ZA200305414B - Acylated 6, 7, 8, 9-tetrahydro-5H-benzocycloheptenyl amines and their use as pharmaceutical. - Google Patents
Acylated 6, 7, 8, 9-tetrahydro-5H-benzocycloheptenyl amines and their use as pharmaceutical. Download PDFInfo
- Publication number
- ZA200305414B ZA200305414B ZA200305414A ZA200305414A ZA200305414B ZA 200305414 B ZA200305414 B ZA 200305414B ZA 200305414 A ZA200305414 A ZA 200305414A ZA 200305414 A ZA200305414 A ZA 200305414A ZA 200305414 B ZA200305414 B ZA 200305414B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- group
- phenyl
- heteroaryl
- substituents
- Prior art date
Links
- -1 6, 7, 8, 9-tetrahydro-5H-benzocycloheptenyl amines Chemical class 0.000 title claims description 266
- 125000001424 substituent group Chemical group 0.000 claims description 161
- 229910052736 halogen Inorganic materials 0.000 claims description 100
- 150000002367 halogens Chemical class 0.000 claims description 100
- 125000001072 heteroaryl group Chemical group 0.000 claims description 93
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 90
- 150000001875 compounds Chemical class 0.000 claims description 78
- 125000002577 pseudohalo group Chemical group 0.000 claims description 76
- 229910052799 carbon Inorganic materials 0.000 claims description 72
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 150000001412 amines Chemical class 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 229910052731 fluorine Inorganic materials 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 10
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 230000003511 endothelial effect Effects 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 6
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 230000014509 gene expression Effects 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000007903 gelatin capsule Substances 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- AVYNORNFILBJTK-UHFFFAOYSA-N 2-methyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)-3h-benzimidazole-5-carboxamide Chemical compound C1CCC2=CC=CC=C2CC1NC(=O)C1=CC=C(NC(C)=N2)C2=C1 AVYNORNFILBJTK-UHFFFAOYSA-N 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 208000002249 Diabetes Complications Diseases 0.000 claims description 3
- 206010048554 Endothelial dysfunction Diseases 0.000 claims description 3
- 208000007718 Stable Angina Diseases 0.000 claims description 3
- 239000008298 dragée Substances 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 230000008694 endothelial dysfunction Effects 0.000 claims description 3
- 239000007943 implant Substances 0.000 claims description 3
- 238000001802 infusion Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003094 microcapsule Substances 0.000 claims description 3
- 239000007922 nasal spray Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 239000007940 sugar coated tablet Substances 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- 239000006188 syrup Substances 0.000 claims description 3
- 235000020357 syrup Nutrition 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 2
- SGMNKIYUPGAEHW-UHFFFAOYSA-N 2,6-dimethyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyridine-3-carboxamide Chemical compound CC1=NC(C)=CC=C1C(=O)NC1CC2=CC=CC=C2CCC1 SGMNKIYUPGAEHW-UHFFFAOYSA-N 0.000 claims description 2
- UZSAQBDSLGCAGH-UHFFFAOYSA-N 2-amino-6-chloro-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyridine-3-carboxamide Chemical compound NC1=NC(Cl)=CC=C1C(=O)NC1CC2=CC=CC=C2CCC1 UZSAQBDSLGCAGH-UHFFFAOYSA-N 0.000 claims description 2
- CNPROWSZFLRYJA-UHFFFAOYSA-N 2-amino-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyridine-3-carboxamide Chemical compound NC1=NC=CC=C1C(=O)NC1CC2=CC=CC=C2CCC1 CNPROWSZFLRYJA-UHFFFAOYSA-N 0.000 claims description 2
- CFXZFMJPGVBGQZ-UHFFFAOYSA-N 3-amino-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrazine-2-carboxamide Chemical compound NC1=NC=CN=C1C(=O)NC1CC2=CC=CC=C2CCC1 CFXZFMJPGVBGQZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- QCNJNGNTRWMPNN-UHFFFAOYSA-N 4-fluoro-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC1CC2=CC=CC=C2CCC1 QCNJNGNTRWMPNN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 claims description 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 2
- 208000007530 Essential hypertension Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 201000001068 Prinzmetal angina Diseases 0.000 claims description 2
- 201000003099 Renovascular Hypertension Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 201000004239 Secondary hypertension Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims description 2
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 230000007882 cirrhosis Effects 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 229940124558 contraceptive agent Drugs 0.000 claims description 2
- 239000003433 contraceptive agent Substances 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 238000007306 functionalization reaction Methods 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 201000001881 impotence Diseases 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 230000007334 memory performance Effects 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 claims 1
- ONOOGYUYUYRXNQ-UHFFFAOYSA-N 2,5-dimethyl-1-(pyridin-4-ylmethyl)-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrrole-3-carboxamide Chemical compound CC1=CC(C(=O)NC2CC3=CC=CC=C3CCC2)=C(C)N1CC1=CC=NC=C1 ONOOGYUYUYRXNQ-UHFFFAOYSA-N 0.000 claims 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- PSXTUQVQRMXQNR-UHFFFAOYSA-N 3-amino-5,6-dimethylpyrazine-2-carboxylic acid Chemical compound CC1=NC(N)=C(C(O)=O)N=C1C PSXTUQVQRMXQNR-UHFFFAOYSA-N 0.000 claims 1
- IPGHOIXQBNZIBN-UHFFFAOYSA-N 3-amino-5-methyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrazine-2-carboxamide Chemical compound NC1=NC(C)=CN=C1C(=O)NC1CC2=CC=CC=C2CCC1 IPGHOIXQBNZIBN-UHFFFAOYSA-N 0.000 claims 1
- MRGLZNLNWSFZRY-UHFFFAOYSA-N 3-pyrrolidin-1-yl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)benzamide Chemical compound C1CCC2=CC=CC=C2CC1NC(=O)C(C=1)=CC=CC=1N1CCCC1 MRGLZNLNWSFZRY-UHFFFAOYSA-N 0.000 claims 1
- ZBWGONUZQCSCOO-UHFFFAOYSA-N 5-methyl-1-phenyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrazole-4-carboxamide Chemical compound CC1=C(C(=O)NC2CC3=CC=CC=C3CCC2)C=NN1C1=CC=CC=C1 ZBWGONUZQCSCOO-UHFFFAOYSA-N 0.000 claims 1
- DKVHOEYPLXMCKN-UHFFFAOYSA-N 5-methyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrazine-2-carboxamide Chemical compound C1=NC(C)=CN=C1C(=O)NC1CC2=CC=CC=C2CCC1 DKVHOEYPLXMCKN-UHFFFAOYSA-N 0.000 claims 1
- FUXGIWUFWCCHHY-UHFFFAOYSA-N 6-pyrrolidin-1-yl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyridine-3-carboxamide Chemical compound C1CCC2=CC=CC=C2CC1NC(=O)C(C=N1)=CC=C1N1CCCC1 FUXGIWUFWCCHHY-UHFFFAOYSA-N 0.000 claims 1
- 239000000443 aerosol Substances 0.000 claims 1
- 239000007822 coupling agent Substances 0.000 claims 1
- 229940097496 nasal spray Drugs 0.000 claims 1
- 230000000638 stimulation Effects 0.000 claims 1
- 229940098465 tincture Drugs 0.000 claims 1
- 230000014759 maintenance of location Effects 0.000 description 60
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 38
- 229960003966 nicotinamide Drugs 0.000 description 14
- 239000011570 nicotinamide Substances 0.000 description 14
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229920000728 polyester Polymers 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 210000003038 endothelium Anatomy 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- GWRSATNRNFYMDI-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound FC=1C=C(NC=2N=C3N(C4CCCC4)CC(F)(F)C(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 GWRSATNRNFYMDI-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000004450 alkenylene group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine 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
- 125000000524 functional group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- MQGBARXPCXAFRZ-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-carboxylic acid Chemical compound CC1=NC(C)=C(C(O)=O)S1 MQGBARXPCXAFRZ-UHFFFAOYSA-N 0.000 description 2
- VDVWTJFVFQVCFN-UHFFFAOYSA-N 2,5-dimethyl-1h-pyrrole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=C(C)N1 VDVWTJFVFQVCFN-UHFFFAOYSA-N 0.000 description 2
- PNXJWEQRIVLWBG-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1C(F)(F)F PNXJWEQRIVLWBG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- VUWIQUHYWDRRGC-UHFFFAOYSA-N 3-amino-5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C(N)=N1 VUWIQUHYWDRRGC-UHFFFAOYSA-N 0.000 description 2
- ZAGZIOYVEIDDJA-UHFFFAOYSA-N 3-aminopyrazine-2-carboxylic acid Chemical compound NC1=NC=CN=C1C(O)=O ZAGZIOYVEIDDJA-UHFFFAOYSA-N 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- USSMIQWDLWJQDQ-UHFFFAOYSA-N 5-methyl-1-phenylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C1=CC=CC=C1 USSMIQWDLWJQDQ-UHFFFAOYSA-N 0.000 description 2
- RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 description 2
- MDVRGZASGHPBAG-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-amine Chemical compound C1C(N)CCCC2=CC=CC=C21 MDVRGZASGHPBAG-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229920000180 alkyd Polymers 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 230000036523 atherogenesis Effects 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000005549 heteroarylene group Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000004957 naphthylene group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229930192474 thiophene Natural products 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
- 125000003944 tolyl group Chemical group 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- MDVRGZASGHPBAG-NSHDSACASA-N (6s)-6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-amine Chemical compound C1[C@@H](N)CCCC2=CC=CC=C21 MDVRGZASGHPBAG-NSHDSACASA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- HTJMXYRLEDBSLT-UHFFFAOYSA-N 1,2,4,5-tetrazine Chemical compound C1=NN=CN=N1 HTJMXYRLEDBSLT-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- JUYWDXUELATAOI-UHFFFAOYSA-N 1,3-oxazepine Chemical compound O1C=CC=CN=C1 JUYWDXUELATAOI-UHFFFAOYSA-N 0.000 description 1
- SIMIXFVGSWZJJV-UHFFFAOYSA-N 1,3-thiazepine Chemical compound S1C=CC=CN=C1 SIMIXFVGSWZJJV-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- SMPJBTIFNUUWGQ-UHFFFAOYSA-N 1-phenyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound FC(F)(F)C1=C(C(=O)O)C=NN1C1=CC=CC=C1 SMPJBTIFNUUWGQ-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 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
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 1
- ROGHUJUFCRFUSO-UHFFFAOYSA-N 1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CN2 ROGHUJUFCRFUSO-UHFFFAOYSA-N 0.000 description 1
- FEFGZJBHDQRFOS-UHFFFAOYSA-N 2,4-dimethylpyrimidine-5-carboxylic acid Chemical compound CC1=NC=C(C(O)=O)C(C)=N1 FEFGZJBHDQRFOS-UHFFFAOYSA-N 0.000 description 1
- IHQUENCAKSKBOG-UHFFFAOYSA-N 2,5-dimethyl-1-(pyridin-4-ylmethyl)pyrrole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=C(C)N1CC1=CC=NC=C1 IHQUENCAKSKBOG-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- GZHWABCBKGMLIE-UHFFFAOYSA-N 2-methyl-3h-benzimidazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(C)=NC2=C1 GZHWABCBKGMLIE-UHFFFAOYSA-N 0.000 description 1
- AVYNORNFILBJTK-KRWDZBQOSA-N 2-methyl-n-[(6s)-6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl]-3h-benzimidazole-5-carboxamide Chemical compound C1CCC2=CC=CC=C2C[C@H]1NC(=O)C1=CC=C2N=C(C)NC2=C1 AVYNORNFILBJTK-KRWDZBQOSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 description 1
- KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 1
- NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 1
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
- ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 1
- GUOVBFFLXKJFEE-UHFFFAOYSA-N 2h-benzotriazole-5-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NNN=C21 GUOVBFFLXKJFEE-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- MITXLYNRFCATDU-UHFFFAOYSA-N 3-amino-5,6-dimethyl-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyrazine-2-carboxamide Chemical compound N1=C(C)C(C)=NC(N)=C1C(=O)NC1CC2=CC=CC=C2CCC1 MITXLYNRFCATDU-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WOXWWNLYVJKNTC-UHFFFAOYSA-N 4-amino-2-pyridin-3-ylpyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(N)=NC(C=2C=NC=CC=2)=N1 WOXWWNLYVJKNTC-UHFFFAOYSA-N 0.000 description 1
- YERXFQDSPYCZOP-UHFFFAOYSA-N 4-amino-2-pyridin-4-ylpyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(N)=NC(C=2C=CN=CC=2)=N1 YERXFQDSPYCZOP-UHFFFAOYSA-N 0.000 description 1
- CRSMRBYEBHOYRM-UHFFFAOYSA-N 4-methyl-2-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(O)=O)=C(C)N=C1C1=CC=CC=C1 CRSMRBYEBHOYRM-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- BFMGSMOYBHOHGI-UHFFFAOYSA-N 5-amino-1-phenylpyrazole-4-carboxylic acid Chemical compound NC1=C(C(O)=O)C=NN1C1=CC=CC=C1 BFMGSMOYBHOHGI-UHFFFAOYSA-N 0.000 description 1
- KWHUHTFXMNQHAA-UHFFFAOYSA-N 6,7,8,9-tetrahydrobenzo[7]annulen-5-one Chemical compound O=C1CCCCC2=CC=CC=C12 KWHUHTFXMNQHAA-UHFFFAOYSA-N 0.000 description 1
- GHSOGAWYQSTDAJ-UHFFFAOYSA-N 6-amino-6,7,8,9-tetrahydro-5h-benzo[7]annulen-5-ol Chemical compound OC1C(N)CCCC2=CC=CC=C21 GHSOGAWYQSTDAJ-UHFFFAOYSA-N 0.000 description 1
- LGDKWLPTGZRTAA-UHFFFAOYSA-N 6-methyl-2-(methylamino)-n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)pyridine-3-carboxamide Chemical compound CNC1=NC(C)=CC=C1C(=O)NC1CC2=CC=CC=C2CCC1 LGDKWLPTGZRTAA-UHFFFAOYSA-N 0.000 description 1
- HXPHLYQBFPDHNK-UHFFFAOYSA-N 6-pyrrolidin-1-ylpyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(N2CCCC2)=N1 HXPHLYQBFPDHNK-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 241000854350 Enicospilus group Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 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
- 239000007821 HATU Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 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 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 101100080274 Mus musculus Nos3 gene Proteins 0.000 description 1
- HXQXTHQEESRMNE-UHFFFAOYSA-N N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-yl)-3H-benzimidazole-5-carboxamide Chemical compound C1=CC=CC2=C1CCCC(C2)NC(=O)C1=CC2=C(N=CN2)C=C1 HXQXTHQEESRMNE-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005082 alkoxyalkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 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
- 125000005569 butenylene group Chemical group 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
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000005020 hydroxyalkenyl group Chemical group 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 1
- 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 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
- 230000003993 interaction Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- JTEUAQLTMFIFGG-UHFFFAOYSA-N n-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-6-yl)-1h-indole-6-carboxamide Chemical compound C1CCC2=CC=CC=C2CC1NC(=O)C1=CC=C(C=CN2)C2=C1 JTEUAQLTMFIFGG-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 125000001400 nonyl 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])[H] 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 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
- 230000007170 pathology Effects 0.000 description 1
- 230000004796 pathophysiological change Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 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
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 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
- 230000007115 recruitment Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
- 229960004617 sapropterin Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001308 synthesis method Methods 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000001196 vasorelaxation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/54—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/67—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/74—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/12—One of the condensed rings being a six-membered aromatic ring the other ring being at least seven-membered
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01102853 | 2001-02-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200305414B true ZA200305414B (en) | 2004-05-20 |
Family
ID=8176424
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200305414A ZA200305414B (en) | 2001-02-13 | 2003-07-14 | Acylated 6, 7, 8, 9-tetrahydro-5H-benzocycloheptenyl amines and their use as pharmaceutical. |
Country Status (33)
Country | Link |
---|---|
US (2) | US6759412B2 (es) |
EP (1) | EP1362027B1 (es) |
JP (1) | JP4319836B2 (es) |
KR (1) | KR100975781B1 (es) |
CN (1) | CN1296346C (es) |
AR (1) | AR035431A1 (es) |
AT (1) | ATE396171T1 (es) |
AU (1) | AU2002253012B2 (es) |
BG (1) | BG108060A (es) |
BR (1) | BR0207197A (es) |
CA (1) | CA2438324C (es) |
CZ (1) | CZ20032134A3 (es) |
DE (1) | DE60226704D1 (es) |
DK (1) | DK1362027T3 (es) |
EE (1) | EE200300370A (es) |
ES (1) | ES2304432T3 (es) |
HK (1) | HK1061017A1 (es) |
HR (1) | HRP20030645A2 (es) |
HU (1) | HUP0303133A3 (es) |
IL (2) | IL157211A0 (es) |
MX (1) | MXPA03006893A (es) |
MY (1) | MY136316A (es) |
NO (1) | NO328767B1 (es) |
NZ (1) | NZ527471A (es) |
PE (1) | PE20020870A1 (es) |
PL (1) | PL363639A1 (es) |
PT (1) | PT1362027E (es) |
RU (1) | RU2301797C2 (es) |
SK (1) | SK10092003A3 (es) |
UY (1) | UY27165A1 (es) |
WO (1) | WO2002064546A2 (es) |
YU (1) | YU64203A (es) |
ZA (1) | ZA200305414B (es) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020147198A1 (en) * | 2001-01-12 | 2002-10-10 | Guoqing Chen | Substituted arylamine derivatives and methods of use |
US20030134836A1 (en) | 2001-01-12 | 2003-07-17 | Amgen Inc. | Substituted arylamine derivatives and methods of use |
TWI241190B (en) * | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
PE20020870A1 (es) * | 2001-02-13 | 2002-11-18 | Aventis Pharma Gmbh | 6,7,8,9-tetrahidro-5h-benzocicloheptenil aminas aciladas |
TWI243164B (en) * | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
US7176310B1 (en) * | 2002-04-09 | 2007-02-13 | Ucb Sa | Pyrimidinecarboxamide derivatives and their use as anti-inflammatory agents |
US7105513B2 (en) * | 2002-08-07 | 2006-09-12 | Sanofi-Avertis Deutschland Gmbh | Acylated, heteroaryl-condensed cycloalkenylamines and their use as pharmaceuticals |
EP1388342A1 (en) * | 2002-08-07 | 2004-02-11 | Aventis Pharma Deutschland GmbH | Acylated, heteroaryl-condensed cycloalkenylamines and their use as pharmaceuticals |
US7186735B2 (en) | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
US7338956B2 (en) | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
US7132536B2 (en) * | 2003-04-24 | 2006-11-07 | Sanofi-Aventis Deutschland Gmbh | Triaza- and tetraaza-anthracenedione derivatives, their preparation and their use as pharmaceuticals |
AU2004261250B2 (en) | 2003-07-29 | 2009-02-26 | Xenon Pharmaceuticals Inc. | Pyridyl derivatives and their use as therapeutic agents |
EP1529525A1 (en) * | 2003-11-06 | 2005-05-11 | Aventis Pharma Deutschland GmbH | ENOS transcription enhancers for use in the cell therapy of ischemic heart diseases |
US8309608B2 (en) * | 2003-11-06 | 2012-11-13 | Sanofi-Aventis Deutschland Gmbh | Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases |
EP1568698A1 (en) | 2004-02-27 | 2005-08-31 | Aventis Pharma Deutschland GmbH | Pyrrole-derivatives as factor Xa inhibitors |
JP2007277096A (ja) * | 2004-07-15 | 2007-10-25 | Astellas Pharma Inc | フェネチルニコチンアミド誘導体含有医薬 |
US7696202B2 (en) * | 2004-11-10 | 2010-04-13 | Synta Pharmaceuticals Corp. | IL-12 modulatory compounds |
US7365061B2 (en) | 2004-11-15 | 2008-04-29 | Bristol-Myers Squibb Company | 2-Amino-3-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
WO2006053274A2 (en) | 2004-11-15 | 2006-05-18 | Bristol-Myers Squibb Company | 2-amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
US7226942B2 (en) | 2004-11-15 | 2007-06-05 | Bristol-Myers Squibb Company | 2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
US7223786B2 (en) | 2004-11-15 | 2007-05-29 | Bristol-Myers Squibb Company | 2-aminonaphthalene derivatives and related glycogen phosphorylase inhibitors |
EP1741709A1 (en) | 2005-06-28 | 2007-01-10 | Sanofi-Aventis Deutschland GmbH | Heteroaryl-substituted amides comprising a saturated linker group, and their use as pharmaceuticals |
EP1741708A1 (en) | 2005-06-28 | 2007-01-10 | Sanofi-Aventis Deutschland GmbH | Heteroaryl-substituted amides comprising an unsaturated or cyclic linker group, and their use as pharmaceuticals |
CN101405270B (zh) | 2006-03-22 | 2013-01-16 | 霍夫曼-拉罗奇有限公司 | 作为11-β-HSD-1的吡唑类 |
EP1905764A1 (en) | 2006-09-30 | 2008-04-02 | Sanofi-Aventis | Substituted 2-Phenyl-benzimidazoles and their use as pharmaceuticals |
EP1923062A1 (en) | 2006-11-16 | 2008-05-21 | sanofi-aventis | Imidazo[2,1-b]thiazoles and their use as pharmaceuticals |
EP1939180A1 (en) | 2006-12-20 | 2008-07-02 | sanofi-aventis | Heteroarylacrylamides and their use as pharmaceuticals for the stimulation of the expression of endothelial NO synthase |
EP1942104A1 (en) | 2006-12-20 | 2008-07-09 | sanofi-aventis | Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals |
EP1939181A1 (en) * | 2006-12-27 | 2008-07-02 | sanofi-aventis | Heteroaryl-substituted carboxamides and use thereof for the stimulation of the expression of NO synthase |
EP1964841A1 (en) | 2007-02-28 | 2008-09-03 | sanofi-aventis | Imidazo[1,2-a]azine and their use as pharmaceuticals |
EP1964840A1 (en) | 2007-02-28 | 2008-09-03 | sanofi-aventis | Imidazo[1,2-a]pyridines and their use as pharmaceuticals |
WO2011115804A1 (en) | 2010-03-17 | 2011-09-22 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
KR101813931B1 (ko) | 2010-06-30 | 2018-01-02 | 아이언우드 파마슈티컬스, 인코포레이티드 | Sgc 자극제 |
RU2582679C2 (ru) | 2010-11-09 | 2016-04-27 | Айронвуд Фармасьютикалз, Инк. | СТИМУЛЯТОРЫ sGC |
US20120309796A1 (en) * | 2011-06-06 | 2012-12-06 | Fariborz Firooznia | Benzocycloheptene acetic acids |
US9139564B2 (en) | 2011-12-27 | 2015-09-22 | Ironwood Pharmaceuticals, Inc. | 2-benzyl, 3-(pyrimidin-2-yl) substituted pyrazoles useful as sGC stimulators |
WO2014047111A1 (en) | 2012-09-18 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2014047325A1 (en) | 2012-09-19 | 2014-03-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
CN110016020B (zh) | 2013-03-15 | 2022-07-26 | 赛克里翁治疗有限公司 | 化合物或其药学上可接受的盐及其应用和药物组合物 |
KR101938451B1 (ko) * | 2013-06-03 | 2019-01-14 | 마빈 새크너 | 수동적 모의 조깅 장치 |
CA2933250A1 (en) | 2013-12-11 | 2015-06-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
WO2015106268A1 (en) | 2014-01-13 | 2015-07-16 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
CA2959757A1 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | Pyrazole derivatives as sgc stimulators |
WO2016044445A2 (en) | 2014-09-17 | 2016-03-24 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
EP3194386A2 (en) | 2014-09-17 | 2017-07-26 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
CN109563087A (zh) | 2016-07-07 | 2019-04-02 | 铁木医药有限公司 | sGC刺激剂的固体形式 |
AU2017291826B2 (en) | 2016-07-07 | 2021-10-21 | Cyclerion Therapeutics, Inc. | Phosphorus prodrugs of sGC stimulators |
WO2024091983A1 (en) * | 2022-10-25 | 2024-05-02 | Artus Therapeutics, Inc. | Therapeutic agents for enhancing epithelial and/or endothelial barrier function |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU8402275A (en) * | 1974-08-26 | 1977-02-17 | Takeda Chemical Industries Ltd | Benzocycloheptene derivatives |
DE3807813A1 (de) | 1988-03-10 | 1989-09-21 | Thomae Gmbh Dr K | Neue benzocycloheptenderivate, diese verbindungen enthaltende arzneimittel und verfahren zu deren herstellung |
KR970706272A (ko) | 1995-08-10 | 1997-11-03 | 클래스 빌헬름슨 | 치료에 유용한 바이시클릭 아미딘 유도체(Bicyclic Amidine Derivatives Useful in Therapy) |
US6180597B1 (en) | 1998-03-19 | 2001-01-30 | Brigham And Women's Hospital, Inc. | Upregulation of Type III endothelial cell nitric oxide synthase by rho GTPase function inhibitors |
WO2000003746A2 (en) * | 1998-07-14 | 2000-01-27 | The Brigham And Women's Hospital, Inc. | Upregulation of type iii endothelial cell nitric oxide synthase by agents that disrupt actin cytoskeletal organization |
AUPP891299A0 (en) | 1999-02-26 | 1999-03-25 | Fujisawa Pharmaceutical Co., Ltd. | New 6-membered cyclic compounds |
AUPQ309399A0 (en) | 1999-09-28 | 1999-10-21 | Fujisawa Pharmaceutical Co., Ltd. | Benzothiazoline derivatives |
TWI241190B (en) * | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
PE20020870A1 (es) * | 2001-02-13 | 2002-11-18 | Aventis Pharma Gmbh | 6,7,8,9-tetrahidro-5h-benzocicloheptenil aminas aciladas |
PE20020856A1 (es) * | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
TWI243164B (en) * | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
US7338956B2 (en) * | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
US7186735B2 (en) * | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
US7105513B2 (en) * | 2002-08-07 | 2006-09-12 | Sanofi-Avertis Deutschland Gmbh | Acylated, heteroaryl-condensed cycloalkenylamines and their use as pharmaceuticals |
US8309608B2 (en) * | 2003-11-06 | 2012-11-13 | Sanofi-Aventis Deutschland Gmbh | Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases |
-
2002
- 2002-02-11 PE PE2002000103A patent/PE20020870A1/es not_active Application Discontinuation
- 2002-02-11 AR ARP020100441A patent/AR035431A1/es active IP Right Grant
- 2002-02-11 MY MYPI20020476A patent/MY136316A/en unknown
- 2002-02-12 CN CNB028048563A patent/CN1296346C/zh not_active Expired - Fee Related
- 2002-02-12 JP JP2002564479A patent/JP4319836B2/ja not_active Expired - Fee Related
- 2002-02-12 CA CA002438324A patent/CA2438324C/en not_active Expired - Fee Related
- 2002-02-12 CZ CZ20032134A patent/CZ20032134A3/cs unknown
- 2002-02-12 SK SK1009-2003A patent/SK10092003A3/sk unknown
- 2002-02-12 EE EEP200300370A patent/EE200300370A/xx unknown
- 2002-02-12 PT PT02722069T patent/PT1362027E/pt unknown
- 2002-02-12 ES ES02722069T patent/ES2304432T3/es not_active Expired - Lifetime
- 2002-02-12 HU HU0303133A patent/HUP0303133A3/hu unknown
- 2002-02-12 RU RU2003127723/04A patent/RU2301797C2/ru not_active IP Right Cessation
- 2002-02-12 DE DE60226704T patent/DE60226704D1/de not_active Expired - Lifetime
- 2002-02-12 PL PL02363639A patent/PL363639A1/xx not_active Application Discontinuation
- 2002-02-12 AU AU2002253012A patent/AU2002253012B2/en not_active Ceased
- 2002-02-12 EP EP02722069A patent/EP1362027B1/en not_active Expired - Lifetime
- 2002-02-12 DK DK02722069T patent/DK1362027T3/da active
- 2002-02-12 NZ NZ527471A patent/NZ527471A/en unknown
- 2002-02-12 MX MXPA03006893A patent/MXPA03006893A/es active IP Right Grant
- 2002-02-12 IL IL15721102A patent/IL157211A0/xx unknown
- 2002-02-12 AT AT02722069T patent/ATE396171T1/de active
- 2002-02-12 YU YU64203A patent/YU64203A/sh unknown
- 2002-02-12 WO PCT/EP2002/001449 patent/WO2002064546A2/en active IP Right Grant
- 2002-02-12 BR BR0207197-5A patent/BR0207197A/pt not_active IP Right Cessation
- 2002-02-12 KR KR1020037010680A patent/KR100975781B1/ko not_active IP Right Cessation
- 2002-02-13 US US10/073,203 patent/US6759412B2/en not_active Expired - Lifetime
- 2002-02-13 UY UY27165A patent/UY27165A1/es unknown
-
2003
- 2003-07-14 ZA ZA200305414A patent/ZA200305414B/en unknown
- 2003-08-03 IL IL157211A patent/IL157211A/en not_active IP Right Cessation
- 2003-08-05 BG BG108060A patent/BG108060A/bg unknown
- 2003-08-12 NO NO20033566A patent/NO328767B1/no not_active IP Right Cessation
- 2003-08-12 HR HR20030645A patent/HRP20030645A2/hr not_active Application Discontinuation
-
2004
- 2004-05-03 HK HK04103983A patent/HK1061017A1/xx not_active IP Right Cessation
- 2004-06-03 US US10/859,773 patent/US7709478B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200305414B (en) | Acylated 6, 7, 8, 9-tetrahydro-5H-benzocycloheptenyl amines and their use as pharmaceutical. | |
US7713963B2 (en) | Acylated indanyl amines and their use as pharmaceuticals | |
CA2437950C (en) | Acylated 1,2,3,4-tetrahydronaphthyl amines and their use as pharmaceutical | |
AU2002253012A1 (en) | Acylated 6,7,8,9-tetrahydro-5H-benzocycloheptenyl amines and their use as pharmaceutical | |
AU2002250920A1 (en) | Acylated 1,2,3,4-tetrahydronaphthyl amines and their use as pharmaceutical | |
AU2002253010A1 (en) | Acylated indanyl amines and their use as pharmaceuticals | |
ZA200410273B (en) | Acylated arylcycloalkylamines and their use as pharmaceuticals |