JP2009541437A - 治療用化合物 - Google Patents
治療用化合物 Download PDFInfo
- Publication number
- JP2009541437A JP2009541437A JP2009517174A JP2009517174A JP2009541437A JP 2009541437 A JP2009541437 A JP 2009541437A JP 2009517174 A JP2009517174 A JP 2009517174A JP 2009517174 A JP2009517174 A JP 2009517174A JP 2009541437 A JP2009541437 A JP 2009541437A
- Authority
- JP
- Japan
- Prior art keywords
- pain
- disease
- adenosine
- cancer
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 93
- 230000001225 therapeutic effect Effects 0.000 title description 7
- 208000002193 Pain Diseases 0.000 claims abstract description 72
- 230000036407 pain Effects 0.000 claims abstract description 71
- 239000003814 drug Substances 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 36
- 206010061218 Inflammation Diseases 0.000 claims abstract description 32
- 230000004054 inflammatory process Effects 0.000 claims abstract description 32
- 239000002988 disease modifying antirheumatic drug Substances 0.000 claims abstract description 26
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 12
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 230000000694 effects Effects 0.000 claims description 51
- 108050000203 Adenosine receptors Proteins 0.000 claims description 40
- 102000009346 Adenosine receptors Human genes 0.000 claims description 39
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 38
- 206010012601 diabetes mellitus Diseases 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 230000001575 pathological effect Effects 0.000 claims description 25
- 208000004454 Hyperalgesia Diseases 0.000 claims description 23
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 22
- -1 cyclopentylmethoxy Chemical group 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 230000002265 prevention Effects 0.000 claims description 18
- 206010003246 arthritis Diseases 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 17
- 230000006378 damage Effects 0.000 claims description 17
- 210000001519 tissue Anatomy 0.000 claims description 16
- 230000001668 ameliorated effect Effects 0.000 claims description 15
- 208000028867 ischemia Diseases 0.000 claims description 15
- 201000008482 osteoarthritis Diseases 0.000 claims description 15
- 208000008035 Back Pain Diseases 0.000 claims description 14
- 230000002757 inflammatory effect Effects 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 208000036487 Arthropathies Diseases 0.000 claims description 13
- 201000001320 Atherosclerosis Diseases 0.000 claims description 13
- 201000005569 Gout Diseases 0.000 claims description 13
- 208000035154 Hyperesthesia Diseases 0.000 claims description 13
- 208000012659 Joint disease Diseases 0.000 claims description 13
- 206010063837 Reperfusion injury Diseases 0.000 claims description 13
- 230000008484 agonism Effects 0.000 claims description 13
- 206010001513 AIDS related complex Diseases 0.000 claims description 12
- 208000036142 Viral infection Diseases 0.000 claims description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 230000009385 viral infection Effects 0.000 claims description 12
- 102000007471 Adenosine A2A receptor Human genes 0.000 claims description 11
- 108010085277 Adenosine A2A receptor Proteins 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 11
- 230000000302 ischemic effect Effects 0.000 claims description 11
- 208000035143 Bacterial infection Diseases 0.000 claims description 10
- 206010020751 Hypersensitivity Diseases 0.000 claims description 10
- 230000001580 bacterial effect Effects 0.000 claims description 10
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 210000004072 lung Anatomy 0.000 claims description 10
- 230000000451 tissue damage Effects 0.000 claims description 10
- 231100000827 tissue damage Toxicity 0.000 claims description 10
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 9
- 206010002383 Angina Pectoris Diseases 0.000 claims description 9
- 206010006895 Cachexia Diseases 0.000 claims description 9
- 206010063094 Cerebral malaria Diseases 0.000 claims description 9
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 9
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 230000001363 autoimmune Effects 0.000 claims description 9
- 206010006451 bronchitis Diseases 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 210000004185 liver Anatomy 0.000 claims description 9
- 208000004296 neuralgia Diseases 0.000 claims description 9
- 208000021722 neuropathic pain Diseases 0.000 claims description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 8
- 208000001640 Fibromyalgia Diseases 0.000 claims description 8
- 208000004550 Postoperative Pain Diseases 0.000 claims description 8
- 208000026935 allergic disease Diseases 0.000 claims description 8
- 206010003119 arrhythmia Diseases 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 8
- 230000002981 neuropathic effect Effects 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 8
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 7
- 206010035664 Pneumonia Diseases 0.000 claims description 7
- 206010037660 Pyrexia Diseases 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 7
- 230000035939 shock Effects 0.000 claims description 7
- 208000030507 AIDS Diseases 0.000 claims description 6
- 206010058019 Cancer Pain Diseases 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 102000008186 Collagen Human genes 0.000 claims description 6
- 108010035532 Collagen Proteins 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 201000004624 Dermatitis Diseases 0.000 claims description 6
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 6
- 208000007514 Herpes zoster Diseases 0.000 claims description 6
- 208000032571 Infant acute respiratory distress syndrome Diseases 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 206010027202 Meningitis bacterial Diseases 0.000 claims description 6
- 208000000112 Myalgia Diseases 0.000 claims description 6
- 206010028974 Neonatal respiratory distress syndrome Diseases 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 6
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 6
- 208000017442 Retinal disease Diseases 0.000 claims description 6
- 206010038923 Retinopathy Diseases 0.000 claims description 6
- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 206010069351 acute lung injury Diseases 0.000 claims description 6
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 6
- 230000007815 allergy Effects 0.000 claims description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 6
- 201000009904 bacterial meningitis Diseases 0.000 claims description 6
- 208000019664 bone resorption disease Diseases 0.000 claims description 6
- 229920001436 collagen Polymers 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 6
- 208000011379 keloid formation Diseases 0.000 claims description 6
- 208000017169 kidney disease Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 206010028417 myasthenia gravis Diseases 0.000 claims description 6
- 201000002652 newborn respiratory distress syndrome Diseases 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000008423 pleurisy Diseases 0.000 claims description 6
- 231100000241 scar Toxicity 0.000 claims description 6
- 230000009772 tissue formation Effects 0.000 claims description 6
- 208000019553 vascular disease Diseases 0.000 claims description 6
- 230000029663 wound healing Effects 0.000 claims description 6
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 5
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 208000008930 Low Back Pain Diseases 0.000 claims description 5
- 208000019693 Lung disease Diseases 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 208000000450 Pelvic Pain Diseases 0.000 claims description 5
- 206010036105 Polyneuropathy Diseases 0.000 claims description 5
- 206010065016 Post-traumatic pain Diseases 0.000 claims description 5
- 206010039203 Road traffic accident Diseases 0.000 claims description 5
- 208000008765 Sciatica Diseases 0.000 claims description 5
- 206010040070 Septic Shock Diseases 0.000 claims description 5
- 206010047163 Vasospasm Diseases 0.000 claims description 5
- 230000006793 arrhythmia Effects 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 230000000968 intestinal effect Effects 0.000 claims description 5
- 230000036210 malignancy Effects 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 230000007824 polyneuropathy Effects 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 230000003966 vascular damage Effects 0.000 claims description 5
- CRKZWUIHRZLAJZ-IOSLPCCCSA-N (2r,3r,4r,5r)-5-(6-amino-2-methoxypurin-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)=NC(N)=C2N=C1 CRKZWUIHRZLAJZ-IOSLPCCCSA-N 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000007101 Muscle Cramp Diseases 0.000 claims description 4
- 230000008485 antagonism Effects 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 210000002540 macrophage Anatomy 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 230000010412 perfusion Effects 0.000 claims description 4
- 230000001737 promoting effect Effects 0.000 claims description 4
- 230000008695 pulmonary vasoconstriction Effects 0.000 claims description 4
- 230000000638 stimulation Effects 0.000 claims description 4
- 230000001629 suppression Effects 0.000 claims description 4
- OTQBHDVRZNILNA-JJNLEZRASA-N (2r,3r,4r,5r)-5-[6-amino-2-(2,2-difluoroethoxy)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(OCC(F)F)=NC(N)=C2N=C1 OTQBHDVRZNILNA-JJNLEZRASA-N 0.000 claims description 3
- 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 claims description 3
- XHRKJFWAUMXHHT-TWBCTODHSA-N (2r,3r,4r,5r)-5-[6-amino-2-[[(2s)-butan-2-yl]amino]purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound C12=NC(N[C@@H](C)CC)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1OC XHRKJFWAUMXHHT-TWBCTODHSA-N 0.000 claims description 3
- 206010000087 Abdominal pain upper Diseases 0.000 claims description 3
- 208000000884 Airway Obstruction Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 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 3
- 206010002329 Aneurysm Diseases 0.000 claims description 3
- 208000006820 Arthralgia Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 208000000003 Breakthrough pain Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010006448 Bronchiolitis Diseases 0.000 claims description 3
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
- 206010006482 Bronchospasm Diseases 0.000 claims description 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
- 206010008479 Chest Pain Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 3
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 206010052337 Diastolic dysfunction Diseases 0.000 claims description 3
- 208000000059 Dyspnea Diseases 0.000 claims description 3
- 206010013975 Dyspnoeas Diseases 0.000 claims description 3
- 208000005189 Embolism Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- 208000007530 Essential hypertension Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 3
- 208000037357 HIV infectious disease Diseases 0.000 claims description 3
- 206010019027 Haemothorax Diseases 0.000 claims description 3
- 208000004575 Infectious Arthritis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 206010022562 Intermittent claudication Diseases 0.000 claims description 3
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 208000007914 Labor Pain Diseases 0.000 claims description 3
- 208000035945 Labour pain Diseases 0.000 claims description 3
- 201000008197 Laryngitis Diseases 0.000 claims description 3
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims description 3
- 208000016604 Lyme disease Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 206010028116 Mucosal inflammation Diseases 0.000 claims description 3
- 201000010927 Mucositis Diseases 0.000 claims description 3
- 206010049565 Muscle fatigue Diseases 0.000 claims description 3
- 206010028735 Nasal congestion Diseases 0.000 claims description 3
- 206010028836 Neck pain Diseases 0.000 claims description 3
- 208000012902 Nervous system disease Diseases 0.000 claims description 3
- 206010061876 Obstruction Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 206010033647 Pancreatitis acute Diseases 0.000 claims description 3
- 206010033799 Paralysis Diseases 0.000 claims description 3
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
- 208000004983 Phantom Limb Diseases 0.000 claims description 3
- 206010056238 Phantom pain Diseases 0.000 claims description 3
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 206010038419 Renal colic Diseases 0.000 claims description 3
- 206010038563 Reocclusion Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 201000010001 Silicosis Diseases 0.000 claims description 3
- 208000007718 Stable Angina Diseases 0.000 claims description 3
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 3
- 206010071436 Systolic dysfunction Diseases 0.000 claims description 3
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 3
- 208000028911 Temporomandibular Joint disease Diseases 0.000 claims description 3
- 208000001435 Thromboembolism Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 208000024716 acute asthma Diseases 0.000 claims description 3
- 201000003229 acute pancreatitis Diseases 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 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 3
- 229960003942 amphotericin b Drugs 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 206010003230 arteritis Diseases 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 3
- 230000002917 arthritic effect Effects 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 230000017531 blood circulation Effects 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 230000007885 bronchoconstriction Effects 0.000 claims description 3
- 208000023819 chronic asthma Diseases 0.000 claims description 3
- 208000007451 chronic bronchitis Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 230000007812 deficiency Effects 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 210000003979 eosinophil Anatomy 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 230000002008 hemorrhagic effect Effects 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 3
- 230000009610 hypersensitivity Effects 0.000 claims description 3
- 208000000509 infertility Diseases 0.000 claims description 3
- 230000036512 infertility Effects 0.000 claims description 3
- 231100000535 infertility Toxicity 0.000 claims description 3
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 208000030175 lameness Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 210000000440 neutrophil Anatomy 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 208000008494 pericarditis Diseases 0.000 claims description 3
- 230000002085 persistent effect Effects 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 206010035653 pneumoconiosis Diseases 0.000 claims description 3
- 201000003144 pneumothorax Diseases 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 230000010410 reperfusion Effects 0.000 claims description 3
- 230000010076 replication Effects 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 201000001223 septic arthritis Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 230000036262 stenosis Effects 0.000 claims description 3
- 208000037804 stenosis Diseases 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 239000003053 toxin Substances 0.000 claims description 3
- 231100000765 toxin Toxicity 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 3
- 239000002753 trypsin inhibitor Substances 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 208000001319 vasomotor rhinitis Diseases 0.000 claims description 3
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 claims description 3
- FODIJMMSPSLJKT-XNIJJKJLSA-N (2r,3r,4r,5r)-5-[6-amino-2-(2,5-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(=CC=C(F)C=3)F)=NC(N)=C2N=C1 FODIJMMSPSLJKT-XNIJJKJLSA-N 0.000 claims description 2
- 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 claims description 2
- 229930024421 Adenine Natural products 0.000 claims description 2
- 206010059245 Angiopathy Diseases 0.000 claims description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
- 206010010904 Convulsion Diseases 0.000 claims description 2
- 206010038669 Respiratory arrest Diseases 0.000 claims description 2
- 208000010513 Stupor Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 229960000643 adenine Drugs 0.000 claims description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 2
- 230000036461 convulsion Effects 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 230000000414 obstructive effect Effects 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 8
- 230000002939 deleterious effect Effects 0.000 claims 8
- 229940123907 Disease modifying antirheumatic drug Drugs 0.000 claims 6
- 229940126601 medicinal product Drugs 0.000 claims 6
- 206010006811 Bursitis Diseases 0.000 claims 4
- 206010050219 Lumbar radiculopathy Diseases 0.000 claims 4
- 201000002661 Spondylitis Diseases 0.000 claims 4
- 208000000491 Tendinopathy Diseases 0.000 claims 4
- 206010043255 Tendonitis Diseases 0.000 claims 4
- 208000026816 acute arthritis Diseases 0.000 claims 4
- 208000013465 muscle pain Diseases 0.000 claims 4
- 201000004415 tendinitis Diseases 0.000 claims 4
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 claims 3
- 206010061666 Autonomic neuropathy Diseases 0.000 claims 2
- 208000036004 Cow milk intolerance Diseases 0.000 claims 2
- 102100020873 Interleukin-2 Human genes 0.000 claims 2
- 206010061339 Perineal pain Diseases 0.000 claims 2
- 206010037423 Pulmonary oedema Diseases 0.000 claims 2
- 208000005392 Spasm Diseases 0.000 claims 2
- 201000009267 bronchiectasis Diseases 0.000 claims 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims 2
- 230000003090 exacerbative effect Effects 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 230000009401 metastasis Effects 0.000 claims 2
- 208000005333 pulmonary edema Diseases 0.000 claims 2
- 201000003068 rheumatic fever Diseases 0.000 claims 2
- 230000000391 smoking effect Effects 0.000 claims 2
- TUDKBZAMOFJOSO-UHFFFAOYSA-N 2-methoxy-7h-purin-6-amine Chemical compound COC1=NC(N)=C2NC=NC2=N1 TUDKBZAMOFJOSO-UHFFFAOYSA-N 0.000 claims 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 1
- 206010056677 Nerve degeneration Diseases 0.000 claims 1
- 208000024248 Vascular System injury Diseases 0.000 claims 1
- 208000012339 Vascular injury Diseases 0.000 claims 1
- 230000001364 causal effect Effects 0.000 claims 1
- 238000011109 contamination Methods 0.000 claims 1
- 210000004153 islets of langerhan Anatomy 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 abstract description 102
- 239000000651 prodrug Substances 0.000 abstract description 102
- 239000003435 antirheumatic agent Substances 0.000 abstract description 20
- 239000003379 purinergic P1 receptor agonist Substances 0.000 abstract description 18
- 230000000202 analgesic effect Effects 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 229940122614 Adenosine receptor agonist Drugs 0.000 abstract description 4
- 150000003838 adenosines Chemical class 0.000 abstract 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 abstract 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 abstract description 3
- 229940126701 oral medication Drugs 0.000 abstract description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
- 239000002207 metabolite Substances 0.000 description 62
- 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 44
- 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 36
- 230000036470 plasma concentration Effects 0.000 description 28
- AJACDNCVEGIBNA-UHFFFAOYSA-N 2-Methoxyadenosine Natural products C12=NC(OC)=NC(N)=C2N=CN1C1OC(CO)C(O)C1O AJACDNCVEGIBNA-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 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 26
- 229940079593 drug Drugs 0.000 description 25
- 102000005962 receptors Human genes 0.000 description 25
- 108020003175 receptors Proteins 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 22
- 229960005305 adenosine Drugs 0.000 description 22
- 239000012071 phase Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- 239000000725 suspension Substances 0.000 description 12
- 101150051188 Adora2a gene Proteins 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 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
- 239000002777 nucleoside Substances 0.000 description 10
- 230000002441 reversible effect Effects 0.000 description 10
- 229960001052 streptozocin Drugs 0.000 description 10
- 239000000556 agonist Substances 0.000 description 9
- 229940035676 analgesics Drugs 0.000 description 9
- 239000000730 antalgic agent 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
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 150000003833 nucleoside derivatives Chemical class 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
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000036543 hypotension Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 230000003389 potentiating effect Effects 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 241000282326 Felis catus Species 0.000 description 6
- 208000001871 Tachycardia Diseases 0.000 description 6
- 240000007591 Tilia tomentosa Species 0.000 description 6
- 150000003835 adenosine derivatives Chemical class 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
- 210000001503 joint Anatomy 0.000 description 6
- 230000003068 static effect Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 101150007969 ADORA1 gene Proteins 0.000 description 5
- 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 5
- 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 5
- 230000004913 activation Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000037324 pain perception Effects 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 229960000329 ribavirin Drugs 0.000 description 5
- 230000001953 sensory effect Effects 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010003840 Autonomic nervous system imbalance Diseases 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 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
- 230000009471 action Effects 0.000 description 4
- 230000003070 anti-hyperalgesia Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000036471 bradycardia Effects 0.000 description 4
- 208000006218 bradycardia Diseases 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 229940127240 opiate Drugs 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229940044601 receptor agonist Drugs 0.000 description 4
- 239000000018 receptor agonist Substances 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 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 4
- 229950006081 taribavirin Drugs 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229940093257 valacyclovir Drugs 0.000 description 4
- 0 *[C@@]([C@@]1O)O[C@@](CO)[C@@]1O Chemical compound *[C@@]([C@@]1O)O[C@@](CO)[C@@]1O 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
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 3
- 102000055025 Adenosine deaminases Human genes 0.000 description 3
- 241000282412 Homo Species 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
- 239000013543 active substance Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000007975 buffered saline Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000009931 harmful effect Effects 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
- 238000004949 mass spectrometry Methods 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
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000003826 tablet Substances 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
- 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
- CKTSBUTUHBMZGZ-CHKWXVPMSA-N 4-amino-1-[(2s,4r,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 CKTSBUTUHBMZGZ-CHKWXVPMSA-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
- 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
- 241000282693 Cercopithecidae Species 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
- 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
- 241000475481 Nebula Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000906034 Orthops Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 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
- 208000034189 Sclerosis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 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
- 150000007513 acids Chemical class 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
- 239000002582 adenosine A1 receptor agonist Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000004429 atom Chemical group 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
- 125000002619 bicyclic group Chemical group 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
- 238000004364 calculation method Methods 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
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003218 coronary vasodilator agent Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000753 cycloalkyl 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
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229910052731 fluorine Inorganic materials 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
- 125000002887 hydroxy group Chemical group [H]O* 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
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 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
- 239000003550 marker Substances 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 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
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 238000012544 monitoring process Methods 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
- 125000003835 nucleoside group Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000001044 sensory neuron Anatomy 0.000 description 2
- 238000000926 separation method Methods 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
- 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
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229930192474 thiophene Natural products 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
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical group [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- 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
- VRVYGUJRRXCMIH-IOSLPCCCSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2-hydroxyethoxy)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(OCCO)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VRVYGUJRRXCMIH-IOSLPCCCSA-N 0.000 description 1
- OASLHFBNUHASOX-HIDXMTOYSA-N (2r,3r,4s,5r)-2-[6-amino-6-(cyclopentylamino)-8h-purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N1=CN=C2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)CN=C2C1(N)NC1CCCC1 OASLHFBNUHASOX-HIDXMTOYSA-N 0.000 description 1
- BHRZNVHARXXAHW-BYPYZUCNSA-N (2s)-butan-2-amine Chemical compound CC[C@H](C)N BHRZNVHARXXAHW-BYPYZUCNSA-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
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 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
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 description 1
- 125000006705 (C5-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
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-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
- 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
- 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
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-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
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-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
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 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
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- LVCNGHBRNGEKCO-UHFFFAOYSA-N 4-methoxyoxolan-3-ol Chemical compound COC1COCC1O LVCNGHBRNGEKCO-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 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
- 102000030814 Adenosine A1 receptor Human genes 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
- DZPXXDUAQFAGFO-UHFFFAOYSA-N C1=CC=C2OCCC2=C1.C1=CC=C2OC=CC2=C1 Chemical compound C1=CC=C2OCCC2=C1.C1=CC=C2OC=CC2=C1 DZPXXDUAQFAGFO-UHFFFAOYSA-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
- 241000700198 Cavia 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
- 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
- 206010012335 Dependence Diseases 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010054261 Flavivirus infection Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010070840 Gastrointestinal tract irritation 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
- 101000821899 Homo sapiens Solute carrier family 15 member 1 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- 206010021118 Hypotonia 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
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 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
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 201000007100 Pharyngitis Diseases 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
- 102100021491 Solute carrier family 15 member 1 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
- 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
- 241000534944 Thia Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 241000700605 Viruses Species 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
- 230000003574 anti-allodynic effect Effects 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
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 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
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 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
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000002238 attenuated effect Effects 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
- 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
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 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
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 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
- 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
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 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
- 230000007883 bronchodilation Effects 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
- 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
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 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
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008602 contraction 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
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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
- 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
- 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
- SOVOPSCRHKEUNJ-UHFFFAOYSA-N dec-4-ene Chemical compound CCCCCC=CCCC SOVOPSCRHKEUNJ-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction 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
- 230000003292 diminished effect Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 239000003596 drug target Substances 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
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 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
- 238000002474 experimental method Methods 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010575 fractional recrystallization 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
- 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
- 210000002837 heart atrium Anatomy 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 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
- 230000000917 hyperalgesic 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
- 230000031891 intestinal absorption Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 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
- 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
- 230000000366 juvenile effect Effects 0.000 description 1
- 238000002372 labelling Methods 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
- 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
- 150000002632 lipids Chemical class 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
- 208000019267 mild heart failure Diseases 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000002266 mite infestation Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000036640 muscle relaxation Effects 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
- 230000008764 nerve damage Effects 0.000 description 1
- 230000003961 neuronal insult Effects 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
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 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
- 230000003287 optical effect Effects 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
- 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
- 230000007170 pathology Effects 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
- 108010082406 peptide permease Proteins 0.000 description 1
- 230000002093 peripheral effect 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
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000000843 powder Substances 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
- 229960001233 pregabalin Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 239000012264 purified product Substances 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
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 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
- 239000012266 salt solution Substances 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
- 210000002966 serum Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 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
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 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
- 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
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 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
- 235000012222 talc Nutrition 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
- 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
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- SRPWOOOHEPICQU-UHFFFAOYSA-N trimellitic anhydride Chemical compound OC(=O)C1=CC=C2C(=O)OC(=O)C2=C1 SRPWOOOHEPICQU-UHFFFAOYSA-N 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
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0601397 | 2006-06-27 | ||
| US83740206P | 2006-08-11 | 2006-08-11 | |
| PCT/EP2007/056377 WO2008000744A2 (en) | 2006-06-27 | 2007-06-26 | 2-0'-methyladen0sine derivatives and their use as agonists or antagonists of an adenosine receptor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009541437A true JP2009541437A (ja) | 2009-11-26 |
| JP2009541437A5 JP2009541437A5 (https=) | 2010-08-05 |
Family
ID=38573394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009517174A Withdrawn JP2009541437A (ja) | 2006-06-27 | 2007-06-26 | 治療用化合物 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US7820811B2 (https=) |
| EP (1) | EP2081932A2 (https=) |
| JP (1) | JP2009541437A (https=) |
| CN (1) | CN101479268B (https=) |
| AU (1) | AU2007263727A1 (https=) |
| BR (1) | BRPI0713902A2 (https=) |
| CA (1) | CA2654371A1 (https=) |
| NZ (1) | NZ573307A (https=) |
| RU (1) | RU2009102536A (https=) |
| WO (1) | WO2008000744A2 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2007263728A1 (en) * | 2006-06-27 | 2008-01-03 | Biovitrum Ab (Publ) | Adenosine derivatives for the treatment of pain |
| WO2012048013A2 (en) * | 2010-10-06 | 2012-04-12 | Inhibitex, Inc. | Phosphorodiamidate derivatives of guanosine nucleoside compounds for treatment of viral injections |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4843066A (en) | 1986-11-27 | 1989-06-27 | Nippon Zoki Pharmaceutical Co., Ltd. | Novel adenosine derivatives and pharmaceutical composition containing them as an active ingredient |
| US5968914A (en) | 1987-10-28 | 1999-10-19 | Pro-Neuron, Inc. | Treatment of chemotherapeutic agent and antiviral agent toxicity with acylated pyrimidine nucleosides |
| ATE269870T1 (de) * | 1989-10-24 | 2004-07-15 | Isis Pharmaceuticals Inc | 2'-modifizierte oligonukleotide |
| HUT61567A (en) | 1990-12-07 | 1993-01-28 | Sandoz Ag | Process for producing new pharmaceutical compositions comprising 2'-o-alkyladenosine derivatives and for producing 6-cyclohexyl-2'-o-methyladenosinehydrate |
| EP0601322A3 (en) | 1992-10-27 | 1994-10-12 | Nippon Zoki Pharmaceutical Co | Adenosine deaminase inhibitor. |
| US5877180A (en) | 1994-07-11 | 1999-03-02 | University Of Virginia Patent Foundation | Method for treating inflammatory diseases with A2a adenosine receptor agonists |
| ATE236922T1 (de) | 1997-06-03 | 2003-04-15 | Itochu Techno Chem Inc | Natürliche antitumor- oder antivirale substanzen und ihre anwendung |
| US6576619B2 (en) | 1999-05-24 | 2003-06-10 | Cv Therapeutics, Inc. | Orally active A1 adenosine receptor agonists |
| MXPA04012779A (es) | 2002-06-28 | 2005-08-19 | Idenix Cayman Ltd | Profarmacos de 2'- y 3'-nucleosido para tratar infecciones por flaviviridae. |
| GB0228723D0 (en) | 2002-12-09 | 2003-01-15 | Cambridge Biotechnology Ltd | Treatment of pain |
| GB0305150D0 (en) | 2003-03-07 | 2003-04-09 | Cambridge Biotechnology Ltd | Use of therapeutic compounds |
| GB0305153D0 (en) | 2003-03-07 | 2003-04-09 | Cambridge Biotechnology Ltd | Identification of therapeutic compounds |
| GB0305149D0 (en) | 2003-03-07 | 2003-04-09 | Cambridge Biotechnology Ltd | Compounds for the treatment of pain |
| GB0328323D0 (en) | 2003-12-05 | 2004-01-07 | Cambridge Biotechnology Ltd | Synthesis of 2-substituted adenosines |
| CA2557285A1 (en) * | 2004-03-05 | 2005-09-15 | Cambridge Biotechnology Limited | Adenosine receptor agonists |
| AU2007263728A1 (en) * | 2006-06-27 | 2008-01-03 | Biovitrum Ab (Publ) | Adenosine derivatives for the treatment of pain |
-
2007
- 2007-06-26 BR BRPI0713902-0A patent/BRPI0713902A2/pt not_active IP Right Cessation
- 2007-06-26 US US11/823,191 patent/US7820811B2/en not_active Expired - Fee Related
- 2007-06-26 NZ NZ573307A patent/NZ573307A/en not_active IP Right Cessation
- 2007-06-26 EP EP07786849A patent/EP2081932A2/en not_active Withdrawn
- 2007-06-26 CN CN2007800239044A patent/CN101479268B/zh not_active Expired - Fee Related
- 2007-06-26 WO PCT/EP2007/056377 patent/WO2008000744A2/en not_active Ceased
- 2007-06-26 JP JP2009517174A patent/JP2009541437A/ja not_active Withdrawn
- 2007-06-26 RU RU2009102536/04A patent/RU2009102536A/ru not_active Application Discontinuation
- 2007-06-26 AU AU2007263727A patent/AU2007263727A1/en not_active Abandoned
- 2007-06-26 CA CA002654371A patent/CA2654371A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008000744A2 (en) | 2008-01-03 |
| BRPI0713902A2 (pt) | 2012-11-27 |
| US20080009461A1 (en) | 2008-01-10 |
| NZ573307A (en) | 2012-02-24 |
| CA2654371A1 (en) | 2008-01-03 |
| WO2008000744A3 (en) | 2008-02-28 |
| RU2009102536A (ru) | 2010-08-10 |
| CN101479268A (zh) | 2009-07-08 |
| CN101479268B (zh) | 2012-08-08 |
| US7820811B2 (en) | 2010-10-26 |
| EP2081932A2 (en) | 2009-07-29 |
| AU2007263727A1 (en) | 2008-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chandra et al. | Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs | |
| CN101056879B (zh) | 作为a3和a1腺苷受体激动剂的嘌呤衍生物 | |
| AU746590B2 (en) | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties | |
| US7906518B2 (en) | Therapeutic compounds | |
| JP2007526291A (ja) | アデノシン受容体アゴニスト | |
| US6376472B1 (en) | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties | |
| RU2441875C2 (ru) | Терапевтические соединения | |
| SK14052003A3 (sk) | Použitie derivátov adenozínu na prípravu liečiva na liečenie syndrómu inzulínovej rezistencie a diabetu | |
| JP2024515786A (ja) | プリンヌクレオシド、それらの中間体、およびそれらの調製方法 | |
| JP2009541437A (ja) | 治療用化合物 | |
| CN1364170A (zh) | 噻吩a2a受体激动剂 | |
| HK1129109A (en) | 2-0'-methyladenosine derivatives and their use as agonists or antagonists of an adenosine receptor | |
| HK1129117A (en) | Novel 2',3'-methylidene acetyl adenosine prodrugs for use as prodrugs for adenosine receptor agonists novel 2',3'-methylidene acetyl adenosine prodrugs for use as prodrugs for adenosine receptor agonists | |
| Nkomba et al. | Design, synthesis and evaluation of amino-3, 5-dicyanopyryridines and thieno [2, 3-b] pyridines as ligands of adenosine receptors | |
| Tchilibon et al. | J Med Chem. Author manuscript; available in PMC 2012 October 03. Published in final edited form as: J Med Chem. 2005 March 24; 48 (6): 1745–1758. doi: 10.1021/jm049580r. | |
| HK1129228A (en) | Therapeutic compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100616 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100616 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20110714 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20120726 |