NZ573307A - 2-0'-methyladen0sine derivatives and their use as agonists or antagonists of an adenosine receptor - Google Patents

Info

Publication number

NZ573307A

NZ573307A NZ573307A NZ57330707A NZ573307A NZ 573307 A NZ573307 A NZ 573307A NZ 573307 A NZ573307 A NZ 573307A NZ 57330707 A NZ57330707 A NZ 57330707A NZ 573307 A NZ573307 A NZ 573307A

Authority

NZ

New Zealand

Prior art keywords

pain

amino

purin

methoxytetrahydrofuran

hydroxymethyl

Prior art date

2006-06-27

Links

• Espacenet
• Global Dossier
• Discuss

• 108050000203 Adenosine receptors Proteins 0.000 title description 39
• 102000009346 Adenosine receptors Human genes 0.000 title description 38
• 239000000556 agonist Substances 0.000 title description 9
• 239000005557 antagonist Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 101
• 208000002193 Pain Diseases 0.000 claims abstract description 49
• 230000036407 pain Effects 0.000 claims abstract description 48
• 206010061218 Inflammation Diseases 0.000 claims abstract description 26
• 230000004054 inflammatory process Effects 0.000 claims abstract description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
• 230000000694 effects Effects 0.000 claims description 59
• 239000003814 drug Substances 0.000 claims description 47
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 33
• 238000000034 method Methods 0.000 claims description 29
• -1 2,2,3,3-tetrafluorocyclobutyl Chemical group 0.000 claims description 26
• 230000001575 pathological effect Effects 0.000 claims description 24
• 239000003435 antirheumatic agent Substances 0.000 claims description 22
• 206010012601 diabetes mellitus Diseases 0.000 claims description 22
• 230000002265 prevention Effects 0.000 claims description 22
• 208000004454 Hyperalgesia Diseases 0.000 claims description 21
• 230000006378 damage Effects 0.000 claims description 21
• 208000028867 ischemia Diseases 0.000 claims description 16
• 210000001519 tissue Anatomy 0.000 claims description 16
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 102000007471 Adenosine A2A receptor Human genes 0.000 claims description 12
• 108010085277 Adenosine A2A receptor Proteins 0.000 claims description 12
• 206010028980 Neoplasm Diseases 0.000 claims description 12
• 230000008484 agonism Effects 0.000 claims description 12
• 208000036487 Arthropathies Diseases 0.000 claims description 11
• 201000001320 Atherosclerosis Diseases 0.000 claims description 11
• 208000035154 Hyperesthesia Diseases 0.000 claims description 11
• 208000012659 Joint disease Diseases 0.000 claims description 11
• 230000003110 anti-inflammatory effect Effects 0.000 claims description 11
• 230000002757 inflammatory effect Effects 0.000 claims description 11
• 201000011510 cancer Diseases 0.000 claims description 10
• 230000000302 ischemic effect Effects 0.000 claims description 10
• 201000008482 osteoarthritis Diseases 0.000 claims description 10
• 239000000047 product Substances 0.000 claims description 10
• 206010063837 Reperfusion injury Diseases 0.000 claims description 9
• 208000036142 Viral infection Diseases 0.000 claims description 9
• 230000002411 adverse Effects 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 230000009385 viral infection Effects 0.000 claims description 9
• 206010001513 AIDS related complex Diseases 0.000 claims description 8
• 206010002383 Angina Pectoris Diseases 0.000 claims description 8
• 201000005569 Gout Diseases 0.000 claims description 8
• 201000006417 multiple sclerosis Diseases 0.000 claims description 8
• 208000004296 neuralgia Diseases 0.000 claims description 8
• 208000021722 neuropathic pain Diseases 0.000 claims description 8
• 208000035143 Bacterial infection Diseases 0.000 claims description 7
• 206010003246 arthritis Diseases 0.000 claims description 7
• 230000001580 bacterial effect Effects 0.000 claims description 7
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 7
• 210000004027 cell Anatomy 0.000 claims description 7
• 210000004072 lung Anatomy 0.000 claims description 7
• 230000002981 neuropathic effect Effects 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 208000011580 syndromic disease Diseases 0.000 claims description 7
• 230000000451 tissue damage Effects 0.000 claims description 7
• 231100000827 tissue damage Toxicity 0.000 claims description 7
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
• 206010006895 Cachexia Diseases 0.000 claims description 6
• 206010063094 Cerebral malaria Diseases 0.000 claims description 6
• 206010020751 Hypersensitivity Diseases 0.000 claims description 6
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 6
• 208000006011 Stroke Diseases 0.000 claims description 6
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 6
• 230000001363 autoimmune Effects 0.000 claims description 6
• 206010006451 bronchitis Diseases 0.000 claims description 6
• 230000001684 chronic effect Effects 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 6
• 208000015181 infectious disease Diseases 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 230000029663 wound healing Effects 0.000 claims description 6
• 206010061666 Autonomic neuropathy Diseases 0.000 claims description 5
• 208000008035 Back Pain Diseases 0.000 claims description 5
• 208000001640 Fibromyalgia Diseases 0.000 claims description 5
• 206010018634 Gouty Arthritis Diseases 0.000 claims description 5
• 208000004550 Postoperative Pain Diseases 0.000 claims description 5
• 208000017442 Retinal disease Diseases 0.000 claims description 5
• 206010038923 Retinopathy Diseases 0.000 claims description 5
• 206010040070 Septic Shock Diseases 0.000 claims description 5
• 210000004204 blood vessel Anatomy 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• 208000017169 kidney disease Diseases 0.000 claims description 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
• 229940124597 therapeutic agent Drugs 0.000 claims description 5
• 230000002792 vascular Effects 0.000 claims description 5
• 208000030507 AIDS Diseases 0.000 claims description 4
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 4
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
• 206010058019 Cancer Pain Diseases 0.000 claims description 4
• 206010007558 Cardiac failure chronic Diseases 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
• 102000008186 Collagen Human genes 0.000 claims description 4
• 108010035532 Collagen Proteins 0.000 claims description 4
• 201000004624 Dermatitis Diseases 0.000 claims description 4
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
• 201000009273 Endometriosis Diseases 0.000 claims description 4
• 206010019280 Heart failures Diseases 0.000 claims description 4
• 208000007514 Herpes zoster Diseases 0.000 claims description 4
• 208000032571 Infant acute respiratory distress syndrome Diseases 0.000 claims description 4
• 206010022562 Intermittent claudication Diseases 0.000 claims description 4
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
• 206010027202 Meningitis bacterial Diseases 0.000 claims description 4
• 208000007101 Muscle Cramp Diseases 0.000 claims description 4
• 208000000112 Myalgia Diseases 0.000 claims description 4
• 206010028974 Neonatal respiratory distress syndrome Diseases 0.000 claims description 4
• 208000008589 Obesity Diseases 0.000 claims description 4
• 208000001132 Osteoporosis Diseases 0.000 claims description 4
• 208000000450 Pelvic Pain Diseases 0.000 claims description 4
• 206010035664 Pneumonia Diseases 0.000 claims description 4
• 206010037660 Pyrexia Diseases 0.000 claims description 4
• 206010049771 Shock haemorrhagic Diseases 0.000 claims description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
• 206010047163 Vasospasm Diseases 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 206010069351 acute lung injury Diseases 0.000 claims description 4
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
• 208000026935 allergic disease Diseases 0.000 claims description 4
• 230000007815 allergy Effects 0.000 claims description 4
• 206010003119 arrhythmia Diseases 0.000 claims description 4
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 201000009904 bacterial meningitis Diseases 0.000 claims description 4
• 229920001436 collagen Polymers 0.000 claims description 4
• 230000005764 inhibitory process Effects 0.000 claims description 4
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
• 208000011379 keloid formation Diseases 0.000 claims description 4
• 210000004185 liver Anatomy 0.000 claims description 4
• 201000005202 lung cancer Diseases 0.000 claims description 4
• 208000020816 lung neoplasm Diseases 0.000 claims description 4
• 230000036210 malignancy Effects 0.000 claims description 4
• 206010028417 myasthenia gravis Diseases 0.000 claims description 4
• 201000002652 newborn respiratory distress syndrome Diseases 0.000 claims description 4
• 235000020824 obesity Nutrition 0.000 claims description 4
• 210000000056 organ Anatomy 0.000 claims description 4
• 208000008423 pleurisy Diseases 0.000 claims description 4
• 230000002685 pulmonary effect Effects 0.000 claims description 4
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
• 230000008695 pulmonary vasoconstriction Effects 0.000 claims description 4
• 230000029058 respiratory gaseous exchange Effects 0.000 claims description 4
• 231100000241 scar Toxicity 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 230000009772 tissue formation Effects 0.000 claims description 4
• 208000019553 vascular disease Diseases 0.000 claims description 4
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
• 208000006820 Arthralgia Diseases 0.000 claims description 3
• 206010006811 Bursitis Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 208000008930 Low Back Pain Diseases 0.000 claims description 3
• 206010050219 Lumbar radiculopathy Diseases 0.000 claims description 3
• 206010036105 Polyneuropathy Diseases 0.000 claims description 3
• 206010039203 Road traffic accident Diseases 0.000 claims description 3
• 208000008765 Sciatica Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 208000000491 Tendinopathy Diseases 0.000 claims description 3
• 206010043255 Tendonitis Diseases 0.000 claims description 3
• 208000026816 acute arthritis Diseases 0.000 claims description 3
• 208000019664 bone resorption disease Diseases 0.000 claims description 3
• 230000000747 cardiac effect Effects 0.000 claims description 3
• 208000029078 coronary artery disease Diseases 0.000 claims description 3
• 208000035475 disorder Diseases 0.000 claims description 3
• 206010015037 epilepsy Diseases 0.000 claims description 3
• 208000014674 injury Diseases 0.000 claims description 3
• 210000002540 macrophage Anatomy 0.000 claims description 3
• 201000001119 neuropathy Diseases 0.000 claims description 3
• 230000007823 neuropathy Effects 0.000 claims description 3
• 230000010412 perfusion Effects 0.000 claims description 3
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
• 230000007824 polyneuropathy Effects 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 238000001356 surgical procedure Methods 0.000 claims description 3
• 201000004415 tendinitis Diseases 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• 206010000087 Abdominal pain upper Diseases 0.000 claims description 2
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 2
• 206010002329 Aneurysm Diseases 0.000 claims description 2
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
• 208000023275 Autoimmune disease Diseases 0.000 claims description 2
• 208000000003 Breakthrough pain Diseases 0.000 claims description 2
• 206010006187 Breast cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
• 206010006482 Bronchospasm Diseases 0.000 claims description 2
• 201000009030 Carcinoma Diseases 0.000 claims description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
• 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
• 206010008479 Chest Pain Diseases 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
• 206010051055 Deep vein thrombosis Diseases 0.000 claims description 2
• 206010012442 Dermatitis contact Diseases 0.000 claims description 2
• 206010052337 Diastolic dysfunction Diseases 0.000 claims description 2
• 206010014561 Emphysema Diseases 0.000 claims description 2
• 208000007530 Essential hypertension Diseases 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 2
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 2
• 206010018691 Granuloma Diseases 0.000 claims description 2
• 208000031886 HIV Infections Diseases 0.000 claims description 2
• 208000037357 HIV infectious disease Diseases 0.000 claims description 2
• 206010019027 Haemothorax Diseases 0.000 claims description 2
• 206010058179 Hypertensive emergency Diseases 0.000 claims description 2
• 208000004575 Infectious Arthritis Diseases 0.000 claims description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
• 108010002350 Interleukin-2 Proteins 0.000 claims description 2
• 208000029523 Interstitial Lung disease Diseases 0.000 claims description 2
• 206010023125 Jarisch-Herxheimer reaction Diseases 0.000 claims description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
• 208000007914 Labor Pain Diseases 0.000 claims description 2
• 201000008197 Laryngitis Diseases 0.000 claims description 2
• 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims description 2
• 208000019693 Lung disease Diseases 0.000 claims description 2
• 206010025323 Lymphomas Diseases 0.000 claims description 2
• 206010027476 Metastases Diseases 0.000 claims description 2
• 206010028116 Mucosal inflammation Diseases 0.000 claims description 2
• 201000010927 Mucositis Diseases 0.000 claims description 2
• 208000030858 Myofascial Pain Syndromes Diseases 0.000 claims description 2
• 206010028735 Nasal congestion Diseases 0.000 claims description 2
• 206010028836 Neck pain Diseases 0.000 claims description 2
• 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 claims description 2
• 206010029888 Obliterative bronchiolitis Diseases 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• 206010033645 Pancreatitis Diseases 0.000 claims description 2
• 206010033647 Pancreatitis acute Diseases 0.000 claims description 2
• 206010061339 Perineal pain Diseases 0.000 claims description 2
• 208000004983 Phantom Limb Diseases 0.000 claims description 2
• 206010056238 Phantom pain Diseases 0.000 claims description 2
• 208000002151 Pleural effusion Diseases 0.000 claims description 2
• 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
• 206010037423 Pulmonary oedema Diseases 0.000 claims description 2
• 206010038389 Renal cancer Diseases 0.000 claims description 2
• 206010038563 Reocclusion Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 206010048908 Seasonal allergy Diseases 0.000 claims description 2
• 201000010001 Silicosis Diseases 0.000 claims description 2
• 208000007718 Stable Angina Diseases 0.000 claims description 2
• 208000005279 Status Asthmaticus Diseases 0.000 claims description 2
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 2
• 206010071436 Systolic dysfunction Diseases 0.000 claims description 2
• 208000028911 Temporomandibular Joint disease Diseases 0.000 claims description 2
• 206010043220 Temporomandibular joint syndrome Diseases 0.000 claims description 2
• 208000001435 Thromboembolism Diseases 0.000 claims description 2
• 206010044248 Toxic shock syndrome Diseases 0.000 claims description 2
• 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 2
• 206010052779 Transplant rejections Diseases 0.000 claims description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
• 208000025865 Ulcer Diseases 0.000 claims description 2
• 206010047115 Vasculitis Diseases 0.000 claims description 2
• 206010047249 Venous thrombosis Diseases 0.000 claims description 2
• 208000024716 acute asthma Diseases 0.000 claims description 2
• 201000003229 acute pancreatitis Diseases 0.000 claims description 2
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 2
• 229960003942 amphotericin b Drugs 0.000 claims description 2
• 238000002399 angioplasty Methods 0.000 claims description 2
• 230000006793 arrhythmia Effects 0.000 claims description 2
• 206010003230 arteritis Diseases 0.000 claims description 2
• 230000002917 arthritic effect Effects 0.000 claims description 2
• 208000010668 atopic eczema Diseases 0.000 claims description 2
• 230000017531 blood circulation Effects 0.000 claims description 2
• 210000000988 bone and bone Anatomy 0.000 claims description 2
• 210000000481 breast Anatomy 0.000 claims description 2
• 201000009267 bronchiectasis Diseases 0.000 claims description 2
• 201000003848 bronchiolitis obliterans Diseases 0.000 claims description 2
• 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims description 2
• 230000007885 bronchoconstriction Effects 0.000 claims description 2
• 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
• 239000007795 chemical reaction product Substances 0.000 claims description 2
• 208000023819 chronic asthma Diseases 0.000 claims description 2
• 208000007451 chronic bronchitis Diseases 0.000 claims description 2
• 208000024980 claudication Diseases 0.000 claims description 2
• 208000029742 colonic neoplasm Diseases 0.000 claims description 2
• 208000010247 contact dermatitis Diseases 0.000 claims description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 230000007812 deficiency Effects 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 206010014599 encephalitis Diseases 0.000 claims description 2
• 210000003979 eosinophil Anatomy 0.000 claims description 2
• 230000004761 fibrosis Effects 0.000 claims description 2
• 230000002008 hemorrhagic effect Effects 0.000 claims description 2
• 230000002440 hepatic effect Effects 0.000 claims description 2
• 208000006454 hepatitis Diseases 0.000 claims description 2
• 231100000283 hepatitis Toxicity 0.000 claims description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
• 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
• 230000009610 hypersensitivity Effects 0.000 claims description 2
• 208000000509 infertility Diseases 0.000 claims description 2
• 230000036512 infertility Effects 0.000 claims description 2
• 231100000535 infertility Toxicity 0.000 claims description 2
• 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
• 239000002085 irritant Substances 0.000 claims description 2
• 231100000021 irritant Toxicity 0.000 claims description 2
• 201000010982 kidney cancer Diseases 0.000 claims description 2
• 208000032839 leukemia Diseases 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 201000005857 malignant hypertension Diseases 0.000 claims description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 235000013336 milk Nutrition 0.000 claims description 2
• 239000008267 milk Substances 0.000 claims description 2
• 210000004080 milk Anatomy 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
• 210000000440 neutrophil Anatomy 0.000 claims description 2
• 201000002528 pancreatic cancer Diseases 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 208000008494 pericarditis Diseases 0.000 claims description 2
• 208000030613 peripheral artery disease Diseases 0.000 claims description 2
• 230000002085 persistent effect Effects 0.000 claims description 2
• 206010035653 pneumoconiosis Diseases 0.000 claims description 2
• 201000003144 pneumothorax Diseases 0.000 claims description 2
• 210000002307 prostate Anatomy 0.000 claims description 2
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
• 230000010410 reperfusion Effects 0.000 claims description 2
• 230000010076 replication Effects 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 201000000306 sarcoidosis Diseases 0.000 claims description 2
• 201000001223 septic arthritis Diseases 0.000 claims description 2
• 230000036303 septic shock Effects 0.000 claims description 2
• 201000009890 sinusitis Diseases 0.000 claims description 2
• 210000003491 skin Anatomy 0.000 claims description 2
• 230000000391 smoking effect Effects 0.000 claims description 2
• 208000020431 spinal cord injury Diseases 0.000 claims description 2
• 208000005198 spinal stenosis Diseases 0.000 claims description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
• 239000002753 trypsin inhibitor Substances 0.000 claims description 2
• 231100000397 ulcer Toxicity 0.000 claims description 2
• 208000001319 vasomotor rhinitis Diseases 0.000 claims description 2
• 201000005539 vernal conjunctivitis Diseases 0.000 claims description 2
• 230000000052 comparative effect Effects 0.000 claims 5
• WJAOJLDJPQVXEX-UHFFFAOYSA-N 2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound COC1COC(CO)C1O WJAOJLDJPQVXEX-UHFFFAOYSA-N 0.000 claims 2
• 201000002661 Spondylitis Diseases 0.000 claims 2
• 208000024827 Alzheimer disease Diseases 0.000 claims 1
• 206010014824 Endotoxic shock Diseases 0.000 claims 1
• 102100020873 Interleukin-2 Human genes 0.000 claims 1
• 208000016604 Lyme disease Diseases 0.000 claims 1
• 241001256820 Phalangitis Species 0.000 claims 1
• 101150046432 Tril gene Proteins 0.000 claims 1
• 238000010438 heat treatment Methods 0.000 claims 1
• 210000003205 muscle Anatomy 0.000 claims 1
• PDXZVRUKHZDJHA-MDSCUQPFSA-N (2r,3r,4r,5r)-5-[6-amino-2-(2,2,3,3-tetrafluorocyclobutyl)oxypurin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(OC3C(C(F)(F)C3)(F)F)=NC(N)=C2N=C1 PDXZVRUKHZDJHA-MDSCUQPFSA-N 0.000 abstract description 2
• ZVAGZDJXBUJVJN-XNIJJKJLSA-N (2r,3r,4r,5r)-5-[6-amino-2-(cyclopentylmethoxy)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(OCC3CCCC3)=NC(N)=C2N=C1 ZVAGZDJXBUJVJN-XNIJJKJLSA-N 0.000 abstract description 2
• JYOWRDDMYCFMOZ-XNIJJKJLSA-N (2r,3r,4r,5r)-5-[6-amino-2-(3,4-difluorophenoxy)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(OC=3C=C(F)C(F)=CC=3)=NC(N)=C2N=C1 JYOWRDDMYCFMOZ-XNIJJKJLSA-N 0.000 abstract 1
• YPRAZLHFKHILSL-XNIJJKJLSA-N (2r,3r,4r,5r)-5-[6-amino-2-(cyclohexylamino)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(NC3CCCCC3)=NC(N)=C2N=C1 YPRAZLHFKHILSL-XNIJJKJLSA-N 0.000 abstract 1
• PVWCNEQLUBRLFH-XNIJJKJLSA-N (2r,3r,4r,5r)-5-[6-amino-2-[4-chloro-3-(trifluoromethyl)phenoxy]purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(OC=3C=C(C(Cl)=CC=3)C(F)(F)F)=NC(N)=C2N=C1 PVWCNEQLUBRLFH-XNIJJKJLSA-N 0.000 abstract 1
• 229940002612 prodrug Drugs 0.000 description 96
• 239000000651 prodrug Substances 0.000 description 96
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 79
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
• 239000002207 metabolite Substances 0.000 description 59
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 47
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
• 238000001727 in vivo Methods 0.000 description 38
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• 102000005962 receptors Human genes 0.000 description 32
• 108020003175 receptors Proteins 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 28
• 239000002988 disease modifying antirheumatic drug Substances 0.000 description 26
• 230000036470 plasma concentration Effects 0.000 description 26
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 24
• 229960005305 adenosine Drugs 0.000 description 24
• AJACDNCVEGIBNA-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(6-amino-2-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C12=NC(OC)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O AJACDNCVEGIBNA-KQYNXXCUSA-N 0.000 description 23
• AJACDNCVEGIBNA-UHFFFAOYSA-N 2-Methoxyadenosine Natural products C12=NC(OC)=NC(N)=C2N=CN1C1OC(CO)C(O)C1O AJACDNCVEGIBNA-UHFFFAOYSA-N 0.000 description 23
• 239000000243 solution Substances 0.000 description 23
• 239000012071 phase Substances 0.000 description 22
• 239000002904 solvent Substances 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
• 229940079593 drug Drugs 0.000 description 19
• 239000000203 mixture Substances 0.000 description 19
• 150000003839 salts Chemical class 0.000 description 19
• 230000014759 maintenance of location Effects 0.000 description 18
• 239000003379 purinergic P1 receptor agonist Substances 0.000 description 17
• 239000002253 acid Substances 0.000 description 13
• 238000004128 high performance liquid chromatography Methods 0.000 description 13
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
• 238000002360 preparation method Methods 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 101150051188 Adora2a gene Proteins 0.000 description 11
• 241001465754 Metazoa Species 0.000 description 11
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 11
• 230000002441 reversible effect Effects 0.000 description 11
• 239000007787 solid Substances 0.000 description 11
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 11
• 206010053552 allodynia Diseases 0.000 description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
• 239000013543 active substance Substances 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 229960001052 streptozocin Drugs 0.000 description 9
• 241000700159 Rattus Species 0.000 description 8
• 229940035676 analgesics Drugs 0.000 description 8
• 239000000730 antalgic agent Substances 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• 239000002777 nucleoside Substances 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
• 208000001953 Hypotension Diseases 0.000 description 7
• 229960004150 aciclovir Drugs 0.000 description 7
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 210000001503 joint Anatomy 0.000 description 7
• 150000003833 nucleoside derivatives Chemical class 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 230000003068 static effect Effects 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 208000001871 Tachycardia Diseases 0.000 description 6
• 240000007591 Tilia tomentosa Species 0.000 description 6
• 230000000202 analgesic effect Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 230000036543 hypotension Effects 0.000 description 6
• 230000003389 potentiating effect Effects 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 229940123907 Disease modifying antirheumatic drug Drugs 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 150000003835 adenosine derivatives Chemical class 0.000 description 5
• 230000003070 anti-hyperalgesia Effects 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 230000036772 blood pressure Effects 0.000 description 5
• 125000000623 heterocyclic group Chemical group 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 230000037324 pain perception Effects 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 239000000018 receptor agonist Substances 0.000 description 5
• 229940044601 receptor agonist Drugs 0.000 description 5
• 230000006794 tachycardia Effects 0.000 description 5
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
• 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 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 241000282326 Felis catus Species 0.000 description 4
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
• HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 208000006218 bradycardia Diseases 0.000 description 4
• 230000036471 bradycardia Effects 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
• 229940127240 opiate Drugs 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 238000002953 preparative HPLC Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 230000001953 sensory effect Effects 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 229940093257 valacyclovir Drugs 0.000 description 4
• COJBZAYNQJNHGF-OFBQIVOGSA-N (2r,3s,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methoxyoxolane-3,4-diol Chemical compound CO[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 COJBZAYNQJNHGF-OFBQIVOGSA-N 0.000 description 3
• FPUGCISOLXNPPC-IOSLPCCCSA-N 2'-methoxyadenosine Natural products CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-IOSLPCCCSA-N 0.000 description 3
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 102000055025 Adenosine deaminases Human genes 0.000 description 3
• PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• 206010065390 Inflammatory pain Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 229940024606 amino acid Drugs 0.000 description 3
• 230000008485 antagonism Effects 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
• 230000000916 dilatatory effect Effects 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 210000004209 hair Anatomy 0.000 description 3
• 229910052736 halogen Inorganic materials 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 210000005036 nerve Anatomy 0.000 description 3
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 210000001044 sensory neuron Anatomy 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• SRPWOOOHEPICQU-UHFFFAOYSA-N trimellitic anhydride Chemical compound OC(=O)C1=CC=C2C(=O)OC(=O)C2=C1 SRPWOOOHEPICQU-UHFFFAOYSA-N 0.000 description 3
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 3
• 229960002555 zidovudine Drugs 0.000 description 3
• SRWUHMQKNPGXOP-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[6-amino-2-[2-(4-methylphenyl)ethoxy]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=CC(C)=CC=C1CCOC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 SRWUHMQKNPGXOP-SCFUHWHPSA-N 0.000 description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
• HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
• ZDTFMPXQUSBYRL-UUOKFMHZSA-N 2-Aminoadenosine Chemical class C12=NC(N)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZDTFMPXQUSBYRL-UUOKFMHZSA-N 0.000 description 2
• 101150046889 ADORA3 gene Proteins 0.000 description 2
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
• 229930024421 Adenine Natural products 0.000 description 2
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 206010021143 Hypoxia Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000906034 Orthops Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 229960000643 adenine Drugs 0.000 description 2
• 150000003838 adenosines Chemical class 0.000 description 2
• 125000000217 alkyl group Chemical group 0.000 description 2
• 230000001668 ameliorated effect Effects 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000003574 anti-allodynic effect Effects 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
• 230000000975 bioactive effect Effects 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 230000036770 blood supply Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 239000003557 cannabinoid Substances 0.000 description 2
• 229930003827 cannabinoid Natural products 0.000 description 2
• 229940065144 cannabinoids Drugs 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 229920001525 carrageenan Polymers 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 229960004275 glycolic acid Drugs 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 229940048921 humira Drugs 0.000 description 2
• 230000000917 hyperalgesic effect Effects 0.000 description 2
• 230000002631 hypothermal effect Effects 0.000 description 2
• 230000007954 hypoxia Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 238000011813 knockout mouse model Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 231100000682 maximum tolerated dose Toxicity 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 210000000653 nervous system Anatomy 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 229940127073 nucleoside analogue Drugs 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 108010082406 peptide permease Proteins 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 229960000329 ribavirin Drugs 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000012266 salt solution Substances 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229940083542 sodium Drugs 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 2
• 229950006081 taribavirin Drugs 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 230000000304 vasodilatating effect Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
• MGEBVSZZNFOIRB-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(6-amino-2-iodopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(I)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O MGEBVSZZNFOIRB-UUOKFMHZSA-N 0.000 description 1
• HSCDJYUJIKPWKV-IDTAVKCVSA-N (2r,3r,4s,5r)-2-(6-amino-2-pentoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C12=NC(OCCCCC)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HSCDJYUJIKPWKV-IDTAVKCVSA-N 0.000 description 1
• GCHOQLCPANZXCE-SDBHATRESA-N (2r,3r,4s,5r)-2-(6-amino-2-phenoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1OC1=CC=CC=C1 GCHOQLCPANZXCE-SDBHATRESA-N 0.000 description 1
• LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 description 1
• FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical compound C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 description 1
• IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 1
• VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• AYTPIVIDHMVGSX-UHFFFAOYSA-N 2,1,3-benzoselenadiazole Chemical compound C1=CC=CC2=N[se]N=C21 AYTPIVIDHMVGSX-UHFFFAOYSA-N 0.000 description 1
• AWBOSXFRPFZLOP-UHFFFAOYSA-N 2,1,3-benzoxadiazole Chemical compound C1=CC=CC2=NON=C21 AWBOSXFRPFZLOP-UHFFFAOYSA-N 0.000 description 1
• FNENUTDUAXPVTF-UHFFFAOYSA-N 2,2,3,3-tetrafluorocyclobutan-1-ol Chemical compound OC1CC(F)(F)C1(F)F FNENUTDUAXPVTF-UHFFFAOYSA-N 0.000 description 1
• VOGSDFLJZPNWHY-UHFFFAOYSA-N 2,2-difluoroethanol Chemical compound OCC(F)F VOGSDFLJZPNWHY-UHFFFAOYSA-N 0.000 description 1
• INXKVYFOWNAVMU-UHFFFAOYSA-N 2,5-difluorophenol Chemical compound OC1=CC(F)=CC=C1F INXKVYFOWNAVMU-UHFFFAOYSA-N 0.000 description 1
• KUCWUAFNGCMZDB-UHFFFAOYSA-N 2-amino-3-nitrophenol Chemical compound NC1=C(O)C=CC=C1[N+]([O-])=O KUCWUAFNGCMZDB-UHFFFAOYSA-N 0.000 description 1
• UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
• HKCXKNGHGLCFHK-UHFFFAOYSA-N 2-methoxy-7h-purine Chemical compound COC1=NC=C2NC=NC2=N1 HKCXKNGHGLCFHK-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• BNPWVUJOPCGHIK-UHFFFAOYSA-N 3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1 BNPWVUJOPCGHIK-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• ZLFPIEUWXNRPNM-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)phenol Chemical compound OC1=CC=C(Cl)C(C(F)(F)F)=C1 ZLFPIEUWXNRPNM-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
• 239000005964 Acibenzolar-S-methyl Substances 0.000 description 1
• 101150078577 Adora2b gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 101800004538 Bradykinin Proteins 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 108010074051 C-Reactive Protein Proteins 0.000 description 1
• 102100032752 C-reactive protein Human genes 0.000 description 1
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
• 108090000312 Calcium Channels Proteins 0.000 description 1
• 102000003922 Calcium Channels Human genes 0.000 description 1
• 206010007710 Cartilage injury Diseases 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 206010008089 Cerebral artery occlusion Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000000094 Chronic Pain Diseases 0.000 description 1
• 208000006154 Chronic hepatitis C Diseases 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 206010011086 Coronary artery occlusion Diseases 0.000 description 1
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 206010049119 Emotional distress Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
• 208000010496 Heart Arrest Diseases 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010021113 Hypothermia Diseases 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 102000000588 Interleukin-2 Human genes 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 206010023232 Joint swelling Diseases 0.000 description 1
• 102100035792 Kininogen-1 Human genes 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 238000000585 Mann–Whitney U test Methods 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 206010049565 Muscle fatigue Diseases 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• 208000001294 Nociceptive Pain Diseases 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000001431 Psychomotor Agitation Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 206010048988 Renal artery occlusion Diseases 0.000 description 1
• 102100028255 Renin Human genes 0.000 description 1
• 108090000783 Renin Proteins 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 102000003141 Tachykinin Human genes 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 1
• 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 235000011054 acetic acid Nutrition 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002465 adenosine A2a receptor agonist Substances 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• 230000003556 anti-epileptic effect Effects 0.000 description 1
• 230000003602 anti-herpes Effects 0.000 description 1
• 230000003276 anti-hypertensive effect Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 229960003965 antiepileptics Drugs 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 229940121357 antivirals Drugs 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 230000001174 ascending effect Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
• 229960005207 auranofin Drugs 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 1
• 239000003855 balanced salt solution Substances 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 238000010170 biological method Methods 0.000 description 1
• 230000036983 biotransformation Effects 0.000 description 1
• 230000008081 blood perfusion Effects 0.000 description 1
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000005779 cell damage Effects 0.000 description 1
• 208000037887 cell injury Diseases 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 229960003677 chloroquine Drugs 0.000 description 1
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 230000001447 compensatory effect Effects 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 229940125833 compound 23 Drugs 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 229940111134 coxibs Drugs 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• FOYWGUOQMYJRRR-UHFFFAOYSA-N dec-4-ene Chemical compound [CH2]CCC=CCCCCC FOYWGUOQMYJRRR-UHFFFAOYSA-N 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 230000036267 drug metabolism Effects 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 235000019439 ethyl acetate Nutrition 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 238000010304 firing Methods 0.000 description 1
• 238000010579 first pass effect Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000003304 gavage Methods 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 229940076085 gold Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 229940029575 guanosine Drugs 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000002837 heart atrium Anatomy 0.000 description 1
• 208000010710 hepatitis C virus infection Diseases 0.000 description 1
• 125000005842 heteroatom 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
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000053391 human F Human genes 0.000 description 1
• 108700031895 human F Proteins 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
• 229960004171 hydroxychloroquine Drugs 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 208000021822 hypotensive Diseases 0.000 description 1
• 230000001077 hypotensive 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
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 230000031891 intestinal absorption Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 210000004153 islets of langerhan Anatomy 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 210000004731 jugular vein Anatomy 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960000448 lactic acid Drugs 0.000 description 1
• 229960001375 lactose Drugs 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229940098895 maleic acid Drugs 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 239000003158 myorelaxant agent Substances 0.000 description 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000003533 narcotic effect Effects 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 230000008035 nerve activity Effects 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 230000003040 nociceptive effect Effects 0.000 description 1
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 108091006527 nucleoside transporters Proteins 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229940124583 pain medication Drugs 0.000 description 1
• 230000008533 pain sensitivity Effects 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 229960005489 paracetamol Drugs 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229960001639 penicillamine Drugs 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 235000020030 perry Nutrition 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000005561 phenanthryl group Chemical group 0.000 description 1
• 125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
• 239000002644 phorbol ester Substances 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 229960001233 pregabalin Drugs 0.000 description 1
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000006920 protein precipitation Effects 0.000 description 1
• 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
• 125000001725 pyrenyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229910052711 selenium Inorganic materials 0.000 description 1
• 239000011669 selenium Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000002553 single reaction monitoring Methods 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 238000012453 sprague-dawley rat model Methods 0.000 description 1
• 238000005507 spraying Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 229940032147 starch Drugs 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 108060008037 tachykinin Proteins 0.000 description 1
• 238000004885 tandem mass spectrometry Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 230000017423 tissue regeneration Effects 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
• 229940045145 uridine Drugs 0.000 description 1
• 230000036325 urinary excretion Effects 0.000 description 1
• 229960004295 valine Drugs 0.000 description 1
• 125000002114 valyl group Chemical group 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
• 239000013598 vector Substances 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1