY-UHFFFAOYSA-N tert-butyl 4-[3-[(2-ethyl-1,3-thiazol-4-yl)oxy]-2-hydroxypropyl]piperazine-1-carboxylate Chemical compound S1C(CC)=NC(OCC(O)CN2CCN(CC2)C(=O)OC(C)(C)C)=C1 SHNPJRUSVXSHHY-UHFFFAOYSA-N 0.000 description 1
DCZJYNHYQRCTDU-UHFFFAOYSA-N tert-butyl 4-[4-(2-fluorophenoxy)-2-hydroxybutyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(O)CCOC1=CC=CC=C1F DCZJYNHYQRCTDU-UHFFFAOYSA-N 0.000 description 1
VPFVKVJOCNVUMI-UHFFFAOYSA-N tert-butyl 4-[[2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=COC(C=2C=CC(=CC=2)C(F)(F)F)=N1 VPFVKVJOCNVUMI-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000005259 triarylamine group Chemical group 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
230000004102 tricarboxylic acid cycle Effects 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
238000009777 vacuum freeze-drying Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D263/57—Aryl or substituted aryl radicals
- 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
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- A61P9/06—Antiarrhythmics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Immunology (AREA)
Hematology (AREA)
Physical Education & Sports Medicine (AREA)
Obesity (AREA)
Neurology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Dermatology (AREA)
Urology & Nephrology (AREA)
Orthopedic Medicine & Surgery (AREA)
Transplantation (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Lubricants (AREA)
Hydrogenated Pyridines (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
Paper (AREA)
Pyridine Compounds (AREA)

NO20040234A 2001-07-19 2004-01-19 Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike NO327635B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US30662101P	2001-07-19	2001-07-19
PCT/US2002/022897 WO2003008411A1 (en)	2001-07-19	2002-07-18	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors

Publications (2)

Publication Number	Publication Date
NO20040234L NO20040234L (no)	2004-03-18
NO327635B1 true NO327635B1 (no)	2009-09-07

Family

ID=23186103

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20040234A NO327635B1 (no)	2001-07-19	2004-01-19	Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike

Country Status (21)

Country	Link
US (1)	US6930111B2 (de)
EP (1)	EP1406898B1 (de)
JP (1)	JP2004537554A (de)
KR (1)	KR100919141B1 (de)
CN (1)	CN1533388A (de)
AT (1)	ATE292633T1 (de)
AU (1)	AU2008202958A1 (de)
CA (1)	CA2454059A1 (de)
DE (1)	DE60203623T2 (de)
DK (1)	DK1406898T3 (de)
ES (1)	ES2236557T3 (de)
HU (1)	HUP0402088A3 (de)
IL (1)	IL159897A0 (de)
MX (1)	MXPA04000565A (de)
NO (1)	NO327635B1 (de)
NZ (1)	NZ530705A (de)
PL (1)	PL368529A1 (de)
PT (1)	PT1406898E (de)
RU (1)	RU2300533C2 (de)
WO (1)	WO2003008411A1 (de)
ZA (1)	ZA200400404B (de)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7001909B2 (en) *	2001-07-19	2006-02-21	Cv Therapeutics, Inc.	Substituted heterocyclic compounds
AU2003248558B8 (en) *	2002-05-21	2009-07-09	Gilead Sciences, Inc.	Method of treating diabetes
US8822473B2 (en) *	2002-05-21	2014-09-02	Gilead Sciences, Inc.	Method of treating diabetes
WO2004014881A2 (en)	2002-08-09	2004-02-19	Astra Zeneca Ab	'1,2,4'oxadiazoles as modulators of metabotropic glutamate receptor-5
TW200424183A (en) *	2002-08-09	2004-11-16	Nps Pharma Inc	New compounds
US7074809B2 (en)	2002-08-09	2006-07-11	Astrazeneca Ab	Compounds
EP1806346B1 (de) *	2002-12-05	2009-07-22	Cv Therapeutics, Inc.	Substituierte Piperazinderivate und ihre Verwendung als Inhibitoren der Fettsäureoxidation
US7125876B2 (en) *	2002-12-05	2006-10-24	Cv Therapeutics, Inc.	Substituted heterocyclic compounds
ATE443058T1 (de)	2003-01-03	2009-10-15	Cv Therapeutics Inc	Substituierte heterozyklische verbindungen
KR20050092424A (ko) *	2003-01-17	2005-09-21	씨브이 쎄러퓨틱스, 인코포레이티드	심혈관 질환의 치료에 유용한 치환된 헤테로고리 화합물
WO2005000826A1 (en) *	2003-06-23	2005-01-06	Cv Therapeutics, Inc.	Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors
WO2005061470A1 (en) *	2003-12-18	2005-07-07	Cv Therapeutics, Inc.	1-akan-2-ol substituted piperazine and piperidine compounds
EP1699527A1 (de) *	2004-01-02	2006-09-13	Advanced Cardiovascular Systems, Inc.	Mit lipoprotein hoher dichte beschichtete medizinprodukte
WO2006029179A2 (en) *	2004-09-08	2006-03-16	Cv Therapeutics, Inc.	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
CA2661538A1 (en)	2006-08-24	2008-02-28	Wockhardt Research Centre	Novel macrolides and ketolides having antimicrobial activity
US8088920B2 (en) *	2008-03-31	2012-01-03	Hoffmann-La Roche Inc.	3-trifluoromethyl-pyrazine-2-carboxylic acid amide derivatives as HDL-cholesterol raising agents
WO2010042925A2 (en)	2008-10-10	2010-04-15	Vm Discovery Inc.	Compositions and methods for treating alcohol use disorders, pain and other diseases
US20100292217A1 (en) *	2009-05-14	2010-11-18	Gilead Palo Alto, Inc.	Ranolazine for the treatment of cns disorders
JPWO2011115150A1 (ja) *	2010-03-18	2013-07-04	興和株式会社	ベンゾチアジン化合物の製造方法
CN111285819A (zh) *	2018-12-07	2020-06-16	江苏恩华药业股份有限公司	一种苯并噁唑类化合物及其应用
WO2023023995A1 (zh) *	2021-08-25	2023-03-02	苏州大学	一种防治心肌缺血后心功能衰竭的药物及其应用

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1133989A (en)	1964-12-08	1968-11-20	Chugai Pharmaceutical Co Ltd	Theophylline derivatives, their salts and process for preparing the same
DE2834114A1 (de) *	1978-08-01	1980-02-14	Schering Ag	Polyalkoxyphenylpyrrolidone iii, verfahren zu ihrer herstellung und ihre verwendung
US4567264A (en)	1983-05-18	1986-01-28	Syntex (U.S.A.) Inc.	Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry
JPS6137765A (ja) *	1984-07-19	1986-02-22	サンド・アクチエンゲゼルシヤフト	３‐アミノプロポキシアリール誘導体
US4723014A (en) *	1986-11-19	1988-02-02	Warner-Lambert Company	Process for the preparation of 2-substituted-1,4-dihydropyridines
DE3723648A1 (de) *	1987-07-17	1989-01-26	Sandoz Ag	Indol-derivate, ihre herstellung und sie enthaltende arzneimittel
JPH0699399B2 (ja) *	1988-10-06	1994-12-07	三井東圧化学株式会社	新規複素環化合物およびそれを有効成分として含有する製癌剤効果増強剤
JPH02268162A (ja) *	1989-04-10	1990-11-01	Fujisawa Pharmaceut Co Ltd	ジフェニルピリジン誘導体
MX9308025A (es) *	1992-12-22	1994-08-31	Lilly Co Eli	Compuestos inhibidores de la proteasa del virus dela inmunodeficiencia humana, procedimiento para supreparacion y formulacion farmaceutica que los contiene.
WO1998021190A1 (en) *	1996-11-14	1998-05-22	American Home Products Corporation	Substituted tetrahydro-1,3,5-triazin-2[1h]-thiones as anti-atherosclerotic agents
CA2382683A1 (en) *	1999-09-13	2001-03-22	American Home Products Corporation	Glucopyranosides conjugates of 2-(4-hydroxy-phenyl)-1-¬4-(2-amin-1-yl-ethoxy)-benzyl\|-1h-indol-5-ols
SE9904765D0 (sv)	1999-12-23	1999-12-23	Astra Ab	Pharmaceutically-useful compounds
US6677343B2 (en)	2000-02-22	2004-01-13	Cv Therapeutics, Inc.	Substituted piperazine compounds
US6552023B2 (en)	2000-02-22	2003-04-22	Cv Therapeutics, Inc.	Aralkyl substituted piperazine compounds
US6451798B2 (en)	2000-02-22	2002-09-17	Cv Therapeutics, Inc.	Substituted alkyl piperazine derivatives
EP1259493A2 (de)	2000-02-22	2002-11-27	Cv Therapeutics, Inc.	Substituierte piperazin-verbindungen
AU2001239827A1 (en) *	2000-02-22	2001-09-03	Cv Therapeutics, Inc.	Substituted alkylene diamine compounds
SE0003795D0 (sv) *	2000-10-20	2000-10-20	Astrazeneca Ab	Pharmaceutically useful compounds
US6573264B1 (en)	2000-10-23	2003-06-03	Cv Therapeutics, Inc.	Heteroaryl alkyl piperazine derivatives

2002
- 2002-07-18 EP EP02756522A patent/EP1406898B1/de not_active Expired - Lifetime
- 2002-07-18 ES ES02756522T patent/ES2236557T3/es not_active Expired - Lifetime
- 2002-07-18 AT AT02756522T patent/ATE292633T1/de not_active IP Right Cessation
- 2002-07-18 IL IL15989702A patent/IL159897A0/xx unknown
- 2002-07-18 DE DE60203623T patent/DE60203623T2/de not_active Expired - Fee Related
- 2002-07-18 CA CA002454059A patent/CA2454059A1/en not_active Abandoned
- 2002-07-18 RU RU2004104951/04A patent/RU2300533C2/ru not_active IP Right Cessation
- 2002-07-18 JP JP2003513970A patent/JP2004537554A/ja not_active Ceased
- 2002-07-18 NZ NZ530705A patent/NZ530705A/en not_active IP Right Cessation
- 2002-07-18 DK DK02756522T patent/DK1406898T3/da active
- 2002-07-18 PL PL02368529A patent/PL368529A1/xx not_active Application Discontinuation
- 2002-07-18 WO PCT/US2002/022897 patent/WO2003008411A1/en not_active Ceased
- 2002-07-18 KR KR1020047000898A patent/KR100919141B1/ko not_active Expired - Fee Related
- 2002-07-18 MX MXPA04000565A patent/MXPA04000565A/es active IP Right Grant
- 2002-07-18 US US10/198,237 patent/US6930111B2/en not_active Expired - Fee Related
- 2002-07-18 HU HU0402088A patent/HUP0402088A3/hu unknown
- 2002-07-18 PT PT02756522T patent/PT1406898E/pt unknown
- 2002-07-18 CN CNA02814371XA patent/CN1533388A/zh active Pending
2004
- 2004-01-19 ZA ZA200400404A patent/ZA200400404B/en unknown
- 2004-01-19 NO NO20040234A patent/NO327635B1/no not_active IP Right Cessation
2008
- 2008-07-03 AU AU2008202958A patent/AU2008202958A1/en not_active Abandoned

Also Published As

Publication number	Publication date
WO2003008411A1 (en)	2003-01-30
EP1406898B1 (de)	2005-04-06
DK1406898T3 (da)	2005-05-30
NO20040234L (no)	2004-03-18
IL159897A0 (en)	2004-06-20
CA2454059A1 (en)	2003-01-30
NZ530705A (en)	2005-08-26
RU2300533C2 (ru)	2007-06-10
HUP0402088A3 (en)	2010-03-29
US6930111B2 (en)	2005-08-16
EP1406898A1 (de)	2004-04-14
HUP0402088A2 (hu)	2005-02-28
CN1533388A (zh)	2004-09-29
DE60203623D1 (de)	2005-05-12
ATE292633T1 (de)	2005-04-15
KR100919141B1 (ko)	2009-09-25
MXPA04000565A (es)	2005-06-17
JP2004537554A (ja)	2004-12-16
DE60203623T2 (de)	2006-01-19
PL368529A1 (en)	2005-04-04
ES2236557T3 (es)	2005-07-16
RU2004104951A (ru)	2005-06-27
AU2008202958A1 (en)	2008-07-31
HK1064374A1 (en)	2005-01-28
ZA200400404B (en)	2004-10-14
US20030181352A1 (en)	2003-09-25
PT1406898E (pt)	2005-08-31
KR20040029374A (ko)	2004-04-06
AU2002322527A2 (en)	2003-03-03
AU2002322527B2 (en)	2008-04-17

Legal Events

Date	Code	Title	Description
2011-02-28	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO327635B1 (no)	2009-09-07	Substituerte piperazinforbindelser, anvendelse derav og farmasoytisk preparat omfattende slike
US7001909B2 (en)	2006-02-21	Substituted heterocyclic compounds
US7026321B2 (en)	2006-04-11	Substituted heterocyclic compounds
US7056924B2 (en)	2006-06-06	Substituted heterocyclic compounds
AU2002322527C1 (en)	2009-02-12	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
US7271169B2 (en)	2007-09-18	Substituted heterocyclic compounds
AU2002322527A1 (en)	2003-05-22	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
HK1064374B (en)	2005-05-27	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors