AU2007263728A1 - Adenosine derivatives for the treatment of pain - Google Patents
Adenosine derivatives for the treatment of pain Download PDFInfo
- Publication number
- AU2007263728A1 AU2007263728A1 AU2007263728A AU2007263728A AU2007263728A1 AU 2007263728 A1 AU2007263728 A1 AU 2007263728A1 AU 2007263728 A AU2007263728 A AU 2007263728A AU 2007263728 A AU2007263728 A AU 2007263728A AU 2007263728 A1 AU2007263728 A1 AU 2007263728A1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- pain
- produce
- protecting
- 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.)
- Abandoned
Links
- 208000002193 Pain Diseases 0.000 title claims description 45
- 230000036407 pain Effects 0.000 title claims description 44
- 150000003835 adenosine derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 239
- 230000000694 effects Effects 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 42
- 239000000047 product Substances 0.000 claims description 38
- 108050000203 Adenosine receptors Proteins 0.000 claims description 35
- 102000009346 Adenosine receptors Human genes 0.000 claims description 34
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 31
- 239000007795 chemical reaction product Substances 0.000 claims description 27
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 239000002988 disease modifying antirheumatic drug Substances 0.000 claims description 23
- 230000036470 plasma concentration Effects 0.000 claims description 23
- -1 trifluoromethylphenyl Chemical group 0.000 claims description 23
- 206010061218 Inflammation Diseases 0.000 claims description 22
- 230000004054 inflammatory process Effects 0.000 claims description 22
- 230000006378 damage Effects 0.000 claims description 21
- 102000007471 Adenosine A2A receptor Human genes 0.000 claims description 19
- 108010085277 Adenosine A2A receptor Proteins 0.000 claims description 19
- 206010012601 diabetes mellitus Diseases 0.000 claims description 18
- 210000001519 tissue Anatomy 0.000 claims description 17
- MGEBVSZZNFOIRB-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(6-amino-2-iodopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(I)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O MGEBVSZZNFOIRB-UUOKFMHZSA-N 0.000 claims description 16
- 208000028867 ischemia Diseases 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 16
- 230000001575 pathological effect Effects 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 208000004454 Hyperalgesia Diseases 0.000 claims description 11
- 208000035154 Hyperesthesia Diseases 0.000 claims description 11
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 11
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 claims description 11
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 201000001320 Atherosclerosis Diseases 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 10
- 201000008482 osteoarthritis Diseases 0.000 claims description 10
- JKIGHOARKAIPJI-UHFFFAOYSA-N (3,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C(Cl)=C1 JKIGHOARKAIPJI-UHFFFAOYSA-N 0.000 claims description 9
- 206010063837 Reperfusion injury Diseases 0.000 claims description 9
- 208000001871 Tachycardia Diseases 0.000 claims description 9
- 208000036142 Viral infection Diseases 0.000 claims description 9
- 230000002411 adverse Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 230000009385 viral infection Effects 0.000 claims description 9
- 206010001513 AIDS related complex Diseases 0.000 claims description 8
- 206010002383 Angina Pectoris Diseases 0.000 claims description 8
- 201000005569 Gout Diseases 0.000 claims description 8
- 210000004027 cell Anatomy 0.000 claims description 8
- 230000000302 ischemic effect Effects 0.000 claims description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 208000021722 neuropathic pain Diseases 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 8
- 230000006794 tachycardia Effects 0.000 claims description 8
- 208000035143 Bacterial infection Diseases 0.000 claims description 7
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 7
- 208000001953 Hypotension Diseases 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 7
- 230000036543 hypotension Effects 0.000 claims description 7
- 210000004072 lung Anatomy 0.000 claims description 7
- 230000002981 neuropathic effect Effects 0.000 claims description 7
- 230000000451 tissue damage Effects 0.000 claims description 7
- 231100000827 tissue damage Toxicity 0.000 claims description 7
- PXFJLKKZSWWVRX-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1N1CCNCC1 PXFJLKKZSWWVRX-UHFFFAOYSA-N 0.000 claims description 6
- PKRRNTJIHGOMRC-UHFFFAOYSA-N 1-benzofuran-2-ylboronic acid Chemical compound C1=CC=C2OC(B(O)O)=CC2=C1 PKRRNTJIHGOMRC-UHFFFAOYSA-N 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
- 208000036487 Arthropathies Diseases 0.000 claims description 6
- 206010006895 Cachexia Diseases 0.000 claims description 6
- 206010063094 Cerebral malaria Diseases 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 208000012659 Joint disease Diseases 0.000 claims description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 6
- 230000001363 autoimmune Effects 0.000 claims description 6
- 206010006451 bronchitis Diseases 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- BHRZNVHARXXAHW-BYPYZUCNSA-N (2s)-butan-2-amine Chemical compound CC[C@H](C)N BHRZNVHARXXAHW-BYPYZUCNSA-N 0.000 claims description 5
- UHDDEIOYXFXNNJ-UHFFFAOYSA-N (3,4,5-trifluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=C(F)C(F)=C1 UHDDEIOYXFXNNJ-UHFFFAOYSA-N 0.000 claims description 5
- QWQBQRYFWNIDOC-UHFFFAOYSA-N (3,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC(F)=C1 QWQBQRYFWNIDOC-UHFFFAOYSA-N 0.000 claims description 5
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims description 5
- 206010061666 Autonomic neuropathy Diseases 0.000 claims description 5
- 208000008035 Back Pain Diseases 0.000 claims description 5
- 208000001640 Fibromyalgia Diseases 0.000 claims description 5
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 208000004550 Postoperative Pain Diseases 0.000 claims description 5
- 208000017442 Retinal disease Diseases 0.000 claims description 5
- 206010038923 Retinopathy Diseases 0.000 claims description 5
- 210000004204 blood vessel Anatomy 0.000 claims description 5
- 230000036471 bradycardia Effects 0.000 claims description 5
- 208000006218 bradycardia Diseases 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 230000002685 pulmonary effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 208000019553 vascular disease Diseases 0.000 claims description 5
- 230000029663 wound healing Effects 0.000 claims description 5
- BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
- 206010058019 Cancer Pain Diseases 0.000 claims description 4
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 201000009273 Endometriosis Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000007514 Herpes zoster Diseases 0.000 claims description 4
- 208000032571 Infant acute respiratory distress syndrome Diseases 0.000 claims description 4
- 206010022562 Intermittent claudication Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010027202 Meningitis bacterial Diseases 0.000 claims description 4
- 208000007101 Muscle Cramp Diseases 0.000 claims description 4
- 208000000112 Myalgia Diseases 0.000 claims description 4
- 206010028974 Neonatal respiratory distress syndrome Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 208000000450 Pelvic Pain Diseases 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 4
- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- BPTABBGLHGBJQR-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BPTABBGLHGBJQR-UHFFFAOYSA-N 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 230000008484 agonism Effects 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 206010003119 arrhythmia Diseases 0.000 claims description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 201000009904 bacterial meningitis Diseases 0.000 claims description 4
- 208000019664 bone resorption disease Diseases 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
- 208000011379 keloid formation Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 230000036210 malignancy Effects 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 201000002652 newborn respiratory distress syndrome Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 208000008423 pleurisy Diseases 0.000 claims description 4
- 230000008695 pulmonary vasoconstriction Effects 0.000 claims description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 4
- 231100000241 scar Toxicity 0.000 claims description 4
- 230000009772 tissue formation Effects 0.000 claims description 4
- BDDVAWDNVWLHDQ-UHFFFAOYSA-N 2-chloro-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C(Cl)=C1 BDDVAWDNVWLHDQ-UHFFFAOYSA-N 0.000 claims description 3
- WDNBURPWRNALGP-UHFFFAOYSA-N 3,4-Dichlorophenol Chemical compound OC1=CC=C(Cl)C(Cl)=C1 WDNBURPWRNALGP-UHFFFAOYSA-N 0.000 claims description 3
- ODSXJQYJADZFJX-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)phenol Chemical compound OC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ODSXJQYJADZFJX-UHFFFAOYSA-N 0.000 claims description 3
- ADMXVFQXBMAXJX-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]phenol Chemical compound OC1=CC=CC(C=2C=CC(=CC=2)C(F)(F)F)=C1 ADMXVFQXBMAXJX-UHFFFAOYSA-N 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- 208000006820 Arthralgia Diseases 0.000 claims description 3
- 206010006811 Bursitis Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 208000008930 Low Back Pain Diseases 0.000 claims description 3
- 208000019693 Lung disease Diseases 0.000 claims description 3
- 206010036105 Polyneuropathy Diseases 0.000 claims description 3
- 206010039203 Road traffic accident Diseases 0.000 claims description 3
- 208000008765 Sciatica Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 208000000491 Tendinopathy Diseases 0.000 claims description 3
- 206010043255 Tendonitis Diseases 0.000 claims description 3
- 208000026816 acute arthritis Diseases 0.000 claims description 3
- 230000001775 anti-pathogenic effect Effects 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 230000010412 perfusion Effects 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 230000007824 polyneuropathy Effects 0.000 claims description 3
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 claims description 3
- 241000894007 species Species 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 201000004415 tendinitis Diseases 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- INXKVYFOWNAVMU-UHFFFAOYSA-N 2,5-difluorophenol Chemical compound OC1=CC(F)=CC=C1F INXKVYFOWNAVMU-UHFFFAOYSA-N 0.000 claims description 2
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 claims description 2
- 206010000087 Abdominal pain upper Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 2
- 206010002329 Aneurysm Diseases 0.000 claims description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000000003 Breakthrough pain Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- 206010006482 Bronchospasm Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
- 206010008479 Chest Pain Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims description 2
- 206010052337 Diastolic dysfunction Diseases 0.000 claims description 2
- 206010014561 Emphysema Diseases 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 208000007530 Essential hypertension Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000037357 HIV infectious disease Diseases 0.000 claims description 2
- 206010019027 Haemothorax Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010058179 Hypertensive emergency Diseases 0.000 claims description 2
- 208000004575 Infectious Arthritis Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 108010002350 Interleukin-2 Proteins 0.000 claims description 2
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 2
- 206010023125 Jarisch-Herxheimer reaction Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 208000007914 Labor Pain Diseases 0.000 claims description 2
- 201000008197 Laryngitis Diseases 0.000 claims description 2
- 206010050219 Lumbar radiculopathy Diseases 0.000 claims description 2
- 208000016604 Lyme disease Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010027476 Metastases Diseases 0.000 claims description 2
- 206010028116 Mucosal inflammation Diseases 0.000 claims description 2
- 201000010927 Mucositis Diseases 0.000 claims description 2
- 206010049565 Muscle fatigue Diseases 0.000 claims description 2
- 208000030858 Myofascial Pain Syndromes Diseases 0.000 claims description 2
- 206010028735 Nasal congestion Diseases 0.000 claims description 2
- 206010028836 Neck pain Diseases 0.000 claims description 2
- 206010029888 Obliterative bronchiolitis Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 206010061339 Perineal pain Diseases 0.000 claims description 2
- 208000004983 Phantom Limb Diseases 0.000 claims description 2
- 206010056238 Phantom pain Diseases 0.000 claims description 2
- 208000002151 Pleural effusion Diseases 0.000 claims description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010038563 Reocclusion Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 206010048908 Seasonal allergy Diseases 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
- 208000007718 Stable Angina Diseases 0.000 claims description 2
- 208000005279 Status Asthmaticus Diseases 0.000 claims description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 2
- 206010071436 Systolic dysfunction Diseases 0.000 claims description 2
- 208000001435 Thromboembolism Diseases 0.000 claims description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 206010047249 Venous thrombosis Diseases 0.000 claims description 2
- 208000024716 acute asthma Diseases 0.000 claims description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 2
- 229960003942 amphotericin b Drugs 0.000 claims description 2
- 238000002399 angioplasty Methods 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 206010003230 arteritis Diseases 0.000 claims description 2
- 230000002917 arthritic effect Effects 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 230000017531 blood circulation Effects 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 201000009267 bronchiectasis Diseases 0.000 claims description 2
- 201000003848 bronchiolitis obliterans Diseases 0.000 claims description 2
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims description 2
- 230000007885 bronchoconstriction Effects 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 208000023819 chronic asthma Diseases 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 208000024980 claudication Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 208000010247 contact dermatitis Diseases 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 210000003979 eosinophil Anatomy 0.000 claims description 2
- 230000004761 fibrosis Effects 0.000 claims description 2
- 230000002008 hemorrhagic effect Effects 0.000 claims description 2
- 230000002440 hepatic effect Effects 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
- 230000009610 hypersensitivity Effects 0.000 claims description 2
- 208000000509 infertility Diseases 0.000 claims description 2
- 230000036512 infertility Effects 0.000 claims description 2
- 231100000535 infertility Toxicity 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 239000002085 irritant Substances 0.000 claims description 2
- 231100000021 irritant Toxicity 0.000 claims description 2
- 210000004153 islets of langerhan Anatomy 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 201000005857 malignant hypertension Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 239000008267 milk Substances 0.000 claims description 2
- 210000004080 milk Anatomy 0.000 claims description 2
- 235000013336 milk Nutrition 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 201000001119 neuropathy Diseases 0.000 claims description 2
- 230000007823 neuropathy Effects 0.000 claims description 2
- 210000000440 neutrophil Anatomy 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 208000008494 pericarditis Diseases 0.000 claims description 2
- 208000030613 peripheral artery disease Diseases 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 230000002085 persistent effect Effects 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 206010035653 pneumoconiosis Diseases 0.000 claims description 2
- 201000003144 pneumothorax Diseases 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 230000010410 reperfusion Effects 0.000 claims description 2
- 230000010076 replication Effects 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 201000001223 septic arthritis Diseases 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 230000035939 shock Effects 0.000 claims description 2
- 201000009890 sinusitis Diseases 0.000 claims description 2
- 230000000391 smoking effect Effects 0.000 claims description 2
- 208000020431 spinal cord injury Diseases 0.000 claims description 2
- 208000005198 spinal stenosis Diseases 0.000 claims description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
- 239000002753 trypsin inhibitor Substances 0.000 claims description 2
- 231100000397 ulcer Toxicity 0.000 claims description 2
- 208000001319 vasomotor rhinitis Diseases 0.000 claims description 2
- 201000005539 vernal conjunctivitis Diseases 0.000 claims description 2
- 229940123907 Disease modifying antirheumatic drug Drugs 0.000 claims 4
- 201000002661 Spondylitis Diseases 0.000 claims 2
- 206010069351 acute lung injury Diseases 0.000 claims 2
- PSQZJKGXDGNDFP-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropan-1-ol Chemical compound OCC(F)(F)C(F)(F)F PSQZJKGXDGNDFP-UHFFFAOYSA-N 0.000 claims 1
- VOGSDFLJZPNWHY-UHFFFAOYSA-N 2,2-difluoroethanol Chemical compound OCC(F)F VOGSDFLJZPNWHY-UHFFFAOYSA-N 0.000 claims 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 102100020873 Interleukin-2 Human genes 0.000 claims 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims 1
- 206010033647 Pancreatitis acute Diseases 0.000 claims 1
- 206010037779 Radiculopathy Diseases 0.000 claims 1
- 208000028911 Temporomandibular Joint disease Diseases 0.000 claims 1
- 206010043220 Temporomandibular joint syndrome Diseases 0.000 claims 1
- 201000003229 acute pancreatitis Diseases 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 261
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 176
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 59
- 239000002904 solvent Substances 0.000 description 52
- 230000014759 maintenance of location Effects 0.000 description 42
- 239000012071 phase Substances 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 230000002441 reversible effect Effects 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- 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 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 22
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 22
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
- 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 20
- AJACDNCVEGIBNA-UHFFFAOYSA-N 2-Methoxyadenosine Natural products C12=NC(OC)=NC(N)=C2N=CN1C1OC(CO)C(O)C1O AJACDNCVEGIBNA-UHFFFAOYSA-N 0.000 description 20
- 239000003435 antirheumatic agent Substances 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 238000002953 preparative HPLC Methods 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 13
- 229960005305 adenosine Drugs 0.000 description 13
- 241000282326 Felis catus Species 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 12
- 230000000202 analgesic effect Effects 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 10
- 101150051188 Adora2a gene Proteins 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 229940035676 analgesics Drugs 0.000 description 9
- 239000000730 antalgic agent Substances 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- KUCWUAFNGCMZDB-UHFFFAOYSA-N 2-amino-3-nitrophenol Chemical compound NC1=C(O)C=CC=C1[N+]([O-])=O KUCWUAFNGCMZDB-UHFFFAOYSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 241000700159 Rattus Species 0.000 description 6
- 240000007591 Tilia tomentosa Species 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000001503 joint Anatomy 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 239000000018 receptor agonist Substances 0.000 description 6
- 229940044601 receptor agonist Drugs 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 150000003838 adenosines Chemical class 0.000 description 5
- 230000003070 anti-hyperalgesia Effects 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 description 5
- 230000037324 pain perception Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 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 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940127240 opiate Drugs 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000001953 sensory effect Effects 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 206010065390 Inflammatory pain Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000006198 methoxylation reaction 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
- 238000001953 recrystallisation Methods 0.000 description 3
- 210000001044 sensory neuron Anatomy 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 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 description 2
- 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 description 2
- 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 description 2
- UYCOIJFGQMELAP-LKGUXBDMSA-N (2r,3r,4s,5r)-2-[6-amino-2-(3,4,5-trifluorophenyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(C=3C=C(F)C(F)=C(F)C=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UYCOIJFGQMELAP-LKGUXBDMSA-N 0.000 description 2
- DDBXEDUAASXWOO-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-amino-2-(3,4-dichlorophenoxy)purin-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=C(Cl)C(Cl)=C1 DDBXEDUAASXWOO-SDBHATRESA-N 0.000 description 2
- XTFZXPGHKSNZQD-UBEDBUPSSA-N (2r,3r,4s,5r)-2-[6-amino-2-(3,4-dichlorophenyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(C=3C=C(Cl)C(Cl)=CC=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O XTFZXPGHKSNZQD-UBEDBUPSSA-N 0.000 description 2
- 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
- ACRYOOUGOIHYBD-UBEDBUPSSA-N (2r,3r,4s,5r)-2-[6-amino-2-[3,5-bis(trifluoromethyl)phenyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(C=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ACRYOOUGOIHYBD-UBEDBUPSSA-N 0.000 description 2
- NMBWHHWKWBOMPI-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-amino-2-[3-[4-(trifluoromethyl)phenyl]phenoxy]purin-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=1OC(C=1)=CC=CC=1C1=CC=C(C(F)(F)F)C=C1 NMBWHHWKWBOMPI-QTQZEZTPSA-N 0.000 description 2
- UYWABUWJWYGJQA-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-amino-2-[4-chloro-3-(trifluoromethyl)phenoxy]purin-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=C(Cl)C(C(F)(F)F)=C1 UYWABUWJWYGJQA-SDBHATRESA-N 0.000 description 2
- QDAILWHIHQEOLG-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-amino-2-[4-fluoro-3-(trifluoromethyl)phenoxy]purin-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=C(F)C(C(F)(F)F)=C1 QDAILWHIHQEOLG-SDBHATRESA-N 0.000 description 2
- COJBZAYNQJNHGF-OFBQIVOGSA-N (2r,3s,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methoxyoxolane-3,4-diol Chemical compound CO[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 COJBZAYNQJNHGF-OFBQIVOGSA-N 0.000 description 2
- FPUGCISOLXNPPC-IOSLPCCCSA-N 2'-methoxyadenosine Natural products CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FPUGCISOLXNPPC-IOSLPCCCSA-N 0.000 description 2
- VVDIZWFSGJERMA-UHFFFAOYSA-N 2-methyloxolane-3,4-diol Chemical compound CC1OCC(O)C1O VVDIZWFSGJERMA-UHFFFAOYSA-N 0.000 description 2
- XGYIMTFOTBMPFP-KQYNXXCUSA-N 5'-deoxyadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 XGYIMTFOTBMPFP-KQYNXXCUSA-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
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 241000906034 Orthops Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 229930003827 cannabinoid Natural products 0.000 description 2
- 239000003557 cannabinoid Substances 0.000 description 2
- 229940065144 cannabinoids Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- OFEZSBMBBKLLBJ-BAJZRUMYSA-N cordycepin Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)C[C@H]1O OFEZSBMBBKLLBJ-BAJZRUMYSA-N 0.000 description 2
- OFEZSBMBBKLLBJ-UHFFFAOYSA-N cordycepine Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)CC1O OFEZSBMBBKLLBJ-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 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 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229940048921 humira Drugs 0.000 description 2
- 230000000917 hyperalgesic effect Effects 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 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
- 230000003040 nociceptive effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000005425 toluyl group Chemical group 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- PVXJZKRUXHTVGR-XWXWGSFUSA-N (2r,3r,4s,5r)-2-[6-amino-2-(1-benzofuran-2-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(C=3OC4=CC=CC=C4C=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O PVXJZKRUXHTVGR-XWXWGSFUSA-N 0.000 description 1
- BGVUCFVKIBPRPR-KQYNXXCUSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2,2,3,3,3-pentafluoropropoxy)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(OCC(F)(F)C(F)(F)F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BGVUCFVKIBPRPR-KQYNXXCUSA-N 0.000 description 1
- KWLMCVOQKMQPEL-UBEDBUPSSA-N (2r,3r,4s,5r)-2-[6-amino-2-(3,5-difluorophenyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(C=3C=C(F)C=C(F)C=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KWLMCVOQKMQPEL-UBEDBUPSSA-N 0.000 description 1
- LHNZVKLBJXMMJR-FRJWGUMJSA-N (2r,3r,4s,5r)-2-[6-amino-2-(cyclopentylamino)purin-9-yl]-5-methyloxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C2=NC(NC3CCCC3)=NC(N)=C2N=C1 LHNZVKLBJXMMJR-FRJWGUMJSA-N 0.000 description 1
- YSOHVYMYTFPFNU-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-amino-2-[3,5-bis(trifluoromethyl)phenoxy]purin-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(C(F)(F)F)=CC(C(F)(F)F)=C1 YSOHVYMYTFPFNU-SDBHATRESA-N 0.000 description 1
- RBTVQGPVQRKBBU-NVQRDWNXSA-N (2r,3r,4s,5r)-2-[6-amino-2-[4-(3,4-dichlorophenyl)piperazin-1-yl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(N3CCN(CC3)C=3C=C(Cl)C(Cl)=CC=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RBTVQGPVQRKBBU-NVQRDWNXSA-N 0.000 description 1
- KRUDKTIKFACQRT-IMSIIYSGSA-N (2r,3r,5s)-2-[6-amino-2-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolan-3-ol Chemical compound N=1C=2N([C@H]3[C@@H](C[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NC1CCCC1 KRUDKTIKFACQRT-IMSIIYSGSA-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
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 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
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- RPEPGIOVXBBUMJ-UHFFFAOYSA-N 2,3-difluorophenol Chemical compound OC1=CC=CC(F)=C1F RPEPGIOVXBBUMJ-UHFFFAOYSA-N 0.000 description 1
- WJAOJLDJPQVXEX-UHFFFAOYSA-N 2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound COC1COC(CO)C1O WJAOJLDJPQVXEX-UHFFFAOYSA-N 0.000 description 1
- JZAORLZAMLPSNO-UHFFFAOYSA-N 2-[6-amino-2-(cyclopentylmethoxy)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound NC1=C2N=CN(C2=NC(=N1)OCC1CCCC1)C1(OCC(C1O)OC)CO JZAORLZAMLPSNO-UHFFFAOYSA-N 0.000 description 1
- 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 description 1
- FXTKWBZFNQHAAO-UHFFFAOYSA-N 3-iodophenol Chemical compound OC1=CC=CC(I)=C1 FXTKWBZFNQHAAO-UHFFFAOYSA-N 0.000 description 1
- KLXHXHUHLYWQMT-XNIJJKJLSA-N 4-[6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]oxy-2-chlorobenzonitrile 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=C(C#N)C(Cl)=C1 KLXHXHUHLYWQMT-XNIJJKJLSA-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
- DHPCRFYUUWAGAH-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)phenol Chemical compound OC1=CC=C(F)C(C(F)(F)F)=C1 DHPCRFYUUWAGAH-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 101150078577 Adora2b gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 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
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 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
- 206010018691 Granuloma Diseases 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 102100024007 Neurofilament heavy polypeptide Human genes 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 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
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 102000009270 Tumour necrosis factor alpha Human genes 0.000 description 1
- 108050000101 Tumour necrosis factor alpha Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- JNSBEPKGFVENFS-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC=C1C(F)(F)F JNSBEPKGFVENFS-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient 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
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
- 239000003855 balanced salt solution Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- 230000008081 blood perfusion 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
- 150000001669 calcium Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000005323 carbonate salts Chemical class 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 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
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 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
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000002565 electrocardiography Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass 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
- 230000036541 health Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 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
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000008101 lactose Substances 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
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 108010091047 neurofilament protein H Proteins 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 230000008533 pain sensitivity Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 229960001639 penicillamine Drugs 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate 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
- 230000001737 promoting effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 210000000278 spinal cord Anatomy 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
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 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
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000001738 temporomandibular joint Anatomy 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0601398 | 2006-06-27 | ||
| SE0601398-1 | 2006-06-27 | ||
| US83714606P | 2006-08-11 | 2006-08-11 | |
| US60/837,146 | 2006-08-11 | ||
| PCT/EP2007/056378 WO2008000745A2 (en) | 2006-06-27 | 2007-06-26 | Adenosine derivatives for the treatment of pain |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2007263728A1 true AU2007263728A1 (en) | 2008-01-03 |
Family
ID=38537489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007263728A Abandoned AU2007263728A1 (en) | 2006-06-27 | 2007-06-26 | Adenosine derivatives for the treatment of pain |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7807685B2 (https=) |
| EP (1) | EP2081946B1 (https=) |
| JP (1) | JP2009541438A (https=) |
| CN (1) | CN101479289A (https=) |
| AU (1) | AU2007263728A1 (https=) |
| CA (1) | CA2654375A1 (https=) |
| NZ (1) | NZ573308A (https=) |
| RU (1) | RU2441875C2 (https=) |
| WO (1) | WO2008000745A2 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0713902A2 (pt) * | 2006-06-27 | 2012-11-27 | Biovitrum Ab | compostos terapêuticos |
| US20100160351A1 (en) * | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Pharmaceutical compositions and methods for treating hyperuricemia and related disorders |
| WO2010071865A1 (en) | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Pharmaceutical compositions and methods for treating hyperuricemia and related disorders |
| WO2011032175A1 (en) | 2009-09-14 | 2011-03-17 | Nuon Therapeutics, Inc. | Combination formulations of tranilast and allopurinol and methods related thereto |
| US20140065223A1 (en) * | 2011-03-31 | 2014-03-06 | Jeanette Libera-Koerner | Perfluorinated compounds for the non-viral transfer of nucleic acids |
| US20150038445A1 (en) * | 2012-02-11 | 2015-02-05 | Academia Sinica | Methods and compositions for treating pain |
| CN113924309A (zh) * | 2019-05-21 | 2022-01-11 | 株式会社纳蒂亚斯 | 寡核苷酸合成中使用的多氟嵌段聚体以及使用其的寡核苷酸合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE269870T1 (de) * | 1989-10-24 | 2004-07-15 | Isis Pharmaceuticals Inc | 2'-modifizierte oligonukleotide |
| 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 |
| CA2361614C (en) * | 1999-02-01 | 2008-08-26 | University Of Virginia Patent Foundation | Compositions for treating inflammatory response |
| 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 |
| CA2557285A1 (en) | 2004-03-05 | 2005-09-15 | Cambridge Biotechnology Limited | Adenosine receptor agonists |
| BRPI0713902A2 (pt) * | 2006-06-27 | 2012-11-27 | Biovitrum Ab | compostos terapêuticos |
-
2007
- 2007-06-26 AU AU2007263728A patent/AU2007263728A1/en not_active Abandoned
- 2007-06-26 CA CA002654375A patent/CA2654375A1/en not_active Abandoned
- 2007-06-26 JP JP2009517175A patent/JP2009541438A/ja not_active Withdrawn
- 2007-06-26 NZ NZ573308A patent/NZ573308A/en not_active IP Right Cessation
- 2007-06-26 CN CNA2007800237458A patent/CN101479289A/zh active Pending
- 2007-06-26 US US11/823,377 patent/US7807685B2/en not_active Expired - Fee Related
- 2007-06-26 EP EP07786850A patent/EP2081946B1/en active Active
- 2007-06-26 WO PCT/EP2007/056378 patent/WO2008000745A2/en not_active Ceased
- 2007-06-26 RU RU2009102531/04A patent/RU2441875C2/ru not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ573308A (en) | 2012-02-24 |
| WO2008000745A2 (en) | 2008-01-03 |
| RU2009102531A (ru) | 2010-08-10 |
| JP2009541438A (ja) | 2009-11-26 |
| WO2008000745A3 (en) | 2008-04-17 |
| EP2081946B1 (en) | 2012-05-30 |
| EP2081946A2 (en) | 2009-07-29 |
| CA2654375A1 (en) | 2008-01-03 |
| RU2441875C2 (ru) | 2012-02-10 |
| US7807685B2 (en) | 2010-10-05 |
| US20080076776A1 (en) | 2008-03-27 |
| CN101479289A (zh) | 2009-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2005218997B2 (en) | Adenosine receptor agonists | |
| TWI620755B (zh) | 作為流感病毒ｒｎａ複製之抑制劑之經４’－二氟甲基取代之核苷衍生物 | |
| AU2007263728A1 (en) | Adenosine derivatives for the treatment of pain | |
| HUE033727T2 (en) | 2 ', 4'-difluoro-2'-methyl-substituted nucleoside derivatives as inhibitors of HCV RNA replication | |
| KR102573609B1 (ko) | 호흡기 세포융합 바이러스 rna 복제 억제제로서의 4'-비닐 치환된 뉴클레오시드 유도체 | |
| WO2016115222A1 (en) | 4'-azido substituted nucleoside derivatives as inhibitors of ebola virus rna replication | |
| US7906518B2 (en) | Therapeutic compounds | |
| US7820811B2 (en) | Pro-drugs of adenosine receptor agonists | |
| HK1129228A (en) | Therapeutic compounds | |
| TW202600819A (zh) | 新穎帽類似物及其使用方法 | |
| JP2020164521A (ja) | 抗ウィルス薬 | |
| NZ723551B2 (en) | 4'-difluoromethyl substituted nucleoside derivatives as inhibitors of influenza rna replication | |
| NZ549235A (en) | Adenosine receptor agonists | |
| 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 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |