HRP990054A2 - The use of 3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridine in treating heart failure - Google Patents
The use of 3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridine in treating heart failure Download PDFInfo
- Publication number
- HRP990054A2 HRP990054A2 HR60/074,934A HRP990054A HRP990054A2 HR P990054 A2 HRP990054 A2 HR P990054A2 HR P990054 A HRP990054 A HR P990054A HR P990054 A2 HRP990054 A2 HR P990054A2
- Authority
- HR
- Croatia
- Prior art keywords
- phenoxy
- trimethyl
- dimethyl
- ethyl
- pyridine
- Prior art date
Links
- 206010019280 Heart failures Diseases 0.000 title claims description 50
- VTPXXSZYQCJYRL-UHFFFAOYSA-N 3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridine Chemical compound CC1=CC(C)=CC(C)=C1OC1=NC(C)=CC=C1C VTPXXSZYQCJYRL-UHFFFAOYSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims description 75
- 239000000203 mixture Substances 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 44
- VIZBSVDBNLAVAW-UHFFFAOYSA-N 3,6-dimethyl-n-pentan-3-yl-2-(2,4,6-trimethylphenoxy)pyridin-4-amine Chemical compound CCC(CC)NC1=CC(C)=NC(OC=2C(=CC(C)=CC=2C)C)=C1C VIZBSVDBNLAVAW-UHFFFAOYSA-N 0.000 claims description 41
- ZSEJGVQTBLJRCQ-UHFFFAOYSA-N 3,6-dimethyl-4-pentan-3-yloxy-2-(2,4,6-trimethylphenoxy)pyridine Chemical compound CCC(CC)OC1=CC(C)=NC(OC=2C(=CC(C)=CC=2C)C)=C1C ZSEJGVQTBLJRCQ-UHFFFAOYSA-N 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 38
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 30
- 241000124008 Mammalia Species 0.000 claims description 25
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 18
- 239000000480 calcium channel blocker Substances 0.000 claims description 18
- 229940002612 prodrug Drugs 0.000 claims description 17
- 239000000651 prodrug Substances 0.000 claims description 17
- 241001465754 Metazoa Species 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 11
- 229960000528 amlodipine Drugs 0.000 claims description 11
- 239000005541 ACE inhibitor Substances 0.000 claims description 8
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000003451 thiazide diuretic agent Substances 0.000 claims description 7
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims description 6
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims description 6
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 6
- 229940122767 Potassium sparing diuretic Drugs 0.000 claims description 6
- 229940121792 Thiazide diuretic Drugs 0.000 claims description 6
- 229940127282 angiotensin receptor antagonist Drugs 0.000 claims description 6
- 210000000210 loop of henle Anatomy 0.000 claims description 6
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 6
- 239000003286 potassium sparing diuretic agent Substances 0.000 claims description 6
- 229940097241 potassium-sparing diuretic Drugs 0.000 claims description 6
- 229940127230 sympathomimetic drug Drugs 0.000 claims description 6
- 229940124549 vasodilator Drugs 0.000 claims description 6
- 239000003071 vasodilator agent Substances 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 claims description 5
- 229940097217 cardiac glycoside Drugs 0.000 claims description 5
- 239000002368 cardiac glycoside Substances 0.000 claims description 5
- 239000002934 diuretic Substances 0.000 claims description 5
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical group O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 claims description 5
- 229930002534 steroid glycoside Natural products 0.000 claims description 5
- 229940097420 Diuretic Drugs 0.000 claims description 4
- 230000001882 diuretic effect Effects 0.000 claims description 4
- 238000004806 packaging method and process Methods 0.000 claims description 4
- 239000002171 loop diuretic Substances 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- VCWZKGKDTSYFIG-UHFFFAOYSA-N 4-chloro-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridine Chemical compound CC1=CC(C)=CC(C)=C1OC1=NC(C)=CC(Cl)=C1C VCWZKGKDTSYFIG-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229940093499 ethyl acetate Drugs 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 3
- -1 (3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl)-(1-ethyl-propyl) Chemical group 0.000 description 3
- VUVFIQUMVQDHLS-UHFFFAOYSA-N 4-bromo-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridine Chemical compound CC1=CC(C)=CC(C)=C1OC1=NC(C)=CC(Br)=C1C VUVFIQUMVQDHLS-UHFFFAOYSA-N 0.000 description 3
- 102100021752 Corticoliberin Human genes 0.000 description 3
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 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 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- MYFIUHJIEHESCM-UHFFFAOYSA-N methyl 6-methyl-4-(pentan-3-ylamino)-2-(2,4,6-trimethylphenoxy)pyridine-3-carboxylate Chemical compound CCC(CC)NC1=CC(C)=NC(OC=2C(=CC(C)=CC=2C)C)=C1C(=O)OC MYFIUHJIEHESCM-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- BPRYUXCVCCNUFE-UHFFFAOYSA-N 2,4,6-trimethylphenol Chemical compound CC1=CC(C)=C(O)C(C)=C1 BPRYUXCVCCNUFE-UHFFFAOYSA-N 0.000 description 2
- YGUQXFNMLHUBNR-UHFFFAOYSA-N 2,4-dichloro-3,6-dimethylpyridine Chemical compound CC1=CC(Cl)=C(C)C(Cl)=N1 YGUQXFNMLHUBNR-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 2
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- GBONBLHJMVUBSJ-FAUHKOHMSA-N corticorelin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)C1=CNC=N1 GBONBLHJMVUBSJ-FAUHKOHMSA-N 0.000 description 2
- 229940041967 corticotropin-releasing hormone Drugs 0.000 description 2
- KLVRDXBAMSPYKH-RKYZNNDCSA-N corticotropin-releasing hormone (human) Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)C)C(C)C)C1=CNC=N1 KLVRDXBAMSPYKH-RKYZNNDCSA-N 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- 229960005156 digoxin Drugs 0.000 description 2
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 2
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- WMSSAJJRDQJNHG-UHFFFAOYSA-N methyl 4-chloro-6-methyl-2-(2,4,6-trimethylphenoxy)pyridine-3-carboxylate Chemical compound COC(=O)C1=C(Cl)C=C(C)N=C1OC1=C(C)C=C(C)C=C1C WMSSAJJRDQJNHG-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 2
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- WWHYJKUHEDHYST-UHFFFAOYSA-N 3,6-dimethyl-4-pentan-3-yloxy-2-(2,4,6-trimethylphenoxy)pyridin-1-ium;methanesulfonate Chemical compound CS([O-])(=O)=O.CCC(CC)OC1=CC(C)=[NH+]C(OC=2C(=CC(C)=CC=2C)C)=C1C WWHYJKUHEDHYST-UHFFFAOYSA-N 0.000 description 1
- XMUOZGAKXBMOGL-UHFFFAOYSA-N 4-hydroxy-3,6-dimethyl-1h-pyridin-2-one Chemical compound CC1=CC(O)=C(C)C(O)=N1 XMUOZGAKXBMOGL-UHFFFAOYSA-N 0.000 description 1
- LJSDPUTUULZZMP-UHFFFAOYSA-N 6-methyl-4-(pentan-3-ylamino)-2-(2,4,6-trimethylphenoxy)pyridine-3-carboxylic acid Chemical compound CCC(CC)NC1=CC(C)=NC(OC=2C(=CC(C)=CC=2C)C)=C1C(O)=O LJSDPUTUULZZMP-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000251468 Actinopterygii Species 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
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010009192 Circulatory collapse Diseases 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 101710113174 Corticoliberin Proteins 0.000 description 1
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 240000001879 Digitalis lutea Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013974 Dyspnoea paroxysmal nocturnal Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000895481 Homo sapiens Corticoliberin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034567 Peripheral circulatory failure Diseases 0.000 description 1
- 206010054048 Postoperative ileus Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 101000895495 Rattus norvegicus Corticoliberin Proteins 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 206010049771 Shock haemorrhagic Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 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
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000002026 chloroform extract Substances 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
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- LXQZBPLSOSNWJR-UHFFFAOYSA-N methyl 2,4-dichloro-6-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=C(Cl)C=C(C)N=C1Cl LXQZBPLSOSNWJR-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000002182 neurohumoral effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940097271 other diuretics in atc Drugs 0.000 description 1
- QEEJLLNYQOBRRM-KSHGRFHLSA-N ovine crf Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CN=CN1 QEEJLLNYQOBRRM-KSHGRFHLSA-N 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 206010040560 shock Diseases 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000816 toxic dose Toxicity 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
- 229960000281 trometamol Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61P9/10—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US7493498P | 1998-02-17 | 1998-02-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP990054A2 true HRP990054A2 (en) | 2000-02-29 |
Family
ID=22122537
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR60/074,934A HRP990054A2 (en) | 1998-02-17 | 1999-02-17 | The use of 3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridine in treating heart failure |
Country Status (28)
Country | Link |
---|---|
US (1) | US6043260A (is) |
EP (1) | EP0951906A1 (is) |
JP (1) | JPH11292766A (is) |
KR (1) | KR19990072616A (is) |
CN (1) | CN1231176A (is) |
AP (1) | AP9901464A0 (is) |
AR (1) | AR017723A1 (is) |
AU (1) | AU1732999A (is) |
BG (1) | BG103180A (is) |
BR (1) | BR9900653A (is) |
CA (1) | CA2262252C (is) |
EA (1) | EA199900124A3 (is) |
GT (1) | GT199900015A (is) |
HR (1) | HRP990054A2 (is) |
HU (1) | HUP9900386A3 (is) |
ID (1) | ID23218A (is) |
IL (1) | IL128531A0 (is) |
IS (1) | IS4975A (is) |
MA (1) | MA26608A1 (is) |
NO (1) | NO990722L (is) |
OA (1) | OA10976A (is) |
PA (1) | PA8467401A1 (is) |
PE (1) | PE20000266A1 (is) |
PL (1) | PL331507A1 (is) |
SG (1) | SG81261A1 (is) |
TN (1) | TNSN99024A1 (is) |
TR (1) | TR199900328A2 (is) |
ZA (1) | ZA991220B (is) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6956047B1 (en) | 1995-06-06 | 2005-10-18 | Pfizer Inc. | Corticotropin releasing factor antagonists |
US7067664B1 (en) | 1995-06-06 | 2006-06-27 | Pfizer Inc. | Corticotropin releasing factor antagonists |
US6403599B1 (en) | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
US6387894B1 (en) * | 1999-06-11 | 2002-05-14 | Pfizer Inc. | Use of CRF antagonists and renin-angiotensin system inhibitors |
EP1216037A2 (en) | 1999-09-21 | 2002-06-26 | Emory University | Methods and compositions for treating platelet-related disorders using mpl pathway inhibitory agents |
BR0107662A (pt) * | 2000-01-18 | 2002-11-19 | Pfizer Prod Inc | Antagonistas do fator de liberação de corticotropina |
US6737430B2 (en) | 2000-11-09 | 2004-05-18 | Pfizer, Inc. | Mutual prodrug of amlodipine and atorvastatin |
GB0027410D0 (en) * | 2000-11-09 | 2000-12-27 | Pfizer Ltd | Mutual prodrug of amlodipine and atorvastatin |
US6992087B2 (en) | 2001-11-21 | 2006-01-31 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
US7015229B2 (en) | 2002-02-22 | 2006-03-21 | Pfizer Inc | Substituted pyrimidinones and pyrimidinthiones |
CA2478715A1 (en) * | 2002-03-13 | 2003-09-25 | Pharmacia & Upjohn Company | Novel pyrazolo [1,5-a]pyridine derivatives and their use as neurotransmitter modulators |
JP2005533014A (ja) * | 2002-04-26 | 2005-11-04 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 置換ピラジン誘導体 |
MXPA05002418A (es) * | 2002-09-12 | 2005-05-27 | Pharmacia & Upjohn Co Llc | Derivados de 1,4-pirazina sustituidos. |
AR041470A1 (es) * | 2002-10-17 | 2005-05-18 | Upjohn Co | Compuestos de pirrolo (1,2 - b) piridazina y sus usos |
MXPA05005408A (es) * | 2002-11-21 | 2005-08-03 | Pharmacia & Upjohn Co Llc | Compuestos de pirazina como moduladores de factor de liberacion de corticotropina. |
WO2004094408A1 (en) * | 2003-04-23 | 2004-11-04 | Pharmacia & Upjohn Company Llc | Substituted pyrimidinones and pyrimidinthiones as crf antagonists |
CA2523072A1 (en) * | 2003-05-07 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Pyrrolo (1,2-b) pyridazine compounds and their use as crf-1 receptor antagonists |
JP2006525989A (ja) * | 2003-05-09 | 2006-11-16 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | Cns障害を治療するためのcrf1受容体アンタゴニストとしてのピラジノン |
CA2524352A1 (en) * | 2003-05-09 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Substituted pyrimidine derivatives |
CA2524519A1 (en) * | 2003-05-09 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Compounds as crf1 receptor antagonists |
US20050209289A1 (en) * | 2004-03-16 | 2005-09-22 | Talarico Matthew T | Method for vascular dysregulation |
US20060211710A1 (en) * | 2005-03-17 | 2006-09-21 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
US8338441B2 (en) | 2009-05-15 | 2012-12-25 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW574214B (en) * | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
US6403599B1 (en) * | 1995-11-08 | 2002-06-11 | Pfizer Inc | Corticotropin releasing factor antagonists |
EP0795327A1 (en) * | 1996-03-13 | 1997-09-17 | Pfizer Inc. | Use of Amlodipine for the treatment and prophylaxis of congestive cardiac failure of non-ischaemic origin |
-
1999
- 1999-01-18 PA PA19998467401A patent/PA8467401A1/es unknown
- 1999-02-02 GT GT199900015A patent/GT199900015A/es unknown
- 1999-02-10 SG SG9900526A patent/SG81261A1/en unknown
- 1999-02-10 US US09/248,073 patent/US6043260A/en not_active Expired - Fee Related
- 1999-02-11 EP EP99301006A patent/EP0951906A1/en not_active Withdrawn
- 1999-02-11 AP APAP/P/1999/001464A patent/AP9901464A0/en unknown
- 1999-02-11 IS IS4975A patent/IS4975A/is unknown
- 1999-02-11 CN CN99102122A patent/CN1231176A/zh active Pending
- 1999-02-12 PE PE1999000127A patent/PE20000266A1/es not_active Application Discontinuation
- 1999-02-12 KR KR1019990004934A patent/KR19990072616A/ko not_active Application Discontinuation
- 1999-02-12 BR BR9900653-7A patent/BR9900653A/pt not_active Application Discontinuation
- 1999-02-15 IL IL12853199A patent/IL128531A0/xx unknown
- 1999-02-15 CA CA002262252A patent/CA2262252C/en not_active Expired - Fee Related
- 1999-02-15 ID IDP990113D patent/ID23218A/id unknown
- 1999-02-16 MA MA25465A patent/MA26608A1/fr unknown
- 1999-02-16 AU AU17329/99A patent/AU1732999A/en not_active Abandoned
- 1999-02-16 TN TNTNSN99024A patent/TNSN99024A1/fr unknown
- 1999-02-16 NO NO990722A patent/NO990722L/no unknown
- 1999-02-16 TR TR1999/00328A patent/TR199900328A2/xx unknown
- 1999-02-16 ZA ZA9901220A patent/ZA991220B/xx unknown
- 1999-02-16 HU HU9900386A patent/HUP9900386A3/hu unknown
- 1999-02-16 AR ARP990100619A patent/AR017723A1/es unknown
- 1999-02-16 BG BG103180A patent/BG103180A/bg unknown
- 1999-02-16 JP JP11037464A patent/JPH11292766A/ja active Pending
- 1999-02-16 EA EA199900124A patent/EA199900124A3/ru unknown
- 1999-02-16 OA OA9900034A patent/OA10976A/en unknown
- 1999-02-17 PL PL99331507A patent/PL331507A1/xx unknown
- 1999-02-17 HR HR60/074,934A patent/HRP990054A2/hr not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
AR017723A1 (es) | 2001-09-12 |
CA2262252C (en) | 2006-01-10 |
TNSN99024A1 (fr) | 2005-11-10 |
HUP9900386A2 (hu) | 1999-11-29 |
EP0951906A1 (en) | 1999-10-27 |
US6043260A (en) | 2000-03-28 |
PL331507A1 (en) | 1999-08-30 |
PE20000266A1 (es) | 2000-04-07 |
JPH11292766A (ja) | 1999-10-26 |
BG103180A (bg) | 1999-09-30 |
EA199900124A3 (ru) | 1999-12-29 |
CN1231176A (zh) | 1999-10-13 |
HU9900386D0 (en) | 1999-04-28 |
SG81261A1 (en) | 2001-06-19 |
GT199900015A (es) | 2000-07-26 |
OA10976A (en) | 2001-11-05 |
EA199900124A2 (ru) | 1999-08-26 |
BR9900653A (pt) | 2000-10-17 |
MA26608A1 (fr) | 2004-12-20 |
NO990722D0 (no) | 1999-02-16 |
ZA991220B (en) | 2000-08-16 |
IS4975A (is) | 1999-08-18 |
PA8467401A1 (es) | 2000-09-29 |
IL128531A0 (en) | 2000-01-31 |
HUP9900386A3 (en) | 1999-12-28 |
TR199900328A2 (xx) | 1999-10-21 |
ID23218A (id) | 2000-03-30 |
NO990722L (no) | 1999-08-18 |
KR19990072616A (ko) | 1999-09-27 |
AU1732999A (en) | 1999-09-02 |
AP9901464A0 (en) | 1999-03-31 |
CA2262252A1 (en) | 1999-08-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP990054A2 (en) | The use of 3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridine in treating heart failure | |
US4666908A (en) | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use | |
EA015516B1 (ru) | Ингибиторы 11-бета-гидроксистероид дегидрогеназы 1 | |
DE60108633T2 (de) | 1,3-dihydro-2h-indol-2-on derivate und deren verwendung als liganden der arginin-vasopressin v1b und v1a rezeptoren | |
JPS62281858A (ja) | ピペリジン誘導体及びその類縁誘導体 | |
WO2011160548A1 (zh) | 2-芳基咪唑并[1,2-a]吡啶-3-乙酰胺衍生物、其制备方法及用途 | |
JP4571863B2 (ja) | 抗痛覚過敏剤として有用なキナゾリノン誘導体 | |
US20130040988A1 (en) | 3-amino-pyridine derivatives for the treatment of metabolic disorders | |
US4769384A (en) | Benzimidazole derivatives | |
JP2002326983A (ja) | β3アゴニスト及びその使用 | |
JP2007522095A (ja) | ジプラシドンを用いた不安の治療 | |
JPS59216877A (ja) | 置換フエニル−2−(1h)−ピリミジノン | |
JP2726999B2 (ja) | イミダゾ[2,1−b]ベンゾチアゾール誘導体及び該化合物を有効成分とする抗潰瘍剤 | |
JPH03169862A (ja) | 新規ピリジン誘導体、それらを含む製薬組成物、およびその製造方法 | |
JPS61238786A (ja) | ピリジン誘導体 | |
JPH0377191B2 (is) | ||
DE69008565T2 (de) | Aminoalkoxyphenyl-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Zusammensetzungen. | |
JP2005526113A (ja) | 新規なピペリジニル−アルキルアミノ−ピリダジノン誘導体、その製法及びこの化合物を含有する医薬組成物 | |
CZ51399A3 (cs) | Farmaceutická kompozice a kit | |
JPH05504778A (ja) | 新規3(2h)―ピリダジノン、それを含む医薬組成物及びその調製方法 | |
JPH0770083A (ja) | イミダゾール誘導体を有効成分とする血圧降下剤 | |
JPH05213885A (ja) | デカヒドロキノリンの新規な誘導体、それらの製造法、製造中間体、それらの薬剤としての用途及びそれらを含有する組成物 | |
JPS62240677A (ja) | カルボスチリル誘導体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20000217 Year of fee payment: 2 |
|
A1OB | Publication of a patent application | ||
OBST | Application withdrawn |