JP2017527604A - ｓＧＣ刺激剤 - Google Patents
ｓＧＣ刺激剤 Download PDFInfo
- Publication number
- JP2017527604A JP2017527604A JP2017515197A JP2017515197A JP2017527604A JP 2017527604 A JP2017527604 A JP 2017527604A JP 2017515197 A JP2017515197 A JP 2017515197A JP 2017515197 A JP2017515197 A JP 2017515197A JP 2017527604 A JP2017527604 A JP 2017527604A
- Authority
- JP
- Japan
- Prior art keywords
- ring
- alkyl
- membered heteroaryl
- membered heterocyclic
- membered
- Prior art date
- 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- Withdrawn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
- 150000001875 compounds Chemical class 0.000 claims abstract description 152
- 150000003839 salts Chemical class 0.000 claims abstract description 106
- 125000000217 alkyl group Chemical group 0.000 claims description 808
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 380
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 282
- 125000005842 heteroatom Chemical group 0.000 claims description 235
- 229910052717 sulfur Inorganic materials 0.000 claims description 235
- 229910052760 oxygen Inorganic materials 0.000 claims description 231
- 125000001931 aliphatic group Chemical group 0.000 claims description 228
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 220
- 229910052736 halogen Inorganic materials 0.000 claims description 195
- 150000002367 halogens Chemical group 0.000 claims description 188
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 179
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 177
- 229910052739 hydrogen Inorganic materials 0.000 claims description 173
- 239000001257 hydrogen Substances 0.000 claims description 173
- 229910052757 nitrogen Inorganic materials 0.000 claims description 165
- 125000004043 oxo group Chemical group O=* 0.000 claims description 163
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 154
- 125000000623 heterocyclic group Chemical group 0.000 claims description 125
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 115
- 229910052799 carbon Inorganic materials 0.000 claims description 99
- 125000002619 bicyclic group Chemical group 0.000 claims description 98
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 94
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 92
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 84
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 79
- 201000010099 disease Diseases 0.000 claims description 77
- 208000035475 disorder Diseases 0.000 claims description 74
- 125000001072 heteroaryl group Chemical group 0.000 claims description 66
- -1 3,3,3,2,2-pentafluoropropyl Chemical group 0.000 claims description 65
- 125000004429 atom Chemical group 0.000 claims description 65
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 58
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 125000002950 monocyclic group Chemical group 0.000 claims description 47
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 45
- 125000001153 fluoro group Chemical group F* 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 35
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 206010016654 Fibrosis Diseases 0.000 claims description 27
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 23
- 230000004761 fibrosis Effects 0.000 claims description 23
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 22
- 125000003003 spiro group Chemical group 0.000 claims description 21
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 20
- 230000002685 pulmonary effect Effects 0.000 claims description 19
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 17
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 17
- 208000017169 kidney disease Diseases 0.000 claims description 17
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 16
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 16
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 16
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 235000019000 fluorine Nutrition 0.000 claims description 14
- 230000001965 increasing effect Effects 0.000 claims description 14
- 210000004185 liver Anatomy 0.000 claims description 13
- 210000002216 heart Anatomy 0.000 claims description 12
- 201000002793 renal fibrosis Diseases 0.000 claims description 11
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 10
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 10
- 206010019280 Heart failures Diseases 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 208000006011 Stroke Diseases 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 10
- 125000006413 ring segment Chemical group 0.000 claims description 10
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 9
- 210000004072 lung Anatomy 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- 208000006029 Cardiomegaly Diseases 0.000 claims description 8
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 8
- 210000003734 kidney Anatomy 0.000 claims description 8
- 201000006370 kidney failure Diseases 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 7
- 201000001881 impotence Diseases 0.000 claims description 7
- 230000002093 peripheral effect Effects 0.000 claims description 7
- 208000007536 Thrombosis Diseases 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 208000019423 liver disease Diseases 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
- 208000016621 Hearing disease Diseases 0.000 claims description 5
- 208000019693 Lung disease Diseases 0.000 claims description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
- 208000001435 Thromboembolism Diseases 0.000 claims description 5
- 230000036772 blood pressure Effects 0.000 claims description 5
- 208000030533 eye disease Diseases 0.000 claims description 5
- 208000006454 hepatitis Diseases 0.000 claims description 5
- 231100000283 hepatitis Toxicity 0.000 claims description 5
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 5
- 208000017520 skin disease Diseases 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 206010063985 Phytosterolaemia Diseases 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 208000002227 Sitosterolemia Diseases 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 230000003511 endothelial effect Effects 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000010706 fatty liver disease Diseases 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 201000004384 Alopecia Diseases 0.000 claims description 3
- 206010003694 Atrophy Diseases 0.000 claims description 3
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 3
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 3
- 206010039163 Right ventricular failure Diseases 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 208000037849 arterial hypertension Diseases 0.000 claims description 3
- 230000037444 atrophy Effects 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 230000035876 healing Effects 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000009424 thromboembolic effect Effects 0.000 claims description 3
- 238000012546 transfer Methods 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 231100000360 alopecia Toxicity 0.000 claims description 2
- 210000001736 capillary Anatomy 0.000 claims description 2
- 210000001147 pulmonary artery Anatomy 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 53
- 230000036541 health Effects 0.000 claims 23
- 230000001684 chronic effect Effects 0.000 claims 18
- 206010020772 Hypertension Diseases 0.000 claims 13
- 230000001154 acute effect Effects 0.000 claims 13
- 206010012289 Dementia Diseases 0.000 claims 12
- 208000011580 syndromic disease Diseases 0.000 claims 11
- 206010012601 diabetes mellitus Diseases 0.000 claims 10
- 230000004064 dysfunction Effects 0.000 claims 10
- 230000008085 renal dysfunction Effects 0.000 claims 10
- 238000002054 transplantation Methods 0.000 claims 10
- 208000031229 Cardiomyopathies Diseases 0.000 claims 9
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims 8
- 208000005615 Interstitial Cystitis Diseases 0.000 claims 8
- 208000009525 Myocarditis Diseases 0.000 claims 8
- 208000034189 Sclerosis Diseases 0.000 claims 8
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims 8
- 206010028537 myelofibrosis Diseases 0.000 claims 8
- 201000000306 sarcoidosis Diseases 0.000 claims 8
- 208000010718 Multiple Organ Failure Diseases 0.000 claims 7
- 230000007850 degeneration Effects 0.000 claims 7
- 208000014674 injury Diseases 0.000 claims 7
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims 7
- 208000010125 myocardial infarction Diseases 0.000 claims 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims 6
- 206010014561 Emphysema Diseases 0.000 claims 6
- 206010019196 Head injury Diseases 0.000 claims 6
- 208000000185 Localized scleroderma Diseases 0.000 claims 6
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 6
- 208000012322 Raynaud phenomenon Diseases 0.000 claims 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 6
- 206010047115 Vasculitis Diseases 0.000 claims 6
- 230000001746 atrial effect Effects 0.000 claims 6
- 208000020832 chronic kidney disease Diseases 0.000 claims 6
- 230000006378 damage Effects 0.000 claims 6
- 201000006417 multiple sclerosis Diseases 0.000 claims 6
- 201000011461 pre-eclampsia Diseases 0.000 claims 6
- 230000000750 progressive effect Effects 0.000 claims 6
- 230000001568 sexual effect Effects 0.000 claims 6
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims 5
- 206010011878 Deafness Diseases 0.000 claims 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 5
- 208000005189 Embolism Diseases 0.000 claims 5
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims 5
- 206010008118 cerebral infarction Diseases 0.000 claims 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims 5
- 208000028867 ischemia Diseases 0.000 claims 5
- 201000006938 muscular dystrophy Diseases 0.000 claims 5
- 201000009925 nephrosclerosis Diseases 0.000 claims 5
- 230000002792 vascular Effects 0.000 claims 5
- 230000002861 ventricular Effects 0.000 claims 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 4
- 200000000007 Arterial disease Diseases 0.000 claims 4
- 201000006935 Becker muscular dystrophy Diseases 0.000 claims 4
- 206010006482 Bronchospasm Diseases 0.000 claims 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 4
- 102000008186 Collagen Human genes 0.000 claims 4
- 108010035532 Collagen Proteins 0.000 claims 4
- 208000002330 Congenital Heart Defects Diseases 0.000 claims 4
- 208000011231 Crohn disease Diseases 0.000 claims 4
- 206010011796 Cystitis interstitial Diseases 0.000 claims 4
- 206010013935 Dysmenorrhoea Diseases 0.000 claims 4
- 201000009273 Endometriosis Diseases 0.000 claims 4
- 206010048554 Endothelial dysfunction Diseases 0.000 claims 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 4
- 108010023302 HDL Cholesterol Proteins 0.000 claims 4
- 206010048865 Hypoacusis Diseases 0.000 claims 4
- 208000024934 IgG4-related mediastinitis Diseases 0.000 claims 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 4
- 108010028554 LDL Cholesterol Proteins 0.000 claims 4
- 206010071289 Lower urinary tract symptoms Diseases 0.000 claims 4
- 208000005777 Lupus Nephritis Diseases 0.000 claims 4
- 208000002805 Mediastinal fibrosis Diseases 0.000 claims 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 4
- 206010029164 Nephrotic syndrome Diseases 0.000 claims 4
- 208000008589 Obesity Diseases 0.000 claims 4
- 206010030113 Oedema Diseases 0.000 claims 4
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 claims 4
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 claims 4
- 208000003782 Raynaud disease Diseases 0.000 claims 4
- 206010039710 Scleroderma Diseases 0.000 claims 4
- 206010040047 Sepsis Diseases 0.000 claims 4
- 208000032594 Vascular Remodeling Diseases 0.000 claims 4
- 201000004810 Vascular dementia Diseases 0.000 claims 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 4
- 230000002159 abnormal effect Effects 0.000 claims 4
- 230000035508 accumulation Effects 0.000 claims 4
- 238000009825 accumulation Methods 0.000 claims 4
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 4
- 238000002399 angioplasty Methods 0.000 claims 4
- 206010002906 aortic stenosis Diseases 0.000 claims 4
- 230000037007 arousal Effects 0.000 claims 4
- 230000007885 bronchoconstriction Effects 0.000 claims 4
- 230000000747 cardiac effect Effects 0.000 claims 4
- 229920001436 collagen Polymers 0.000 claims 4
- 208000028831 congenital heart disease Diseases 0.000 claims 4
- 229940109239 creatinine Drugs 0.000 claims 4
- 238000000502 dialysis Methods 0.000 claims 4
- 230000003205 diastolic effect Effects 0.000 claims 4
- 230000008694 endothelial dysfunction Effects 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- 206010025135 lupus erythematosus Diseases 0.000 claims 4
- 201000008383 nephritis Diseases 0.000 claims 4
- 235000020824 obesity Nutrition 0.000 claims 4
- 230000000414 obstructive effect Effects 0.000 claims 4
- 208000007232 portal hypertension Diseases 0.000 claims 4
- 208000028173 post-traumatic stress disease Diseases 0.000 claims 4
- 208000037803 restenosis Diseases 0.000 claims 4
- 201000004409 schistosomiasis Diseases 0.000 claims 4
- 201000000980 schizophrenia Diseases 0.000 claims 4
- 208000007056 sickle cell anemia Diseases 0.000 claims 4
- 230000001732 thrombotic effect Effects 0.000 claims 4
- 239000003053 toxin Substances 0.000 claims 4
- 231100000765 toxin Toxicity 0.000 claims 4
- 108700012359 toxins Proteins 0.000 claims 4
- 208000014001 urinary system disease Diseases 0.000 claims 4
- 210000002700 urine Anatomy 0.000 claims 4
- 208000019553 vascular disease Diseases 0.000 claims 4
- 206010001580 Albuminuria Diseases 0.000 claims 3
- 201000006474 Brain Ischemia Diseases 0.000 claims 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims 3
- 208000007530 Essential hypertension Diseases 0.000 claims 3
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 claims 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims 3
- 206010027525 Microalbuminuria Diseases 0.000 claims 3
- 208000034486 Multi-organ failure Diseases 0.000 claims 3
- 201000001068 Prinzmetal angina Diseases 0.000 claims 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 3
- 208000017442 Retinal disease Diseases 0.000 claims 3
- 206010038923 Retinopathy Diseases 0.000 claims 3
- 208000006673 asthma Diseases 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 239000008280 blood Substances 0.000 claims 3
- 230000002500 effect on skin Effects 0.000 claims 3
- 239000000835 fiber Substances 0.000 claims 3
- 230000002496 gastric effect Effects 0.000 claims 3
- 230000001900 immune effect Effects 0.000 claims 3
- 230000006872 improvement Effects 0.000 claims 3
- 201000010901 lateral sclerosis Diseases 0.000 claims 3
- 230000036244 malformation Effects 0.000 claims 3
- 208000005264 motor neuron disease Diseases 0.000 claims 3
- 244000045947 parasite Species 0.000 claims 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims 3
- 238000007634 remodeling Methods 0.000 claims 3
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 3
- 206010067092 AIDS cholangiopathy Diseases 0.000 claims 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 2
- 208000009304 Acute Kidney Injury Diseases 0.000 claims 2
- 208000003200 Adenoma Diseases 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 208000000044 Amnesia Diseases 0.000 claims 2
- 206010002199 Anaphylactic shock Diseases 0.000 claims 2
- 206010002329 Aneurysm Diseases 0.000 claims 2
- 206010002388 Angina unstable Diseases 0.000 claims 2
- 208000019901 Anxiety disease Diseases 0.000 claims 2
- 206010002915 Aortic valve incompetence Diseases 0.000 claims 2
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims 2
- 206010003175 Arterial spasm Diseases 0.000 claims 2
- 208000002102 Atrial Premature Complexes Diseases 0.000 claims 2
- 206010003662 Atrial flutter Diseases 0.000 claims 2
- 206010003671 Atrioventricular Block Diseases 0.000 claims 2
- 208000006808 Atrioventricular Nodal Reentry Tachycardia Diseases 0.000 claims 2
- 208000004746 Atrophic Vaginitis Diseases 0.000 claims 2
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 claims 2
- 206010061666 Autonomic neuropathy Diseases 0.000 claims 2
- 208000037157 Azotemia Diseases 0.000 claims 2
- 206010004637 Bile duct stone Diseases 0.000 claims 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 2
- 208000020925 Bipolar disease Diseases 0.000 claims 2
- 208000020084 Bone disease Diseases 0.000 claims 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims 2
- 208000004990 Cardiorenal syndrome Diseases 0.000 claims 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims 2
- 206010008635 Cholestasis Diseases 0.000 claims 2
- 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 claims 2
- 208000029147 Collagen-vascular disease Diseases 0.000 claims 2
- 208000004117 Congenital Myasthenic Syndromes Diseases 0.000 claims 2
- 206010010356 Congenital anomaly Diseases 0.000 claims 2
- 206010052895 Coronary artery insufficiency Diseases 0.000 claims 2
- 208000026292 Cystic Kidney disease Diseases 0.000 claims 2
- 208000016192 Demyelinating disease Diseases 0.000 claims 2
- 206010012305 Demyelination Diseases 0.000 claims 2
- 201000004624 Dermatitis Diseases 0.000 claims 2
- 206010054044 Diabetic microangiopathy Diseases 0.000 claims 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 2
- 206010013774 Dry eye Diseases 0.000 claims 2
- 208000001708 Dupuytren contracture Diseases 0.000 claims 2
- 241000792859 Enema Species 0.000 claims 2
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims 2
- 208000004930 Fatty Liver Diseases 0.000 claims 2
- 206010057671 Female sexual dysfunction Diseases 0.000 claims 2
- 102000008946 Fibrinogen Human genes 0.000 claims 2
- 108010049003 Fibrinogen Proteins 0.000 claims 2
- 208000010412 Glaucoma Diseases 0.000 claims 2
- 208000022461 Glomerular disease Diseases 0.000 claims 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 2
- 206010018691 Granuloma Diseases 0.000 claims 2
- 208000024815 Granulomatous liver disease Diseases 0.000 claims 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims 2
- 206010063629 Hippocampal sclerosis Diseases 0.000 claims 2
- 208000023105 Huntington disease Diseases 0.000 claims 2
- 206010020575 Hyperammonaemia Diseases 0.000 claims 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- 206010020852 Hypertonia Diseases 0.000 claims 2
- 206010020853 Hypertonic bladder Diseases 0.000 claims 2
- 206010021024 Hypolipidaemia Diseases 0.000 claims 2
- 206010021036 Hyponatraemia Diseases 0.000 claims 2
- 206010058558 Hypoperfusion Diseases 0.000 claims 2
- 208000001953 Hypotension Diseases 0.000 claims 2
- 206010021133 Hypoventilation Diseases 0.000 claims 2
- 206010021143 Hypoxia Diseases 0.000 claims 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 2
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 claims 2
- 206010061216 Infarction Diseases 0.000 claims 2
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 2
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 claims 2
- 208000002260 Keloid Diseases 0.000 claims 2
- 206010023330 Keloid scar Diseases 0.000 claims 2
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 claims 2
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims 2
- 206010024119 Left ventricular failure Diseases 0.000 claims 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims 2
- 201000002832 Lewy body dementia Diseases 0.000 claims 2
- 102000003960 Ligases Human genes 0.000 claims 2
- 108090000364 Ligases Proteins 0.000 claims 2
- 208000026139 Memory disease Diseases 0.000 claims 2
- 208000019695 Migraine disease Diseases 0.000 claims 2
- 208000020128 Mitral stenosis Diseases 0.000 claims 2
- 208000011682 Mitral valve disease Diseases 0.000 claims 2
- 206010027727 Mitral valve incompetence Diseases 0.000 claims 2
- 206010027982 Morphoea Diseases 0.000 claims 2
- 208000001089 Multiple system atrophy Diseases 0.000 claims 2
- 206010028594 Myocardial fibrosis Diseases 0.000 claims 2
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 claims 2
- 206010029279 Neurogenic bladder Diseases 0.000 claims 2
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 claims 2
- 208000007256 Nevus Diseases 0.000 claims 2
- 201000000023 Osteosclerosis Diseases 0.000 claims 2
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010033645 Pancreatitis Diseases 0.000 claims 2
- 206010033799 Paralysis Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000000450 Pelvic Pain Diseases 0.000 claims 2
- 208000004362 Penile Induration Diseases 0.000 claims 2
- 206010061340 Peripheral embolism Diseases 0.000 claims 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 2
- 208000020758 Peyronie disease Diseases 0.000 claims 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 2
- 208000000418 Premature Cardiac Complexes Diseases 0.000 claims 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 2
- 208000032319 Primary lateral sclerosis Diseases 0.000 claims 2
- 206010036805 Progressive massive fibrosis Diseases 0.000 claims 2
- 206010037457 Pulmonary vasculitis Diseases 0.000 claims 2
- 206010037596 Pyelonephritis Diseases 0.000 claims 2
- 208000033626 Renal failure acute Diseases 0.000 claims 2
- 206010062237 Renal impairment Diseases 0.000 claims 2
- 206010063837 Reperfusion injury Diseases 0.000 claims 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 2
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 claims 2
- 201000004239 Secondary hypertension Diseases 0.000 claims 2
- 206010040070 Septic Shock Diseases 0.000 claims 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims 2
- 206010065342 Supraventricular tachyarrhythmia Diseases 0.000 claims 2
- 208000001871 Tachycardia Diseases 0.000 claims 2
- 208000009205 Tinnitus Diseases 0.000 claims 2
- 208000018452 Torsade de pointes Diseases 0.000 claims 2
- 208000002363 Torsades de Pointes Diseases 0.000 claims 2
- 206010044221 Toxic encephalopathy Diseases 0.000 claims 2
- 231100000076 Toxic encephalopathy Toxicity 0.000 claims 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 2
- 201000001943 Tricuspid Valve Insufficiency Diseases 0.000 claims 2
- 206010044640 Tricuspid valve incompetence Diseases 0.000 claims 2
- 206010044642 Tricuspid valve stenosis Diseases 0.000 claims 2
- 208000007814 Unstable Angina Diseases 0.000 claims 2
- 206010046298 Upper motor neurone lesion Diseases 0.000 claims 2
- 208000026723 Urinary tract disease Diseases 0.000 claims 2
- 208000012931 Urologic disease Diseases 0.000 claims 2
- 206010058990 Venous occlusion Diseases 0.000 claims 2
- 208000008131 Ventricular Flutter Diseases 0.000 claims 2
- 208000009729 Ventricular Premature Complexes Diseases 0.000 claims 2
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims 2
- 206010065341 Ventricular tachyarrhythmia Diseases 0.000 claims 2
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 claims 2
- 201000008803 Wolff-Parkinson-white syndrome Diseases 0.000 claims 2
- 230000005856 abnormality Effects 0.000 claims 2
- 201000011040 acute kidney failure Diseases 0.000 claims 2
- 206010069351 acute lung injury Diseases 0.000 claims 2
- 201000005180 acute myocarditis Diseases 0.000 claims 2
- 208000012998 acute renal failure Diseases 0.000 claims 2
- 239000000853 adhesive Substances 0.000 claims 2
- 230000001070 adhesive effect Effects 0.000 claims 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 2
- 230000002776 aggregation Effects 0.000 claims 2
- 238000004220 aggregation Methods 0.000 claims 2
- 230000001476 alcoholic effect Effects 0.000 claims 2
- 208000033571 alveolar capillary dysplasia with misalignment of pulmonary veins Diseases 0.000 claims 2
- 208000003455 anaphylaxis Diseases 0.000 claims 2
- 208000007502 anemia Diseases 0.000 claims 2
- 230000036506 anxiety Effects 0.000 claims 2
- 201000002064 aortic valve insufficiency Diseases 0.000 claims 2
- 206010003119 arrhythmia Diseases 0.000 claims 2
- 230000006793 arrhythmia Effects 0.000 claims 2
- 210000002565 arteriole Anatomy 0.000 claims 2
- 206010003246 arthritis Diseases 0.000 claims 2
- 230000003143 atherosclerotic effect Effects 0.000 claims 2
- 230000005784 autoimmunity Effects 0.000 claims 2
- 210000004227 basal ganglia Anatomy 0.000 claims 2
- 208000010217 blepharitis Diseases 0.000 claims 2
- 230000017531 blood circulation Effects 0.000 claims 2
- 208000015294 blood coagulation disease Diseases 0.000 claims 2
- 230000036765 blood level Effects 0.000 claims 2
- 230000004097 bone metabolism Effects 0.000 claims 2
- 206010006451 bronchitis Diseases 0.000 claims 2
- 230000023852 carbohydrate metabolic process Effects 0.000 claims 2
- 235000021256 carbohydrate metabolism Nutrition 0.000 claims 2
- 206010007625 cardiogenic shock Diseases 0.000 claims 2
- 230000020411 cell activation Effects 0.000 claims 2
- 210000003169 central nervous system Anatomy 0.000 claims 2
- 230000002490 cerebral effect Effects 0.000 claims 2
- 230000003788 cerebral perfusion Effects 0.000 claims 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- 208000007451 chronic bronchitis Diseases 0.000 claims 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 230000006835 compression Effects 0.000 claims 2
- 238000007906 compression Methods 0.000 claims 2
- 208000018631 connective tissue disease Diseases 0.000 claims 2
- 230000008602 contraction Effects 0.000 claims 2
- 239000002872 contrast media Substances 0.000 claims 2
- 238000007887 coronary angioplasty Methods 0.000 claims 2
- 230000008021 deposition Effects 0.000 claims 2
- 201000009101 diabetic angiopathy Diseases 0.000 claims 2
- 208000010643 digestive system disease Diseases 0.000 claims 2
- 208000016097 disease of metabolism Diseases 0.000 claims 2
- 230000005750 disease progression Effects 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000007920 enema Substances 0.000 claims 2
- 229940095399 enema Drugs 0.000 claims 2
- 230000029142 excretion Effects 0.000 claims 2
- 229940012952 fibrinogen Drugs 0.000 claims 2
- 230000003176 fibrotic effect Effects 0.000 claims 2
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims 2
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 claims 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 2
- 230000001434 glomerular Effects 0.000 claims 2
- 206010061989 glomerulosclerosis Diseases 0.000 claims 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 2
- 208000024908 graft versus host disease Diseases 0.000 claims 2
- 208000019622 heart disease Diseases 0.000 claims 2
- 210000003709 heart valve Anatomy 0.000 claims 2
- 208000007386 hepatic encephalopathy Diseases 0.000 claims 2
- 210000004024 hepatic stellate cell Anatomy 0.000 claims 2
- 201000005991 hyperphosphatemia Diseases 0.000 claims 2
- 230000001631 hypertensive effect Effects 0.000 claims 2
- 230000001969 hypertrophic effect Effects 0.000 claims 2
- 208000026621 hypolipoproteinemia Diseases 0.000 claims 2
- 230000036543 hypotension Effects 0.000 claims 2
- 208000018875 hypoxemia Diseases 0.000 claims 2
- 230000007574 infarction Effects 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims 2
- 208000001286 intracranial vasospasm Diseases 0.000 claims 2
- 208000001024 intrahepatic cholestasis Diseases 0.000 claims 2
- 230000007872 intrahepatic cholestasis Effects 0.000 claims 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims 2
- 210000001117 keloid Anatomy 0.000 claims 2
- 230000003902 lesion Effects 0.000 claims 2
- 210000000265 leukocyte Anatomy 0.000 claims 2
- 230000006372 lipid accumulation Effects 0.000 claims 2
- 206010025005 lumbar spinal stenosis Diseases 0.000 claims 2
- 230000036210 malignancy Effects 0.000 claims 2
- 230000003211 malignant effect Effects 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 210000001161 mammalian embryo Anatomy 0.000 claims 2
- 201000001231 mediastinitis Diseases 0.000 claims 2
- 230000006984 memory degeneration Effects 0.000 claims 2
- 206010027175 memory impairment Diseases 0.000 claims 2
- 208000023060 memory loss Diseases 0.000 claims 2
- 206010027599 migraine Diseases 0.000 claims 2
- 230000005012 migration Effects 0.000 claims 2
- 238000013508 migration Methods 0.000 claims 2
- 208000006887 mitral valve stenosis Diseases 0.000 claims 2
- 210000001616 monocyte Anatomy 0.000 claims 2
- 210000003205 muscle Anatomy 0.000 claims 2
- 208000031225 myocardial ischemia Diseases 0.000 claims 2
- 230000001338 necrotic effect Effects 0.000 claims 2
- 210000000653 nervous system Anatomy 0.000 claims 2
- 230000004112 neuroprotection Effects 0.000 claims 2
- 210000000056 organ Anatomy 0.000 claims 2
- 206010033103 otosclerosis Diseases 0.000 claims 2
- 208000020629 overactive bladder Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 230000008447 perception Effects 0.000 claims 2
- 230000010412 perfusion Effects 0.000 claims 2
- 206010034674 peritonitis Diseases 0.000 claims 2
- 230000035699 permeability Effects 0.000 claims 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims 2
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 claims 2
- 229910052700 potassium Inorganic materials 0.000 claims 2
- 239000011591 potassium Substances 0.000 claims 2
- 230000035935 pregnancy Effects 0.000 claims 2
- 206010036596 premature ejaculation Diseases 0.000 claims 2
- 208000003476 primary myelofibrosis Diseases 0.000 claims 2
- 201000000742 primary sclerosing cholangitis Diseases 0.000 claims 2
- 230000035755 proliferation Effects 0.000 claims 2
- 210000002307 prostate Anatomy 0.000 claims 2
- 208000014731 pulmonary artery disease Diseases 0.000 claims 2
- 208000009138 pulmonary valve stenosis Diseases 0.000 claims 2
- 208000037813 pulmonary venous hypertension Diseases 0.000 claims 2
- 208000030390 pulmonic stenosis Diseases 0.000 claims 2
- 230000010451 regulation of platelet aggregation Effects 0.000 claims 2
- 230000000241 respiratory effect Effects 0.000 claims 2
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 2
- 231100000241 scar Toxicity 0.000 claims 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims 2
- 230000002784 sclerotic effect Effects 0.000 claims 2
- 208000037812 secondary pulmonary hypertension Diseases 0.000 claims 2
- 230000036303 septic shock Effects 0.000 claims 2
- 230000035939 shock Effects 0.000 claims 2
- 230000007958 sleep Effects 0.000 claims 2
- 201000002859 sleep apnea Diseases 0.000 claims 2
- 230000000391 smoking effect Effects 0.000 claims 2
- 210000002460 smooth muscle Anatomy 0.000 claims 2
- 208000002320 spinal muscular atrophy Diseases 0.000 claims 2
- 208000005198 spinal stenosis Diseases 0.000 claims 2
- 210000004003 subcutaneous fat Anatomy 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 206010042772 syncope Diseases 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- 230000006794 tachycardia Effects 0.000 claims 2
- 230000000542 thalamic effect Effects 0.000 claims 2
- 201000002931 third-degree atrioventricular block Diseases 0.000 claims 2
- 230000002537 thrombolytic effect Effects 0.000 claims 2
- 231100000886 tinnitus Toxicity 0.000 claims 2
- 208000037816 tissue injury Diseases 0.000 claims 2
- 230000008733 trauma Effects 0.000 claims 2
- 230000009529 traumatic brain injury Effects 0.000 claims 2
- 210000005239 tubule Anatomy 0.000 claims 2
- 208000009852 uremia Diseases 0.000 claims 2
- 206010046459 urethral obstruction Diseases 0.000 claims 2
- 210000002229 urogenital system Anatomy 0.000 claims 2
- 208000037820 vascular cognitive impairment Diseases 0.000 claims 2
- 208000003663 ventricular fibrillation Diseases 0.000 claims 2
- 206010047302 ventricular tachycardia Diseases 0.000 claims 2
- 206010047470 viral myocarditis Diseases 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 claims 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 claims 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 206010001233 Adenoma benign Diseases 0.000 claims 1
- 206010002153 Anal fissure Diseases 0.000 claims 1
- 208000016583 Anus disease Diseases 0.000 claims 1
- 206010003178 Arterial thrombosis Diseases 0.000 claims 1
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
- 206010004593 Bile duct cancer Diseases 0.000 claims 1
- 208000006386 Bone Resorption Diseases 0.000 claims 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims 1
- 206010011903 Deafness traumatic Diseases 0.000 claims 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 claims 1
- 208000002249 Diabetes Complications Diseases 0.000 claims 1
- 206010012655 Diabetic complications Diseases 0.000 claims 1
- 208000008960 Diabetic foot Diseases 0.000 claims 1
- 206010056340 Diabetic ulcer Diseases 0.000 claims 1
- 206010052337 Diastolic dysfunction Diseases 0.000 claims 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims 1
- 208000030814 Eating disease Diseases 0.000 claims 1
- 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
- 208000009531 Fissure in Ano Diseases 0.000 claims 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 claims 1
- 208000002682 Hyperkalemia Diseases 0.000 claims 1
- 206010020880 Hypertrophy Diseases 0.000 claims 1
- 206010021639 Incontinence Diseases 0.000 claims 1
- 206010022562 Intermittent claudication Diseases 0.000 claims 1
- 206010023439 Kidney transplant rejection Diseases 0.000 claims 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 claims 1
- 206010025219 Lymphangioma Diseases 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 208000016285 Movement disease Diseases 0.000 claims 1
- 208000002038 Muscle Hypertonia Diseases 0.000 claims 1
- 206010028289 Muscle atrophy Diseases 0.000 claims 1
- 208000029578 Muscle disease Diseases 0.000 claims 1
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 1
- 208000002946 Noise-Induced Hearing Loss Diseases 0.000 claims 1
- 206010053159 Organ failure Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000007542 Paresis Diseases 0.000 claims 1
- 206010034487 Pericarditis constrictive Diseases 0.000 claims 1
- 206010065159 Polychondritis Diseases 0.000 claims 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 claims 1
- 206010051482 Prostatomegaly Diseases 0.000 claims 1
- 206010038423 Renal cyst Diseases 0.000 claims 1
- 206010038934 Retinopathy proliferative Diseases 0.000 claims 1
- 201000007981 Reye syndrome Diseases 0.000 claims 1
- 208000007718 Stable Angina Diseases 0.000 claims 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 claims 1
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 1
- 206010042953 Systemic sclerosis Diseases 0.000 claims 1
- 206010071436 Systolic dysfunction Diseases 0.000 claims 1
- 208000001163 Tangier disease Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 208000025609 Urogenital disease Diseases 0.000 claims 1
- 206010067269 Uterine fibrosis Diseases 0.000 claims 1
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 1
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims 1
- 206010047249 Venous thrombosis Diseases 0.000 claims 1
- 206010048215 Xanthomatosis Diseases 0.000 claims 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 claims 1
- 201000003554 argininosuccinic aciduria Diseases 0.000 claims 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 claims 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 claims 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 claims 1
- 208000026900 bile duct neoplasm Diseases 0.000 claims 1
- 230000005540 biological transmission Effects 0.000 claims 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 1
- 210000004204 blood vessel Anatomy 0.000 claims 1
- 230000010072 bone remodeling Effects 0.000 claims 1
- 230000024279 bone resorption Effects 0.000 claims 1
- 208000001969 capillary hemangioma Diseases 0.000 claims 1
- 230000003683 cardiac damage Effects 0.000 claims 1
- 206010061592 cardiac fibrillation Diseases 0.000 claims 1
- 208000006990 cholangiocarcinoma Diseases 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- 208000000839 constrictive pericarditis Diseases 0.000 claims 1
- 230000001186 cumulative effect Effects 0.000 claims 1
- 231100000895 deafness Toxicity 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 201000001981 dermatomyositis Diseases 0.000 claims 1
- 230000010339 dilation Effects 0.000 claims 1
- 235000014632 disordered eating Nutrition 0.000 claims 1
- 201000009338 distal myopathy Diseases 0.000 claims 1
- 201000006549 dyspepsia Diseases 0.000 claims 1
- 239000003792 electrolyte Substances 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 230000002600 fibrillogenic effect Effects 0.000 claims 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims 1
- 210000001652 frontal lobe Anatomy 0.000 claims 1
- 208000024963 hair loss Diseases 0.000 claims 1
- 230000003676 hair loss Effects 0.000 claims 1
- 208000016354 hearing loss disease Diseases 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 230000028709 inflammatory response Effects 0.000 claims 1
- 208000021156 intermittent vascular claudication Diseases 0.000 claims 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 230000028252 learning or memory Effects 0.000 claims 1
- 201000010260 leiomyoma Diseases 0.000 claims 1
- 210000002751 lymph Anatomy 0.000 claims 1
- 239000012528 membrane Substances 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 230000004089 microcirculation Effects 0.000 claims 1
- 208000027061 mild cognitive impairment Diseases 0.000 claims 1
- 230000020763 muscle atrophy Effects 0.000 claims 1
- 201000000585 muscular atrophy Diseases 0.000 claims 1
- 230000002107 myocardial effect Effects 0.000 claims 1
- 210000004165 myocardium Anatomy 0.000 claims 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 claims 1
- 201000001119 neuropathy Diseases 0.000 claims 1
- 230000007823 neuropathy Effects 0.000 claims 1
- 230000008816 organ damage Effects 0.000 claims 1
- 230000011164 ossification Effects 0.000 claims 1
- 210000002997 osteoclast Anatomy 0.000 claims 1
- 230000024241 parasitism Effects 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 208000005987 polymyositis Diseases 0.000 claims 1
- 230000036316 preload Effects 0.000 claims 1
- 230000002028 premature Effects 0.000 claims 1
- 201000008312 primary pulmonary hypertension Diseases 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 claims 1
- 201000004240 prostatic hypertrophy Diseases 0.000 claims 1
- 210000003102 pulmonary valve Anatomy 0.000 claims 1
- 201000010298 pulmonary valve insufficiency Diseases 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 230000010410 reperfusion Effects 0.000 claims 1
- 208000015658 resistant hypertension Diseases 0.000 claims 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 claims 1
- 229950005143 sitosterol Drugs 0.000 claims 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 claims 1
- 235000015500 sitosterol Nutrition 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 230000007863 steatosis Effects 0.000 claims 1
- 238000003860 storage Methods 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
- 125000004306 triazinyl group Chemical group 0.000 claims 1
- 208000009999 tuberous sclerosis Diseases 0.000 claims 1
- 231100000397 ulcer Toxicity 0.000 claims 1
- 210000003462 vein Anatomy 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 description 34
- 125000005647 linker group Chemical group 0.000 description 16
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 14
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 14
- 125000003342 alkenyl group Chemical group 0.000 description 14
- 150000001721 carbon Chemical group 0.000 description 13
- 125000004122 cyclic group Chemical group 0.000 description 12
- 239000000126 substance Substances 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 8
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 239000011593 sulfur Substances 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 5
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000004104 aryloxy group Chemical group 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940127296 soluble guanylate cyclase stimulator Drugs 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 230000004648 relaxation of smooth muscle Effects 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- 208000012201 sexual and gender identity disease Diseases 0.000 description 3
- 208000015891 sexual disease Diseases 0.000 description 3
- 239000000021 stimulant Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 2
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 2
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 2
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002431 aminoalkoxy group Chemical group 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
- 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 2
- 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 2
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 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 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
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical compound C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- FSUYMKXZLQOFQY-UHFFFAOYSA-N 3,4-dihydro-1,2-benzodithiine Chemical compound C1=CC=C2SSCCC2=C1 FSUYMKXZLQOFQY-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- ZCFFYALKHPIRKJ-UHFFFAOYSA-N 3-[18-(2-carboxylatoethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethyl-22,23-dihydroporphyrin-21,24-diium-2-yl]propanoate Chemical group N1C(C=C2C(=C(C)C(=CC=3C(C)=C(CCC(O)=O)C(N=3)=C3)N2)C=C)=C(C)C(C=C)=C1C=C1C(C)=C(CCC(O)=O)C3=N1 ZCFFYALKHPIRKJ-UHFFFAOYSA-N 0.000 description 1
- XSFVAQRSZSENGO-UHFFFAOYSA-N 3-benzyl-2h-indazole Chemical compound N1N=C2C=CC=CC2=C1CC1=CC=CC=C1 XSFVAQRSZSENGO-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000021663 Female sexual arousal disease Diseases 0.000 description 1
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 102000006538 Nitric Oxide Synthase Type I Human genes 0.000 description 1
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 1
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 1
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000005082 alkoxyalkenyl group Chemical group 0.000 description 1
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005157 alkyl carboxy group Chemical group 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000005021 aminoalkenyl group Chemical group 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000006515 benzyloxy alkyl group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 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
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 210000005226 corpus cavernosum Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000005159 cyanoalkoxy group Chemical group 0.000 description 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 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
- 229960001123 epoprostenol Drugs 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 125000000262 haloalkenyl group Chemical group 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
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000005114 heteroarylalkoxy group Chemical group 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
- 125000005020 hydroxyalkenyl group Chemical group 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910001959 inorganic nitrate Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002823 nitrates Chemical class 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
- 125000005593 norbornanyl group Chemical group 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000018052 penile erection Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
- 210000003492 pulmonary vein Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 208000037905 systemic hypertension Diseases 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462051576P | 2014-09-17 | 2014-09-17 | |
| US62/051,576 | 2014-09-17 | ||
| US201562204698P | 2015-08-13 | 2015-08-13 | |
| US62/204,698 | 2015-08-13 | ||
| PCT/US2015/050467 WO2016044446A2 (en) | 2014-09-17 | 2015-09-16 | Sgc stimulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017527604A true JP2017527604A (ja) | 2017-09-21 |
| JP2017527604A5 JP2017527604A5 (enExample) | 2018-10-25 |
Family
ID=54291601
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017515197A Withdrawn JP2017527604A (ja) | 2014-09-17 | 2015-09-16 | ｓＧＣ刺激剤 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10844064B2 (enExample) |
| EP (1) | EP3194386A2 (enExample) |
| JP (1) | JP2017527604A (enExample) |
| CN (1) | CN107406421A (enExample) |
| AU (1) | AU2015317823A1 (enExample) |
| CA (1) | CA2961489A1 (enExample) |
| IL (1) | IL251113A0 (enExample) |
| MX (1) | MX2017003518A (enExample) |
| WO (1) | WO2016044446A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021515018A (ja) * | 2018-03-07 | 2021-06-17 | サイクレリオン・セラピューティクス，インコーポレーテッド | 可溶性グアニル酸シクラーゼ刺激薬を調製するための方法 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10513524B2 (en) | 2015-07-07 | 2019-12-24 | H. Lundbeck A/S | PDE9 inhibitors with imidazo triazinone backbone and imidazo pyrazinone backbone for treatment of peripheral diseases |
| CA3006764A1 (en) | 2015-12-14 | 2017-06-22 | Ironwood Pharmaceuticals, Inc. | Use of sgc stimulators for the treatment of gastrointestinal sphincter dysfunction |
| WO2017107052A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase stimulators |
| CN105859726B (zh) * | 2016-05-18 | 2018-07-13 | 南京富润凯德生物医药有限公司 | 一种嘧啶并环中选择性脱卤素的方法 |
| EA201990237A1 (ru) | 2016-07-07 | 2019-08-30 | Сайклерион Терапьютикс, Инк. | Новые способы получения стимуляторов растворимой гуанилатциклазы |
| CR20220309A (es) * | 2016-09-02 | 2022-09-16 | Cyclerion Therapeutics Inc | Estimuladores de sgc |
| EP3525778A1 (de) | 2016-10-11 | 2019-08-21 | Bayer Pharma Aktiengesellschaft | Kombination enthaltend sgc aktivatoren und mineralocorticoid-rezeptor-antagonisten |
| EP3525779B1 (de) | 2016-10-11 | 2024-06-05 | Bayer Pharma Aktiengesellschaft | Kombination enthaltend den sgc stimulator vericuguat und den mineralcorticoid-rezeptor-antagonist finerenone |
| US20190381039A1 (en) | 2016-12-13 | 2019-12-19 | Cyclerion Therapeutics, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS |
| WO2019030358A1 (en) | 2017-08-11 | 2019-02-14 | Syngenta Participations Ag | ACTIVE PYRAZOLE DERIVATIVES ON THE PESTICIDE PLAN |
| AR112673A1 (es) | 2017-08-11 | 2019-11-27 | Syngenta Participations Ag | Derivados de pirazol activos como plaguicidas |
| US20200288713A1 (en) | 2017-08-11 | 2020-09-17 | Syngenta Participations Ag | Pesticidally active pyrazole derivatives |
| WO2019081456A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Aktiengesellschaft | USE OF SGC ACTIVATORS AND STIMULATORS COMPRISING A BETA2 SUBUNIT |
| EP3498298A1 (en) | 2017-12-15 | 2019-06-19 | Bayer AG | The use of sgc stimulators and sgc activators alone or in combination with pde5 inhibitors for the treatment of bone disorders including osteogenesis imperfecta (oi) |
| MX2023004855A (es) | 2018-03-07 | 2023-11-24 | Cyclerion Therapeutics Inc | Formas cristalinas de un estimulante de la guanilil ciclasa soluble (sgc). |
| JP7314173B2 (ja) | 2018-04-30 | 2023-07-25 | バイエル アクチェンゲゼルシャフト | 認知障害の治療のためのｓＧＣ活性化薬及びｓＧＣ刺激薬の使用 |
| MX2020012230A (es) | 2018-05-15 | 2021-01-29 | Bayer Ag | Uso de benzamidas sustituidas con 1,3-tiazol-2-ilo para el tratamiento de enfermedades asociadas con la sensibilizacion de las fibras nerviosas. |
| EP3574905A1 (en) | 2018-05-30 | 2019-12-04 | Adverio Pharma GmbH | Method of identifying a subgroup of patients suffering from dcssc which benefits from a treatment with sgc stimulators and sgc activators in a higher degree than a control group |
| KR20210031931A (ko) | 2018-07-11 | 2021-03-23 | 사이클리온 테라퓨틱스, 인크. | 미토콘드리아 장애의 치료를 위한 sGC 자극제의 용도 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| EP3911675A1 (en) | 2019-01-17 | 2021-11-24 | Bayer Aktiengesellschaft | Methods to determine whether a subject is suitable of being treated with an agonist of soluble guanylyl cyclase (sgc) |
| WO2020164994A1 (en) | 2019-02-13 | 2020-08-20 | Syngenta Crop Protection Ag | Pesticidally active pyrazole derivatives |
| US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| BR112022002698A2 (pt) | 2019-08-14 | 2022-07-19 | Incyte Corp | Compostos de imidazolil pirimidinilamina como inibidores de cdk2 |
| MX2022004390A (es) | 2019-10-11 | 2022-08-08 | Incyte Corp | Aminas biciclicas como inhibidores de la cinasa dependiente de ciclina 2 (cdk2). |
| CN111423377B (zh) * | 2020-05-12 | 2021-06-01 | 中国药科大学 | 5-氨基-1h-吡唑衍生物、制备方法及医药用途 |
| IL302423A (en) * | 2020-10-27 | 2023-06-01 | Cardurion Pharmaceuticals Inc | Pde9 inhibitors for treating cardiac failure |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| WO2025102245A1 (zh) * | 2023-11-14 | 2025-05-22 | 浙江天宇药业股份有限公司 | 一种双重内皮素受体拮抗剂阿普昔腾坦的合成方法 |
Family Cites Families (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US3995631A (en) | 1971-01-13 | 1976-12-07 | Alza Corporation | Osmotic dispenser with means for dispensing active agent responsive to osmotic gradient |
| US4203440A (en) | 1978-10-23 | 1980-05-20 | Alza Corporation | Device having variable volume chamber for dispensing useful agent |
| US4627850A (en) | 1983-11-02 | 1986-12-09 | Alza Corporation | Osmotic capsule |
| EP0192963B1 (de) | 1985-02-27 | 1988-07-20 | Werkzeugmaschinenfabrik Oerlikon-Bührle AG | Schwingungsmesseinrichtung für ein Spiralkegelradgetriebe auf einer Zahnradprüfmaschine |
| IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Dispensing devices powered by hydrogel |
| US5721365A (en) | 1989-09-15 | 1998-02-24 | Us Health | N-substituted piperazine NONOates |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5324280A (en) | 1990-04-02 | 1994-06-28 | Alza Corporation | Osmotic dosage system for delivering a formulation comprising liquid carrier and drug |
| US5155137A (en) | 1990-09-20 | 1992-10-13 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Complexes of nitric oxide with polyamines |
| EP0605622B1 (en) | 1991-09-24 | 1997-11-12 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Oxygen substituted derivatives of nucleophile-nitric oxide adducts as nitric oxide donor prodrugs |
| GB9127531D0 (en) | 1991-12-31 | 1992-02-19 | Fujisawa Pharmaceutical Co | Heterocyclic compound |
| US5814666A (en) | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
| US5691423A (en) | 1992-08-24 | 1997-11-25 | The United States Of America As Represented By The Department Of Health And Human Services | Polysaccharide-bound nitric oxide-nucleophile adducts |
| US5910316A (en) | 1992-08-24 | 1999-06-08 | The United States Of America, As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents to treat impotency |
| US5405919A (en) | 1992-08-24 | 1995-04-11 | The United States Of America As Represented By The Secretary Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions and methods of treating biological disorders |
| US5632981A (en) | 1992-08-24 | 1997-05-27 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| AU685178B2 (en) | 1993-10-08 | 1998-01-15 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Use of nitric oxide-releasing compounds as hypoxic cell radiation sensitizers |
| JP2928079B2 (ja) | 1994-02-14 | 1999-07-28 | 永信薬品工業股▲ふん▼有限公司 | １−（置換ベンジル）−３−（置換アリール）縮合ピラゾール類、その製造法及びその用途 |
| US5700830A (en) | 1994-11-22 | 1997-12-23 | The United States Of America As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents for reducing metastasis risk |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| DK0837052T3 (da) | 1995-06-21 | 2007-01-02 | Shionogi & Co | Bicykliske aminoderivater og PGD2-antagonist indeholdende disse |
| US5714511A (en) | 1995-07-31 | 1998-02-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Selective prevention of organ injury in sepsis and shock using selection release of nitric oxide in vulnerable organs |
| WO1998025915A1 (en) | 1996-12-12 | 1998-06-18 | Shionogi & Co., Ltd. | Fused heterocyclic benzenecarboxylic acid amide derivatives and pgd2 antagonists containing the same |
| EP0944614B1 (en) | 1996-12-13 | 2002-09-11 | Shionogi & Co., Ltd. | Benzothiophenecarboxamide derivatives and pgd2 antagonists comprising them |
| DE19744026A1 (de) | 1997-10-06 | 1999-04-08 | Hoechst Marion Roussel De Gmbh | Pyrazol-Derivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| HU228111B1 (en) | 1998-07-08 | 2012-11-28 | Sanofi Aventis Deutschland | Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them |
| DE19830430A1 (de) | 1998-07-08 | 2000-01-13 | Hoechst Marion Roussel De Gmbh | Schwefelsubstituierte Sulfonylamino-carbonsäure-N-arylamide, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
| CN1161101C (zh) | 1998-12-17 | 2004-08-11 | 阿尔扎有限公司 | 用多层包衣将填充液体的明胶胶囊转变成控制释放的系统 |
| US6342249B1 (en) | 1998-12-23 | 2002-01-29 | Alza Corporation | Controlled release liquid active agent formulation dosage forms |
| DE19942809A1 (de) | 1999-09-08 | 2001-03-15 | Bayer Ag | Verfahren zur Herstellung substituierter Pyrimidinderivate |
| DE19943635A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| WO2003022814A1 (en) | 2001-09-07 | 2003-03-20 | Ono Pharmaceutical Co., Ltd. | Indole derivatives |
| DE60115411D1 (de) | 2000-04-12 | 2006-01-05 | Merck Frosst Canada & Co Kirkl | Verfahren und zusammensetzungen zur behandlung von allergischen zuständen mit pgd2 rezeptor antagonisten |
| US20010051624A1 (en) | 2000-04-12 | 2001-12-13 | Jones Thomas R. | Method and compositions for the treatment of allergic conditions using PGD2 receptor antagonists |
| US6878522B2 (en) | 2000-07-07 | 2005-04-12 | Baiyong Li | Methods for the identification of compounds useful for the treatment of disease states mediated by prostaglandin D2 |
| MY136316A (en) | 2001-02-13 | 2008-09-30 | Sanofi Aventis Deutschland | Acylated 6,7,8,9-tetrahydro-5h-benzocycloheptenyl amines and their use as pharmaceutical. |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| PE20020856A1 (es) | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
| TWI241190B (en) | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
| US6511911B1 (en) | 2001-04-03 | 2003-01-28 | Advanced Micro Devices, Inc. | Metal gate stack with etch stop layer |
| WO2003022813A1 (en) | 2001-09-07 | 2003-03-20 | Ono Pharmaceutical Co., Ltd. | Indole derivatives, process for producing the same and drugs containing the same as the active ingredient |
| US6806380B2 (en) | 2001-10-02 | 2004-10-19 | Lexicon Pharmaceuticals, Inc. | Modified safe and efficient process for the environmentally friendly synthesis of imidoesters |
| SE0200411D0 (sv) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| SE0200356D0 (sv) | 2002-02-05 | 2002-02-05 | Astrazeneca Ab | Novel use |
| DE10216145A1 (de) | 2002-04-12 | 2003-10-23 | Bayer Ag | Verwendung von Stimulatoren der löslichen Guanylatcyclase zur Behandlung von Glaukom |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| US7534897B2 (en) | 2002-05-16 | 2009-05-19 | Shionogi & Co., Ltd. | Indole arylsulfonaimide compounds exhibiting PGD 2 receptor antagonism |
| WO2003097042A1 (en) | 2002-05-16 | 2003-11-27 | Shionogi & Co., Ltd. | Pgd2 receptor antagonist |
| TW200307542A (en) | 2002-05-30 | 2003-12-16 | Astrazeneca Ab | Novel compounds |
| SE0201635D0 (sv) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
| SE0202241D0 (sv) | 2002-07-17 | 2002-07-17 | Astrazeneca Ab | Novel Compounds |
| KR20050055747A (ko) | 2002-10-04 | 2005-06-13 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 염증 질환 치료용의 ｐｇｄ2 수용체 길항제 |
| EP1585511B1 (en) | 2002-12-20 | 2013-01-23 | Amgen Inc. | Asthma and allergic inflammation modulators |
| JP2006517234A (ja) | 2003-02-10 | 2006-07-20 | アムジエン・インコーポレーテツド | バニロイド受容体リガンドおよび治療におけるこれらのリガンドの使用 |
| TW200423930A (en) | 2003-02-18 | 2004-11-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitors |
| KR20060033033A (ko) | 2003-08-04 | 2006-04-18 | 화이자 프로덕츠 인크. | 콜레스테릴 에스테르 전달 단백질 억제제의 제어 방출 및ｈｍｇ-ｃｏａ 리덕타제 억제제의 순간 방출을 제공하는제형 |
| UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
| 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 |
| BRPI0816382A2 (pt) | 2007-09-06 | 2015-02-24 | Merck Sharp & Dohme | Composto, composição, e, métodos para ativar a guanilato ciclase solúvel e para tratar ou previnir doenças |
| JP2011510082A (ja) | 2008-01-24 | 2011-03-31 | メルク・シャープ・エンド・ドーム・コーポレイション | アンジオテンシンｉｉ受容体拮抗薬 |
| JP2011529073A (ja) | 2008-07-24 | 2011-12-01 | ブリストル−マイヤーズ スクイブ カンパニー | キナーゼ調節因子として有用な縮合ヘテロ環化合物 |
| AU2009299091A1 (en) * | 2008-10-02 | 2010-04-08 | Merck Frosst Canada Ltd. | Heteroaromatic compounds as inhibitors of stearoyl-coenzyme A delta-9 desaturase |
| AU2009322836B2 (en) | 2008-11-25 | 2013-04-04 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| AU2010218224B2 (en) | 2009-02-26 | 2013-06-27 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| EP2531187B1 (en) | 2010-02-05 | 2015-08-12 | Adverio Pharma GmbH | sGC STIMULATORS OR sGC ACTIVATORS ALONE AND IN COMBINATION WITH PDE5 INHBITORS FOR THE TREATMENT OF CYSTIC FIBROSIS |
| US20130178475A1 (en) * | 2010-03-17 | 2013-07-11 | Ironwood Pharmaceuticals, Inc. | sGC STIMULATORS |
| US9284301B2 (en) | 2010-03-25 | 2016-03-15 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| EA023254B1 (ru) | 2010-05-27 | 2016-05-31 | Мерк Шарп Энд Домэ Корп. | Активаторы растворимой гуанилатциклазы |
| WO2011156245A2 (en) * | 2010-06-09 | 2011-12-15 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of mglur2 |
| CN103313976B (zh) * | 2010-06-30 | 2016-11-23 | 铁木医药有限公司 | sGC刺激物 |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| EP2632551B1 (en) | 2010-10-28 | 2016-07-06 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| EP2637659B1 (en) * | 2010-11-09 | 2016-05-18 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| KR101719556B1 (ko) | 2011-03-30 | 2017-03-24 | 주식회사 레고켐 바이오사이언스 | 신규한 세파로스포린 유도체 및 이를 함유하는 의약 조성물 |
| EA026701B1 (ru) | 2011-09-02 | 2017-05-31 | Байер Интеллектуэль Проперти Гмбх | Замещенные аннелированные пиримидины, способ их получения, их применение и лекарственное средство для лечения и/или профилактики заболеваний |
| EP2797915B1 (en) | 2011-12-27 | 2016-07-13 | Ironwood Pharmaceuticals, Inc. | 2-benzyl-3-(oxazole/thiazole)-5-(pyrimidin-2-yl)-1(H)-pyrazole derivatives as stimulators of the soluble guanylate cyclase (sGC) for the treatment of e.g. hypertension or heart failure |
| DE102012200352A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
| ES2644781T3 (es) | 2012-03-06 | 2017-11-30 | Bayer Intellectual Property Gmbh | Azabiciclos sustituidos y su uso |
| 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 |
| WO2014060112A1 (en) * | 2012-10-19 | 2014-04-24 | Origenis Gmbh | Pyrazolo[4,3-d]pyrimidines as kinase inhibitors |
| JP2016505000A (ja) | 2012-12-21 | 2016-02-18 | エピザイム，インコーポレイティド | Ｐｒｍｔ５阻害剤およびその使用 |
| EP2970243B1 (en) * | 2013-03-15 | 2019-11-27 | Cyclerion Therapeutics, Inc. | Sgc stimulators |
| CN114404588A (zh) * | 2013-08-09 | 2022-04-29 | 阿德利克斯公司 | 用于抑制磷酸盐转运的化合物和方法 |
| EP3092231B1 (en) | 2013-12-11 | 2018-06-27 | Ironwood Pharmaceuticals, Inc. | Sgc stimulators |
| US20160324856A1 (en) * | 2014-01-13 | 2016-11-10 | Ironwood Pharmaceuticals, Inc. | Use of sgc stimulators for the treatment of neuromuscular disorders |
| US10047095B2 (en) * | 2014-09-17 | 2018-08-14 | Ironwood Pharmaceuticals, Inc. | sGC stimulators |
| WO2016044447A1 (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 |
| CA3006764A1 (en) * | 2015-12-14 | 2017-06-22 | Ironwood Pharmaceuticals, Inc. | Use of sgc stimulators for the treatment of gastrointestinal sphincter dysfunction |
| IL260701B (en) * | 2016-02-01 | 2022-09-01 | Ironwood Pharmaceuticals Inc | Use of certain sgc stimulators and salts thereof in the preparation of medicaments for the treatment of nonalcoholic steatohepatitis (nash) |
| CR20220309A (es) * | 2016-09-02 | 2022-09-16 | Cyclerion Therapeutics Inc | Estimuladores de sgc |
| US20190381039A1 (en) * | 2016-12-13 | 2019-12-19 | Cyclerion Therapeutics, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS |
-
2015
- 2015-09-16 EP EP15778428.1A patent/EP3194386A2/en not_active Withdrawn
- 2015-09-16 AU AU2015317823A patent/AU2015317823A1/en not_active Abandoned
- 2015-09-16 CN CN201580062197.4A patent/CN107406421A/zh active Pending
- 2015-09-16 CA CA2961489A patent/CA2961489A1/en not_active Abandoned
- 2015-09-16 JP JP2017515197A patent/JP2017527604A/ja not_active Withdrawn
- 2015-09-16 US US15/511,888 patent/US10844064B2/en not_active Expired - Fee Related
- 2015-09-16 WO PCT/US2015/050467 patent/WO2016044446A2/en not_active Ceased
- 2015-09-16 MX MX2017003518A patent/MX2017003518A/es unknown
-
2017
- 2017-03-13 IL IL251113A patent/IL251113A0/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021515018A (ja) * | 2018-03-07 | 2021-06-17 | サイクレリオン・セラピューティクス，インコーポレーテッド | 可溶性グアニル酸シクラーゼ刺激薬を調製するための方法 |
| JP7406692B2 (ja) | 2018-03-07 | 2023-12-28 | ティセント セラピューティクス インコーポレーテッド | 可溶性グアニル酸シクラーゼ刺激薬を調製するための方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016044446A2 (en) | 2016-03-24 |
| EP3194386A2 (en) | 2017-07-26 |
| CA2961489A1 (en) | 2016-03-24 |
| MX2017003518A (es) | 2017-07-28 |
| US10844064B2 (en) | 2020-11-24 |
| AU2015317823A1 (en) | 2017-03-23 |
| IL251113A0 (en) | 2017-04-30 |
| CN107406421A (zh) | 2017-11-28 |
| WO2016044446A3 (en) | 2016-06-16 |
| US20180155345A1 (en) | 2018-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10844064B2 (en) | sGC stimulators | |
| TWI750218B (zh) | sGC 刺激劑 | |
| JP6624616B2 (ja) | ｓＧＣ刺激剤 | |
| EP3092231B1 (en) | Sgc stimulators | |
| US10047095B2 (en) | sGC stimulators | |
| JP7199364B2 (ja) | ｓＧＣ刺激剤 | |
| US11897887B2 (en) | sGC stimulators | |
| US20170298055A1 (en) | sGC STIMULATORS | |
| HK1225030B (en) | Sgc stimulators | |
| HK1225030A1 (en) | Sgc stimulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20180914 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180914 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20190613 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190613 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20190613 |