KR20050043967A - 1-피리딘-4-일-요소 유도체 - Google Patents

Info

Publication number

KR20050043967A

KR20050043967A KR1020057004455A KR20057004455A KR20050043967A KR 20050043967 A KR20050043967 A KR 20050043967A KR 1020057004455 A KR1020057004455 A KR 1020057004455A KR 20057004455 A KR20057004455 A KR 20057004455A KR 20050043967 A KR20050043967 A KR 20050043967A

Authority

KR

South Korea

Prior art keywords

pyrrolidin

methyl

diphenyl

quinolin

urea

Prior art date

2002-09-17

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

Withdrawn

Links

• Espacenet
• Global Dossier
• Discuss

• ICJVRPQWEPOSOL-UHFFFAOYSA-N pyridin-4-ylurea Chemical class NC(=O)NC1=CC=NC=C1 ICJVRPQWEPOSOL-UHFFFAOYSA-N 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 169
• 238000000034 method Methods 0.000 claims abstract description 40
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 239000005557 antagonist Substances 0.000 claims abstract description 6
• -1 [1,8] naphthyridin-4-yl Chemical group 0.000 claims description 175
• 125000000217 alkyl group Chemical group 0.000 claims description 70
• 239000000203 mixture Substances 0.000 claims description 59
• 229910052757 nitrogen Inorganic materials 0.000 claims description 52
• 239000001257 hydrogen Substances 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 44
• 108010018369 Urotensin II Proteins 0.000 claims description 34
• 102000050488 Urotensin II Human genes 0.000 claims description 34
• 125000003118 aryl group Chemical group 0.000 claims description 34
• HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 claims description 33
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
• 125000006413 ring segment Chemical group 0.000 claims description 28
• 150000002431 hydrogen Chemical class 0.000 claims description 27
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
• 201000010099 disease Diseases 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
• 239000002904 solvent Chemical class 0.000 claims description 12
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
• 239000004202 carbamide Substances 0.000 claims description 10
• 150000003839 salts Chemical class 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 9
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 206010019280 Heart failures Diseases 0.000 claims description 7
• 239000000463 material Substances 0.000 claims description 7
• 102000005962 receptors Human genes 0.000 claims description 7
• 108020003175 receptors Proteins 0.000 claims description 7
• 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 claims description 6
• 206010037423 Pulmonary oedema Diseases 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 208000005333 pulmonary edema Diseases 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 206010012289 Dementia Diseases 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 210000003734 kidney Anatomy 0.000 claims description 5
• 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 5
• 230000002792 vascular Effects 0.000 claims description 5
• CQQYYZAJXUOHTN-QHCPKHFHSA-N 1-(2,6-dimethylpyridin-4-yl)-3-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]urea Chemical compound CC1=NC(C)=CC(NC(=O)N[C@@H]2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 CQQYYZAJXUOHTN-QHCPKHFHSA-N 0.000 claims description 4
• ALXDTSKWSQIQBV-VWLOTQADSA-N 1-[(3s)-1-(1,3-diphenylpropan-2-yl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C3C=CC=CC3=2)C)CN1C(CC=1C=CC=CC=1)CC1=CC=CC=C1 ALXDTSKWSQIQBV-VWLOTQADSA-N 0.000 claims description 4
• MKBMVELFWQNGRT-HKBQPEDESA-N 1-[(3s)-1-(3,3-diphenylpropyl)pyrrolidin-3-yl]-3-[2-methyl-6-(2-phenylethyl)pyridin-4-yl]urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C(CCC=3C=CC=CC=3)C=2)C)CN1CCC(C=1C=CC=CC=1)C1=CC=CC=C1 MKBMVELFWQNGRT-HKBQPEDESA-N 0.000 claims description 4
• 206010016654 Fibrosis Diseases 0.000 claims description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 238000002399 angioplasty Methods 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 230000007882 cirrhosis Effects 0.000 claims description 4
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
• 210000000056 organ Anatomy 0.000 claims description 4
• 208000007232 portal hypertension Diseases 0.000 claims description 4
• 238000002054 transplantation Methods 0.000 claims description 4
• AVXTWBHRXGTMNK-DEOSSOPVSA-N 1-(2,6-dimethylpyridin-4-yl)-3-[(3s)-1-(1,3-diphenylpropan-2-yl)pyrrolidin-3-yl]urea Chemical compound CC1=NC(C)=CC(NC(=O)N[C@@H]2CN(CC2)C(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 AVXTWBHRXGTMNK-DEOSSOPVSA-N 0.000 claims description 3
• VASZNWWWMQOFBM-VWLOTQADSA-N 1-[(3s)-1-(1,3-diphenylpropan-2-yl)pyrrolidin-3-yl]-3-(2-ethyl-6-methylpyridin-4-yl)urea Chemical compound CC1=NC(CC)=CC(NC(=O)N[C@@H]2CN(CC2)C(CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 VASZNWWWMQOFBM-VWLOTQADSA-N 0.000 claims description 3
• CYWRXQDEQUAXFP-DEOSSOPVSA-N 1-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]-3-(2-ethyl-6-methylpyridin-4-yl)urea Chemical compound CC1=NC(CC)=CC(NC(=O)N[C@@H]2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 CYWRXQDEQUAXFP-DEOSSOPVSA-N 0.000 claims description 3
• HVEANDTZNLHJIQ-QFIPXVFZSA-N 1-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]-3-[2-(methylamino)pyridin-4-yl]urea Chemical compound C1=NC(NC)=CC(NC(=O)N[C@@H]2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 HVEANDTZNLHJIQ-QFIPXVFZSA-N 0.000 claims description 3
• VUTISFXPLPGWAS-PMERELPUSA-N 1-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]-3-[2-methyl-6-(2-phenylethyl)pyridin-4-yl]urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C(CCC=3C=CC=CC=3)C=2)C)CN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 VUTISFXPLPGWAS-PMERELPUSA-N 0.000 claims description 3
• RSDWXTZHJWMBLA-NDEPHWFRSA-N 1-[2-(benzylamino)pyridin-4-yl]-3-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(NCC=3C=CC=CC=3)N=CC=2)CN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 RSDWXTZHJWMBLA-NDEPHWFRSA-N 0.000 claims description 3
• CJEDMDDAFSHOSR-SANMLTNESA-N 1-[2-(cyclopentylamino)pyridin-4-yl]-3-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(NC3CCCC3)N=CC=2)CN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 CJEDMDDAFSHOSR-SANMLTNESA-N 0.000 claims description 3
• GKIPRRXILIPLFF-LJAQVGFWSA-N 1-[2-[benzyl(methyl)amino]pyridin-4-yl]-3-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]urea Chemical compound C=1C(NC(=O)N[C@@H]2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=CC=NC=1N(C)CC1=CC=CC=C1 GKIPRRXILIPLFF-LJAQVGFWSA-N 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 206010002383 Angina Pectoris Diseases 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
• 201000006474 Brain Ischemia Diseases 0.000 claims description 3
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
• 206010059109 Cerebral vasoconstriction Diseases 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 206010010904 Convulsion Diseases 0.000 claims description 3
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 3
• 108010036949 Cyclosporine Proteins 0.000 claims description 3
• 206010011878 Deafness Diseases 0.000 claims description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
• 208000010412 Glaucoma Diseases 0.000 claims description 3
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
• 208000019695 Migraine disease Diseases 0.000 claims description 3
• 208000002193 Pain Diseases 0.000 claims description 3
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
• 208000012322 Raynaud phenomenon Diseases 0.000 claims description 3
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
• 206010038490 Renal pain Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 206010003119 arrhythmia Diseases 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 206010008118 cerebral infarction Diseases 0.000 claims description 3
• 208000007451 chronic bronchitis Diseases 0.000 claims description 3
• 208000020832 chronic kidney disease Diseases 0.000 claims description 3
• 229960001265 ciclosporin Drugs 0.000 claims description 3
• 208000018631 connective tissue disease Diseases 0.000 claims description 3
• 229930182912 cyclosporin Natural products 0.000 claims description 3
• 206010013663 drug dependence Diseases 0.000 claims description 3
• 230000010370 hearing loss Effects 0.000 claims description 3
• 231100000888 hearing loss Toxicity 0.000 claims description 3
• 208000016354 hearing loss disease Diseases 0.000 claims description 3
• 201000001881 impotence Diseases 0.000 claims description 3
• 208000001286 intracranial vasospasm Diseases 0.000 claims description 3
• 208000028867 ischemia Diseases 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 206010027599 migraine Diseases 0.000 claims description 3
• 230000000877 morphologic effect Effects 0.000 claims description 3
• 208000031225 myocardial ischemia Diseases 0.000 claims description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 201000000980 schizophrenia Diseases 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 208000011117 substance-related disease Diseases 0.000 claims description 3
• 208000024891 symptom Diseases 0.000 claims description 3
• 230000006016 thyroid dysfunction Effects 0.000 claims description 3
• 229920002554 vinyl polymer Polymers 0.000 claims description 3
• 208000002177 Cataract Diseases 0.000 claims description 2
• 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 2
• 125000004104 aryloxy group Chemical group 0.000 claims description 2
• 239000002876 beta blocker Substances 0.000 claims description 2
• 238000007675 cardiac surgery Methods 0.000 claims description 2
• 239000002308 endothelin receptor antagonist Substances 0.000 claims description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
• 208000018360 neuromuscular disease Diseases 0.000 claims description 2
• 238000007631 vascular surgery Methods 0.000 claims description 2
• 208000002249 Diabetes Complications Diseases 0.000 claims 2
• 206010012655 Diabetic complications Diseases 0.000 claims 2
• 229940116211 Vasopressin antagonist Drugs 0.000 claims 2
• 239000002671 adjuvant Substances 0.000 claims 2
• 239000012050 conventional carrier Substances 0.000 claims 2
• 239000003038 vasopressin antagonist Substances 0.000 claims 2
• XUHRVZXFBWDCFB-QRTDKPMLSA-N (3R)-4-[[(3S,6S,9S,12R,15S,18R,21R,24R,27R,28R)-12-(3-amino-3-oxopropyl)-6-[(2S)-butan-2-yl]-3-(2-carboxyethyl)-18-(hydroxymethyl)-28-methyl-9,15,21,24-tetrakis(2-methylpropyl)-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-27-yl]amino]-3-[[(2R)-2-[[(3S)-3-hydroxydecanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid Chemical compound CCCCCCC[C@H](O)CC(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H]1[C@@H](C)OC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CO)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC1=O)[C@@H](C)CC XUHRVZXFBWDCFB-QRTDKPMLSA-N 0.000 claims 1
• 239000005541 ACE inhibitor Substances 0.000 claims 1
• 102100024547 Tensin-1 Human genes 0.000 claims 1
• 108010088950 Tensins Proteins 0.000 claims 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 1
• 239000000674 adrenergic antagonist Substances 0.000 claims 1
• 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
• 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
• 230000004064 dysfunction Effects 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 201000001441 melanoma Diseases 0.000 claims 1
• 230000002107 myocardial effect Effects 0.000 claims 1
• 238000001356 surgical procedure Methods 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 15
• 239000000712 neurohormone Substances 0.000 abstract description 4
• 230000008569 process Effects 0.000 abstract description 3
• 239000004480 active ingredient Substances 0.000 abstract description 2
• 102000008434 neuropeptide hormone activity proteins Human genes 0.000 abstract description 2
• 108040002669 neuropeptide hormone activity proteins Proteins 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
• 239000000243 solution Substances 0.000 description 26
• 239000011734 sodium Substances 0.000 description 25
• 239000000284 extract Substances 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
• 239000000725 suspension Substances 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 229910004298 SiO 2 Inorganic materials 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 108050002984 Urotensin II receptors Proteins 0.000 description 9
• 102000012327 Urotensin II receptors Human genes 0.000 description 9
• 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 description 8
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 239000002464 receptor antagonist Substances 0.000 description 8
• 229940044551 receptor antagonist Drugs 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• FVEMTYLFDDYDNA-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-pyrrolidin-3-ylurea;dihydrochloride Chemical compound Cl.Cl.C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1CCNC1 FVEMTYLFDDYDNA-UHFFFAOYSA-N 0.000 description 6
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 6
• 230000027455 binding Effects 0.000 description 6
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 238000010791 quenching Methods 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 6
• 150000003928 4-aminopyridines Chemical class 0.000 description 5
• 101000841325 Homo sapiens Urotensin-2 Proteins 0.000 description 5
• 229910010082 LiAlH Inorganic materials 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• BDQDKBPLBHUDPT-KRWDZBQOSA-N (3s)-1-(2,2-diphenylethyl)pyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 BDQDKBPLBHUDPT-KRWDZBQOSA-N 0.000 description 4
• LZZUZEUKHIXPFM-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-[(3-phenylphenyl)methyl]pyrrolidin-3-yl]urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CC(C=1)=CC=CC=1C1=CC=CC=C1 LZZUZEUKHIXPFM-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 238000012512 characterization method Methods 0.000 description 4
• 235000019439 ethyl acetate Nutrition 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 238000011065 in-situ storage Methods 0.000 description 4
• 230000001965 increasing effect Effects 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 239000012948 isocyanate Substances 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 229920005862 polyol Polymers 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• TZKSIKMEPYRPTG-SFHVURJKSA-N (3s)-1-(3,3-diphenylpropyl)pyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1CCC(C=1C=CC=CC=1)C1=CC=CC=C1 TZKSIKMEPYRPTG-SFHVURJKSA-N 0.000 description 3
• HFNHAPQMXICKCF-FDMLFMOBSA-N (4s)-4-amino-5-[[(2s,3r)-1-[(2r)-2-[[(2s)-1-[[(4r,7s,10r,13s,16r,19s)-10-(4-aminobutyl)-16-benzyl-4-[[(1s)-1-carboxy-2-methylpropyl]carbamoyl]-7-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloi Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-FDMLFMOBSA-N 0.000 description 3
• YFKBXYGUSOXJGS-UHFFFAOYSA-N 1,3-Diphenyl-2-propanone Chemical compound C=1C=CC=CC=1CC(=O)CC1=CC=CC=C1 YFKBXYGUSOXJGS-UHFFFAOYSA-N 0.000 description 3
• VMIZAIMXAFAAJC-QHCPKHFHSA-N 1-(2-methylquinolin-4-yl)-3-[(3s)-1-[(2-phenylphenyl)methyl]pyrrolidin-3-yl]urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C3C=CC=CC3=2)C)CN1CC1=CC=CC=C1C1=CC=CC=C1 VMIZAIMXAFAAJC-QHCPKHFHSA-N 0.000 description 3
• YAMBRNOLFOVLAX-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-pyrrolidin-3-ylurea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1CCNC1 YAMBRNOLFOVLAX-UHFFFAOYSA-N 0.000 description 3
• ALXDTSKWSQIQBV-UHFFFAOYSA-N 1-[1-(1,3-diphenylpropan-2-yl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1C(CC=1C=CC=CC=1)CC1=CC=CC=C1 ALXDTSKWSQIQBV-UHFFFAOYSA-N 0.000 description 3
• CRTFHNZNUSVPFV-UHFFFAOYSA-N 1-[1-(2,2-diphenylethyl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 CRTFHNZNUSVPFV-UHFFFAOYSA-N 0.000 description 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• SQSYNRCXIZHKAI-UHFFFAOYSA-N 2,6-dichloroisonicotinic acid Chemical compound OC(=O)C1=CC(Cl)=NC(Cl)=C1 SQSYNRCXIZHKAI-UHFFFAOYSA-N 0.000 description 3
• ZJXMKPARTVOUAM-UHFFFAOYSA-N 2,6-dimethylpyridin-4-amine Chemical compound CC1=CC(N)=CC(C)=N1 ZJXMKPARTVOUAM-UHFFFAOYSA-N 0.000 description 3
• ZGZMEKHQIZSZOH-UHFFFAOYSA-N 2-chloro-6-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(Cl)=N1 ZGZMEKHQIZSZOH-UHFFFAOYSA-N 0.000 description 3
• CQMGLAOQDAJDSS-UHFFFAOYSA-N 2-methyl-6-(2-phenylethyl)pyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(CCC=2C=CC=CC=2)=N1 CQMGLAOQDAJDSS-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 241000251468 Actinopterygii Species 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 102000026557 Urotensins Human genes 0.000 description 3
• 108010011107 Urotensins Proteins 0.000 description 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 230000003197 catalytic effect Effects 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
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 102000047478 human UTS2 Human genes 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• AQBLLJNPHDIAPN-LNTINUHCSA-K iron(3+);(z)-4-oxopent-2-en-2-olate Chemical compound [Fe+3].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O AQBLLJNPHDIAPN-LNTINUHCSA-K 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
• 150000003077 polyols Chemical class 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 230000008707 rearrangement Effects 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 238000007614 solvation Methods 0.000 description 3
• WZWKODYUZDFLPG-UHFFFAOYSA-N tert-butyl 2-chloro-6-methylpyridine-4-carboxylate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC(Cl)=N1 WZWKODYUZDFLPG-UHFFFAOYSA-N 0.000 description 3
• AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 3
• DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 3
• 239000000780 urotensin Substances 0.000 description 3
• 239000005526 vasoconstrictor agent Substances 0.000 description 3
• IVTXBEQPEKFFPI-SFHVURJKSA-N (3s)-1-(1,3-diphenylpropan-2-yl)pyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1C(CC=1C=CC=CC=1)CC1=CC=CC=C1 IVTXBEQPEKFFPI-SFHVURJKSA-N 0.000 description 2
• GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical compound C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-N 0.000 description 2
• CSJXSJKKACKVQN-UHFFFAOYSA-N 1-(1-benzylpyrrolidin-3-yl)-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CC1=CC=CC=C1 CSJXSJKKACKVQN-UHFFFAOYSA-N 0.000 description 2
• DPDDVTVONRJHBM-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-(1-phenylethyl)pyrrolidin-3-yl]urea Chemical compound C1CC(NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)CN1C(C)C1=CC=CC=C1 DPDDVTVONRJHBM-UHFFFAOYSA-N 0.000 description 2
• OBNSKGHLBBYGFD-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-(3-phenylpropyl)pyrrolidin-3-yl]urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CCCC1=CC=CC=C1 OBNSKGHLBBYGFD-UHFFFAOYSA-N 0.000 description 2
• NSSFGHRLJFJRDV-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-(naphthalen-1-ylmethyl)pyrrolidin-3-yl]urea Chemical compound C1=CC=CC2=NC(C)=CC(NC(=O)NC3CN(CC=4C5=CC=CC=C5C=CC=4)CC3)=C21 NSSFGHRLJFJRDV-UHFFFAOYSA-N 0.000 description 2
• XISUXQPUSTXGNA-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-(naphthalen-2-ylmethyl)pyrrolidin-3-yl]urea Chemical compound C1=CC=CC2=NC(C)=CC(NC(=O)NC3CN(CC=4C=C5C=CC=CC5=CC=4)CC3)=C21 XISUXQPUSTXGNA-UHFFFAOYSA-N 0.000 description 2
• NQNGYSXJFKNLEU-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-[1-[(4-phenylphenyl)methyl]pyrrolidin-3-yl]urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 NQNGYSXJFKNLEU-UHFFFAOYSA-N 0.000 description 2
• HQKNRZGCWMSVKG-TUXUZCGSSA-N 1-[(3s)-1-(1,1-diphenylpropan-2-yl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C([C@H](CC1)NC(=O)NC=2C3=CC=CC=C3N=C(C)C=2)N1C(C)C(C=1C=CC=CC=1)C1=CC=CC=C1 HQKNRZGCWMSVKG-TUXUZCGSSA-N 0.000 description 2
• IMDOYOHUOKYNCY-DEOSSOPVSA-N 1-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]-3-[2-(propylamino)pyridin-4-yl]urea Chemical compound C1=NC(NCCC)=CC(NC(=O)N[C@@H]2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 IMDOYOHUOKYNCY-DEOSSOPVSA-N 0.000 description 2
• SIEDSGWYFKYBTE-DEOSSOPVSA-N 1-[(3s)-1-(2-hydroxy-2,2-diphenylethyl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C3C=CC=CC3=2)C)CN1CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 SIEDSGWYFKYBTE-DEOSSOPVSA-N 0.000 description 2
• CSJXSJKKACKVQN-SFHVURJKSA-N 1-[(3s)-1-benzylpyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C([C@@H](C1)NC(=O)NC=2C=C(N=C3C=CC=CC3=2)C)CN1CC1=CC=CC=C1 CSJXSJKKACKVQN-SFHVURJKSA-N 0.000 description 2
• DHHPOFYXYGSYAA-UHFFFAOYSA-N 1-[1-(2,2-diphenylethyl)piperidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 DHHPOFYXYGSYAA-UHFFFAOYSA-N 0.000 description 2
• SIEDSGWYFKYBTE-UHFFFAOYSA-N 1-[1-(2-hydroxy-2,2-diphenylethyl)pyrrolidin-3-yl]-3-(2-methylquinolin-4-yl)urea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC(C1)CCN1CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 SIEDSGWYFKYBTE-UHFFFAOYSA-N 0.000 description 2
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
• XVCGTFIEKHXNQA-SANMLTNESA-N 1-[[(2s)-1-(1,3-diphenylpropan-2-yl)pyrrolidin-2-yl]methyl]-3-(2-methylquinolin-4-yl)urea Chemical compound C([C@H]1CNC(=O)NC=2C=C(N=C3C=CC=CC3=2)C)CCN1C(CC=1C=CC=CC=1)CC1=CC=CC=C1 XVCGTFIEKHXNQA-SANMLTNESA-N 0.000 description 2
• HLLGFGBLKOIZOM-UHFFFAOYSA-N 2,2-diphenylacetaldehyde Chemical compound C=1C=CC=CC=1C(C=O)C1=CC=CC=C1 HLLGFGBLKOIZOM-UHFFFAOYSA-N 0.000 description 2
• LFPUGENPUAERSG-UHFFFAOYSA-N 2,6-dimethyl-4-nitro-1-oxidopyridin-1-ium Chemical compound CC1=CC([N+]([O-])=O)=CC(C)=[N+]1[O-] LFPUGENPUAERSG-UHFFFAOYSA-N 0.000 description 2
• CCTUAAXUBUEECR-UHFFFAOYSA-N 2-chloro-6-(propylamino)pyridine-4-carboxylic acid Chemical compound CCCNC1=CC(C(O)=O)=CC(Cl)=N1 CCTUAAXUBUEECR-UHFFFAOYSA-N 0.000 description 2
• GZCVYOBQSSOCBS-UHFFFAOYSA-N 2-ethyl-4-isocyanato-6-methylpyridine Chemical compound CCC1=CC(N=C=O)=CC(C)=N1 GZCVYOBQSSOCBS-UHFFFAOYSA-N 0.000 description 2
• SLXNIYNYZLVIOM-UHFFFAOYSA-N 2-methyl-6-(2-phenylethenyl)pyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(C=CC=2C=CC=CC=2)=N1 SLXNIYNYZLVIOM-UHFFFAOYSA-N 0.000 description 2
• COCFIBRMFPWUDW-UHFFFAOYSA-N 2-methylquinolin-4-amine Chemical compound C1=CC=CC2=NC(C)=CC(N)=C21 COCFIBRMFPWUDW-UHFFFAOYSA-N 0.000 description 2
• BZQGAPWJKAYCHR-UHFFFAOYSA-N 3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(CC(=O)O)C1=CC=CC=C1 BZQGAPWJKAYCHR-UHFFFAOYSA-N 0.000 description 2
• GJVLGFXSSHQNGT-UHFFFAOYSA-N 4-bromo-2,2-diphenylbutanoyl chloride Chemical compound C=1C=CC=CC=1C(CCBr)(C(=O)Cl)C1=CC=CC=C1 GJVLGFXSSHQNGT-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• SGGYDYGRESJMHW-UHFFFAOYSA-N 4-isocyanato-2-methyl-6-(2-phenylethenyl)pyridine Chemical compound CC1=CC(N=C=O)=CC(C=CC=2C=CC=CC=2)=N1 SGGYDYGRESJMHW-UHFFFAOYSA-N 0.000 description 2
• AOEHQUMYCBIKLQ-UHFFFAOYSA-N 4-isocyanato-2-methyl-6-(2-phenylethyl)pyridine Chemical compound CC1=CC(N=C=O)=CC(CCC=2C=CC=CC=2)=N1 AOEHQUMYCBIKLQ-UHFFFAOYSA-N 0.000 description 2
• FMMMIORVRIDESI-UHFFFAOYSA-N 6-chloro-4-isocyanato-n-propylpyridin-2-amine Chemical compound CCCNC1=CC(N=C=O)=CC(Cl)=N1 FMMMIORVRIDESI-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 101000932768 Conus catus Alpha-conotoxin CIC Proteins 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 102000016978 Orphan receptors Human genes 0.000 description 2
• 108070000031 Orphan receptors Proteins 0.000 description 2
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
• 241000009328 Perro Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 101710205907 Urotensin-2 receptor Proteins 0.000 description 2
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 208000020990 adrenal cortex carcinoma Diseases 0.000 description 2
• 239000003513 alkali Substances 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 239000012491 analyte Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• 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 2
• 239000004305 biphenyl Chemical group 0.000 description 2
• QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
• 210000004413 cardiac myocyte Anatomy 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 230000008602 contraction Effects 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 230000008482 dysregulation Effects 0.000 description 2
• 239000006274 endogenous ligand Substances 0.000 description 2
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 150000002367 halogens Chemical class 0.000 description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 230000001969 hypertrophic effect Effects 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• BDCOESSGNHGZTD-UHFFFAOYSA-N n-benzyl-4-isocyanato-n-methylpyridin-2-amine Chemical compound C=1C(N=C=O)=CC=NC=1N(C)CC1=CC=CC=C1 BDCOESSGNHGZTD-UHFFFAOYSA-N 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
• 230000001012 protector Effects 0.000 description 2
• 239000002516 radical scavenger Substances 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
• NIORFBKWKQYCLC-UHFFFAOYSA-N tert-butyl 3-[(2-methylquinolin-4-yl)carbamoylamino]pyrrolidine-1-carboxylate Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1CCN(C(=O)OC(C)(C)C)C1 NIORFBKWKQYCLC-UHFFFAOYSA-N 0.000 description 2
• CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 2
• ZJZMMQUSARWGKE-FQEVSTJZSA-N tert-butyl n-[(3s)-1-(2,2-diphenylethyl)pyrrolidin-3-yl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC(C=1C=CC=CC=1)C1=CC=CC=C1 ZJZMMQUSARWGKE-FQEVSTJZSA-N 0.000 description 2
• GIAROZXEUXOFDV-FQEVSTJZSA-N tert-butyl n-[(3s)-1-(3,3-diphenylpropanoyl)pyrrolidin-3-yl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 GIAROZXEUXOFDV-FQEVSTJZSA-N 0.000 description 2
• OWKWDDLUYYPAFG-NRFANRHFSA-N tert-butyl n-[(3s)-1-(3,3-diphenylpropyl)pyrrolidin-3-yl]carbamate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCN1CCC(C=1C=CC=CC=1)C1=CC=CC=C1 OWKWDDLUYYPAFG-NRFANRHFSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 210000001042 thoracic artery Anatomy 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 150000003672 ureas Chemical class 0.000 description 2
• 230000002227 vasoactive effect Effects 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
• VLJNHYLEOZPXFW-SCSAIBSYSA-N (2r)-pyrrolidine-2-carboxamide Chemical compound NC(=O)[C@H]1CCCN1 VLJNHYLEOZPXFW-SCSAIBSYSA-N 0.000 description 1
• YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• JOBSULVKGHFPLU-UHFFFAOYSA-N 1,3-bis(2,6-dimethylpyridin-4-yl)urea Chemical compound CC1=NC(C)=CC(NC(=O)NC=2C=C(C)N=C(C)C=2)=C1 JOBSULVKGHFPLU-UHFFFAOYSA-N 0.000 description 1
• VBSSTIRZSHPIIX-UHFFFAOYSA-N 1-(2-methylquinolin-4-yl)-3-piperidin-3-ylurea Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=O)NC1CCCNC1 VBSSTIRZSHPIIX-UHFFFAOYSA-N 0.000 description 1
• RTFPTPXBTIUISM-UHFFFAOYSA-N 1-(bromomethyl)-3-phenylbenzene Chemical compound BrCC1=CC=CC(C=2C=CC=CC=2)=C1 RTFPTPXBTIUISM-UHFFFAOYSA-N 0.000 description 1
• DBMMTKKCTNZCIH-VWLOTQADSA-N 1-[(3s)-1-(3,3-diphenylpropyl)pyrrolidin-3-yl]-3-(2-ethyl-6-methylpyridin-4-yl)urea Chemical compound CC1=NC(CC)=CC(NC(=O)N[C@@H]2CN(CCC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 DBMMTKKCTNZCIH-VWLOTQADSA-N 0.000 description 1
• DVSNNCDHBUEMEW-UHFFFAOYSA-N 1-[2-chloro-6-(propylamino)pyridin-4-yl]-3-[1-(2,2-diphenylethyl)pyrrolidin-3-yl]urea Chemical compound ClC1=NC(NCCC)=CC(NC(=O)NC2CN(CC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)=C1 DVSNNCDHBUEMEW-UHFFFAOYSA-N 0.000 description 1
• HBVNLKQGRZPGRP-UHFFFAOYSA-N 1-benzylpyrrolidin-3-amine Chemical compound C1C(N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-UHFFFAOYSA-N 0.000 description 1
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• GNTBNWVFOVGGBY-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[2,3-b]quinolin-4-amine Chemical class C1=CC=C2C(N)=C(CCN3)C3=NC2=C1 GNTBNWVFOVGGBY-UHFFFAOYSA-N 0.000 description 1
• LIDGFHXPUOJZMK-UHFFFAOYSA-N 2,6-dimethyl-1-oxidopyridin-1-ium Chemical compound CC1=CC=CC(C)=[N+]1[O-] LIDGFHXPUOJZMK-UHFFFAOYSA-N 0.000 description 1
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 1
• YNJLIJYZNAIILE-KRWDZBQOSA-N 2-[(3s)-3-aminopyrrolidin-1-yl]-1,1-diphenylethanol Chemical compound C1[C@@H](N)CCN1CC(O)(C=1C=CC=CC=1)C1=CC=CC=C1 YNJLIJYZNAIILE-KRWDZBQOSA-N 0.000 description 1
• CXXPGKUGENRIFR-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)ethenyl]-4-isocyanato-6-methylpyridine Chemical compound CC1=CC(N=C=O)=CC(C=CC=2C=CC(F)=CC=2)=N1 CXXPGKUGENRIFR-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• VRSQKAXGYDIOFP-UHFFFAOYSA-N 2-[benzyl(methyl)amino]pyridine-4-carboxylic acid Chemical compound C=1C(C(O)=O)=CC=NC=1N(C)CC1=CC=CC=C1 VRSQKAXGYDIOFP-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• QXCOHSRHFCHCHN-UHFFFAOYSA-N 2-chloropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=C1 QXCOHSRHFCHCHN-UHFFFAOYSA-N 0.000 description 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical class NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
• DIMZSHAYNGNBSP-UHFFFAOYSA-N 4-isocyanato-2-methyl-6-propylpyridine Chemical compound CCCC1=CC(N=C=O)=CC(C)=N1 DIMZSHAYNGNBSP-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• WGSMWYVILOTLIH-UHFFFAOYSA-N 6-chloro-n-cyclopentyl-4-isocyanatopyridin-2-amine Chemical compound ClC1=CC(N=C=O)=CC(NC2CCCC2)=N1 WGSMWYVILOTLIH-UHFFFAOYSA-N 0.000 description 1
• 102400000345 Angiotensin-2 Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 208000006386 Bone Resorption Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
• 102000004499 CCR3 Receptors Human genes 0.000 description 1
• 108010017316 CCR3 Receptors Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229940127291 Calcium channel antagonist Drugs 0.000 description 1
• GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-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
• 108010061435 Enalapril Proteins 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• 102400000686 Endothelin-1 Human genes 0.000 description 1
• 101800004490 Endothelin-1 Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• WDZVGELJXXEGPV-YIXHJXPBSA-N Guanabenz Chemical compound NC(N)=N\N=C\C1=C(Cl)C=CC=C1Cl WDZVGELJXXEGPV-YIXHJXPBSA-N 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 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
• 241000282567 Macaca fascicularis Species 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 229940083963 Peptide antagonist Drugs 0.000 description 1
• QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102000004257 Potassium Channel Human genes 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• KXEMQEGRZWUKJS-UHFFFAOYSA-N Raufloridine Natural products COC1=CC=C2C(CCN3CC4C(C)OC=C(C4CC33)C(=O)OC)=C3NC2=C1 KXEMQEGRZWUKJS-UHFFFAOYSA-N 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-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
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 101150056450 UTS2R gene Proteins 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 239000002160 alpha blocker Substances 0.000 description 1
• 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
• 239000003524 antilipemic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 210000002376 aorta thoracic Anatomy 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 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
• 230000024279 bone resorption Effects 0.000 description 1
• GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
• 229960003065 bosentan Drugs 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
• 229960004064 bumetanide Drugs 0.000 description 1
• DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
• 239000003990 capacitor Substances 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 210000001054 cardiac fibroblast Anatomy 0.000 description 1
• 229940124461 cardiostimulant Drugs 0.000 description 1
• 229960001222 carteolol Drugs 0.000 description 1
• LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
• 229960005110 cerivastatin Drugs 0.000 description 1
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 229960002155 chlorothiazide Drugs 0.000 description 1
• JIVPVXMEBJLZRO-UHFFFAOYSA-N chlorthalidone Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-UHFFFAOYSA-N 0.000 description 1
• 229960002896 clonidine Drugs 0.000 description 1
• 229910052681 coesite Inorganic materials 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 229910052906 cristobalite Inorganic materials 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 210000000448 cultured tumor cell Anatomy 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 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
• SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 1
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 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
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 229960004042 diazoxide Drugs 0.000 description 1
• AGCOMFFHXJMNLN-UHFFFAOYSA-N dichloromethane;dihydrochloride Chemical compound Cl.Cl.ClCCl AGCOMFFHXJMNLN-UHFFFAOYSA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 235000013681 dietary sucrose Nutrition 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 229960004166 diltiazem Drugs 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• NLHWCTNYFFIPJT-UHFFFAOYSA-N disodium bis(trimethylsilyl)azanide Chemical compound [Na+].[Na+].C[Si](C)(C)[N-][Si](C)(C)C.C[Si](C)(C)[N-][Si](C)(C)C NLHWCTNYFFIPJT-UHFFFAOYSA-N 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229960001484 edetic acid Drugs 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
• 229960000873 enalapril Drugs 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 229960004563 eprosartan Drugs 0.000 description 1
• OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
• OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
• 235000019441 ethanol Nutrition 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000003176 fibrotic effect Effects 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 229960001606 flosequinan Drugs 0.000 description 1
• UYGONJYYUKVHDD-UHFFFAOYSA-N flosequinan Chemical compound C1=C(F)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 UYGONJYYUKVHDD-UHFFFAOYSA-N 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 229960003883 furosemide Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229960004553 guanabenz Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 210000002064 heart cell Anatomy 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 229960002474 hydralazine Drugs 0.000 description 1
• 229960002003 hydrochlorothiazide Drugs 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 239000008011 inorganic excipient Substances 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-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
• 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
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 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
• 229910052749 magnesium Inorganic materials 0.000 description 1
• DHZDXXLCWXHNOB-UHFFFAOYSA-M magnesium;ethylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]CC1=CC=CC=C1 DHZDXXLCWXHNOB-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 241001515942 marmosets Species 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
• 229960002817 metolazone Drugs 0.000 description 1
• 229960002237 metoprolol Drugs 0.000 description 1
• IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 229960003632 minoxidil Drugs 0.000 description 1
• DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• KDHIICUWNOIWAE-UHFFFAOYSA-N n-benzyl-6-chloro-4-isocyanatopyridin-2-amine Chemical compound ClC1=CC(N=C=O)=CC(NCC=2C=CC=CC=2)=N1 KDHIICUWNOIWAE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000003136 n-heptyl 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])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 230000000720 neurosecretory effect Effects 0.000 description 1
• 210000000607 neurosecretory system Anatomy 0.000 description 1
• 229960001783 nicardipine Drugs 0.000 description 1
• HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
• 229960001597 nifedipine Drugs 0.000 description 1
• 229960000715 nimodipine Drugs 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 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
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000008012 organic excipient Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 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
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229960003418 phenoxybenzamine Drugs 0.000 description 1
• MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
• 229960001999 phentolamine Drugs 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 108020001213 potassium channel Proteins 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 229960003712 propranolol Drugs 0.000 description 1
• 201000004240 prostatic hypertrophy Diseases 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• MQDVUDAZJMZQMF-UHFFFAOYSA-N pyridin-2-ylurea Chemical class NC(=O)NC1=CC=CC=N1 MQDVUDAZJMZQMF-UHFFFAOYSA-N 0.000 description 1
• IVBGRHGOAGXMBR-UHFFFAOYSA-N quinolin-2-ylurea Chemical class C1=CC=CC2=NC(NC(=O)N)=CC=C21 IVBGRHGOAGXMBR-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 201000010174 renal carcinoma Diseases 0.000 description 1
• QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
• MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 229960002855 simvastatin Drugs 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
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 229910052682 stishovite Inorganic materials 0.000 description 1
• 125000005504 styryl group Chemical group 0.000 description 1
• 239000003890 substance P antagonist Substances 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002889 sympathetic effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960000651 tasosartan Drugs 0.000 description 1
• ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
• 229960005187 telmisartan Drugs 0.000 description 1
• DJORFRMYLDPISV-UHFFFAOYSA-N tert-butyl 2-methyl-6-(2-phenylethyl)pyridine-4-carboxylate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC(CCC=2C=CC=CC=2)=N1 DJORFRMYLDPISV-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 229960004605 timolol Drugs 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
• 229910052905 tridymite Inorganic materials 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 1
• SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1