JP2006526656A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2006526656A5 JP2006526656A5 JP2006515154A JP2006515154A JP2006526656A5 JP 2006526656 A5 JP2006526656 A5 JP 2006526656A5 JP 2006515154 A JP2006515154 A JP 2006515154A JP 2006515154 A JP2006515154 A JP 2006515154A JP 2006526656 A5 JP2006526656 A5 JP 2006526656A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- methyl
- aryl
- cycloalkyl
- 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.)
- Pending
Links
- -1 SO 3 R 7 Inorganic materials 0.000 claims description 187
- 125000000217 alkyl group Chemical group 0.000 claims description 157
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 124
- 125000003118 aryl group Chemical group 0.000 claims description 110
- 125000000623 heterocyclic group Chemical group 0.000 claims description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 52
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 37
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 25
- 125000000304 alkynyl group Chemical group 0.000 claims description 21
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 108090000695 Cytokines Proteins 0.000 claims description 5
- 102000004127 Cytokines Human genes 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- WTQSZUPMNGWJGE-UHFFFAOYSA-N n-benzyl-4-[4-(cyanomethyl)phenyl]-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(CC#N)=CC=2)=C1C(=O)NCC1=CC=CC=C1 WTQSZUPMNGWJGE-UHFFFAOYSA-N 0.000 claims description 3
- WPTHXTIVDNEWDS-UHFFFAOYSA-N n-methoxy-4-methyl-3-[(5-phenyl-1h-1,2,4-triazol-3-yl)amino]benzamide Chemical compound CONC(=O)C1=CC=C(C)C(NC=2NC(=NN=2)C=2C=CC=CC=2)=C1 WPTHXTIVDNEWDS-UHFFFAOYSA-N 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- 101000628954 Homo sapiens Mitogen-activated protein kinase 12 Proteins 0.000 claims description 2
- 102100026932 Mitogen-activated protein kinase 12 Human genes 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- OZTYUWVDJAFMQE-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(4-morpholin-4-ylphenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(=CC=2)N2CCOCC2)=C1C(=O)NCC1=CC=CC=C1 OZTYUWVDJAFMQE-UHFFFAOYSA-N 0.000 claims description 2
- QNQQSWPDHZLEEZ-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1)=NC=1C1=CC=CC=C1 QNQQSWPDHZLEEZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 59
- 125000005843 halogen group Chemical group 0.000 claims 46
- 125000001188 haloalkyl group Chemical group 0.000 claims 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 40
- 150000002431 hydrogen Chemical class 0.000 claims 40
- 125000000547 substituted alkyl group Chemical group 0.000 claims 38
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 32
- 229910052760 oxygen Inorganic materials 0.000 claims 32
- 229910052757 nitrogen Inorganic materials 0.000 claims 29
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 28
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 28
- 239000003795 chemical substances by application Substances 0.000 claims 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims 24
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 24
- 125000003545 alkoxy group Chemical group 0.000 claims 23
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 23
- 125000004043 oxo group Chemical group O=* 0.000 claims 23
- 201000010099 disease Diseases 0.000 claims 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 21
- 125000005236 alkanoylamino group Chemical group 0.000 claims 21
- 125000004414 alkyl thio group Chemical group 0.000 claims 21
- 125000001769 aryl amino group Chemical group 0.000 claims 21
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 21
- 229910052799 carbon Inorganic materials 0.000 claims 21
- 125000004438 haloalkoxy group Chemical group 0.000 claims 21
- 125000003107 substituted aryl group Chemical group 0.000 claims 21
- 229910052717 sulfur Inorganic materials 0.000 claims 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 19
- 125000005842 heteroatom Chemical group 0.000 claims 18
- 208000035475 disorder Diseases 0.000 claims 17
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 14
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 14
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims 14
- 125000004423 acyloxy group Chemical group 0.000 claims 14
- 125000003282 alkyl amino group Chemical group 0.000 claims 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 14
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims 14
- 125000004104 aryloxy group Chemical group 0.000 claims 14
- 125000001589 carboacyl group Chemical group 0.000 claims 14
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 14
- 229940124530 sulfonamide Drugs 0.000 claims 14
- 150000003456 sulfonamides Chemical class 0.000 claims 14
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 14
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 12
- 125000000335 thiazolyl group Chemical group 0.000 claims 12
- 239000003814 drug Substances 0.000 claims 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 10
- 229940079593 drug Drugs 0.000 claims 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 10
- 125000001544 thienyl group Chemical group 0.000 claims 9
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 8
- 125000002541 furyl group Chemical group 0.000 claims 8
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 8
- 125000002950 monocyclic group Chemical group 0.000 claims 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 8
- 125000004076 pyridyl group Chemical group 0.000 claims 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 8
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 7
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims 7
- 206010040070 Septic Shock Diseases 0.000 claims 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims 7
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims 7
- 125000005239 aroylamino group Chemical group 0.000 claims 7
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims 7
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims 7
- 125000005110 aryl thio group Chemical group 0.000 claims 7
- 229910052794 bromium Inorganic materials 0.000 claims 7
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 7
- 125000004432 carbon atom Chemical group C* 0.000 claims 7
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 7
- 229910052801 chlorine Inorganic materials 0.000 claims 7
- 125000004966 cyanoalkyl group Chemical group 0.000 claims 7
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims 7
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims 7
- 229910052731 fluorine Inorganic materials 0.000 claims 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 7
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 150000002367 halogens Chemical class 0.000 claims 7
- 125000002883 imidazolyl group Chemical group 0.000 claims 7
- 125000001041 indolyl group Chemical group 0.000 claims 7
- 208000015181 infectious disease Diseases 0.000 claims 7
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 7
- 238000006467 substitution reaction Methods 0.000 claims 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims 7
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 7
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims 6
- 201000008482 osteoarthritis Diseases 0.000 claims 5
- 230000000770 proinflammatory effect Effects 0.000 claims 5
- 102000004169 proteins and genes Human genes 0.000 claims 5
- 108090000623 proteins and genes Proteins 0.000 claims 5
- 208000020084 Bone disease Diseases 0.000 claims 4
- 206010006895 Cachexia Diseases 0.000 claims 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims 4
- 201000005569 Gout Diseases 0.000 claims 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 4
- 208000034578 Multiple myelomas Diseases 0.000 claims 4
- 208000002193 Pain Diseases 0.000 claims 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 4
- 206010037660 Pyrexia Diseases 0.000 claims 4
- 206010063837 Reperfusion injury Diseases 0.000 claims 4
- 206010040047 Sepsis Diseases 0.000 claims 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 4
- 208000036142 Viral infection Diseases 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 230000001939 inductive effect Effects 0.000 claims 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims 4
- 230000036407 pain Effects 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 4
- 208000024891 symptom Diseases 0.000 claims 4
- 230000009385 viral infection Effects 0.000 claims 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 3
- 208000011231 Crohn disease Diseases 0.000 claims 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims 3
- 108010002352 Interleukin-1 Proteins 0.000 claims 3
- 201000004681 Psoriasis Diseases 0.000 claims 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 3
- 206010044248 Toxic shock syndrome Diseases 0.000 claims 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 3
- 230000002917 arthritic effect Effects 0.000 claims 3
- 206010003246 arthritis Diseases 0.000 claims 3
- 208000006673 asthma Diseases 0.000 claims 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 208000027866 inflammatory disease Diseases 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- 230000004770 neurodegeneration Effects 0.000 claims 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 230000036303 septic shock Effects 0.000 claims 3
- 230000003612 virological effect Effects 0.000 claims 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- 208000030507 AIDS Diseases 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 206010055128 Autoimmune neutropenia Diseases 0.000 claims 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
- 208000023328 Basedow disease Diseases 0.000 claims 2
- 201000006474 Brain Ischemia Diseases 0.000 claims 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims 2
- 206010063094 Cerebral malaria Diseases 0.000 claims 2
- 206010008909 Chronic Hepatitis Diseases 0.000 claims 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 claims 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims 2
- 208000037487 Endotoxemia Diseases 0.000 claims 2
- 206010018634 Gouty Arthritis Diseases 0.000 claims 2
- 208000015023 Graves' disease Diseases 0.000 claims 2
- 208000031886 HIV Infections Diseases 0.000 claims 2
- 208000037357 HIV infectious disease Diseases 0.000 claims 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 2
- 208000005176 Hepatitis C Diseases 0.000 claims 2
- 206010019755 Hepatitis chronic active Diseases 0.000 claims 2
- 206010020751 Hypersensitivity Diseases 0.000 claims 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims 2
- 108090001007 Interleukin-8 Proteins 0.000 claims 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 2
- 206010027480 Metastatic malignant melanoma Diseases 0.000 claims 2
- 102000056248 Mitogen-activated protein kinase 13 Human genes 0.000 claims 2
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 claims 2
- 208000000112 Myalgia Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000001132 Osteoporosis Diseases 0.000 claims 2
- 206010033645 Pancreatitis Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims 2
- 102000001253 Protein Kinase Human genes 0.000 claims 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 2
- 208000033464 Reiter syndrome Diseases 0.000 claims 2
- 206010039710 Scleroderma Diseases 0.000 claims 2
- 201000010001 Silicosis Diseases 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 206010043781 Thyroiditis chronic Diseases 0.000 claims 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 231100000354 acute hepatitis Toxicity 0.000 claims 2
- 208000026935 allergic disease Diseases 0.000 claims 2
- 230000007815 allergy Effects 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 201000008937 atopic dermatitis Diseases 0.000 claims 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 2
- 208000019664 bone resorption disease Diseases 0.000 claims 2
- 206010008118 cerebral infarction Diseases 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 208000001763 cytomegalovirus retinitis Diseases 0.000 claims 2
- 230000001066 destructive effect Effects 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 208000001848 dysentery Diseases 0.000 claims 2
- 239000002158 endotoxin Substances 0.000 claims 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 2
- 208000006454 hepatitis Diseases 0.000 claims 2
- 208000005252 hepatitis A Diseases 0.000 claims 2
- 208000002672 hepatitis B Diseases 0.000 claims 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 2
- 230000028709 inflammatory response Effects 0.000 claims 2
- 206010022000 influenza Diseases 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 208000014674 injury Diseases 0.000 claims 2
- 208000011379 keloid formation Diseases 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 208000021039 metastatic melanoma Diseases 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 208000013465 muscle pain Diseases 0.000 claims 2
- 206010028417 myasthenia gravis Diseases 0.000 claims 2
- FVTLNLZIDGYJGR-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(4-fluoro-3-methylphenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(C)C(F)=CC=2)=C1C(=O)NCC1=CC=CC=C1 FVTLNLZIDGYJGR-UHFFFAOYSA-N 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000002062 proliferating effect Effects 0.000 claims 2
- 108060006633 protein kinase Proteins 0.000 claims 2
- 230000002685 pulmonary effect Effects 0.000 claims 2
- 208000002574 reactive arthritis Diseases 0.000 claims 2
- 201000005404 rubella Diseases 0.000 claims 2
- 231100000241 scar Toxicity 0.000 claims 2
- 201000004595 synovitis Diseases 0.000 claims 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 206010043554 thrombocytopenia Diseases 0.000 claims 2
- 230000009772 tissue formation Effects 0.000 claims 2
- 230000008733 trauma Effects 0.000 claims 2
- 201000008827 tuberculosis Diseases 0.000 claims 2
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical group C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical group C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical group C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
- NWUBXHJULBWGIM-UHFFFAOYSA-N 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxylic acid Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC1=NC=C(C(O)=O)S1 NWUBXHJULBWGIM-UHFFFAOYSA-N 0.000 claims 1
- OCGLEDQGYPNHDV-UHFFFAOYSA-N 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-n-(cyclopropylmethyl)-4-phenyl-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC=CC=2)=C1C(=O)NCC1CC1 OCGLEDQGYPNHDV-UHFFFAOYSA-N 0.000 claims 1
- IHRQWVMNOWRFCP-UHFFFAOYSA-N 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-n-phenyl-1,3-thiazole-4-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1)=NC=1C(=O)NC1=CC=CC=C1 IHRQWVMNOWRFCP-UHFFFAOYSA-N 0.000 claims 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims 1
- CNSPTSKZQDDULZ-UHFFFAOYSA-N 3-[[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1)=NC=1C1=CC=C(C#N)C=C1 CNSPTSKZQDDULZ-UHFFFAOYSA-N 0.000 claims 1
- XAFXTWJDDHQNPQ-UHFFFAOYSA-N 3-[[5-bromo-4-(4-nitrophenyl)-1,3-thiazol-2-yl]amino]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1Br)=NC=1C1=CC=C([N+]([O-])=O)C=C1 XAFXTWJDDHQNPQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- UXWAALAANHCMTJ-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yl)-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C3OCOC3=CC=2)=C1C(=O)NCC1=CC=CC=C1 UXWAALAANHCMTJ-UHFFFAOYSA-N 0.000 claims 1
- UAHXHYKIAMOYFJ-UHFFFAOYSA-N 4-(3-aminophenyl)-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(N)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 UAHXHYKIAMOYFJ-UHFFFAOYSA-N 0.000 claims 1
- OSJHWBWDVVSUEQ-UHFFFAOYSA-N 4-(4-aminophenyl)-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(N)=CC=2)=C1C(=O)NCC1=CC=CC=C1 OSJHWBWDVVSUEQ-UHFFFAOYSA-N 0.000 claims 1
- DFXXMUXBBCAHOG-UHFFFAOYSA-N 4-(5-acetylthiophen-2-yl)-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)C)=CC=C1C1=C(C(=O)NCC=2C=CC=CC=2)SC(NC=2C(=CC=C(C=2)C(=O)NC2CC2)C)=N1 DFXXMUXBBCAHOG-UHFFFAOYSA-N 0.000 claims 1
- YOLMLJJNQRQDSA-UHFFFAOYSA-N 4-[3-(aminomethyl)phenyl]-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(CN)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 YOLMLJJNQRQDSA-UHFFFAOYSA-N 0.000 claims 1
- ZHTUZCAHAPRBSM-UHFFFAOYSA-N 4-[3-[(2-aminoacetyl)amino]phenyl]-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(NC(=O)CN)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 ZHTUZCAHAPRBSM-UHFFFAOYSA-N 0.000 claims 1
- NPBNJCQOBAFZHD-UHFFFAOYSA-N 4-[4-(2-aminoethyl)phenyl]-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(CCN)=CC=2)=C1C(=O)NCC1=CC=CC=C1 NPBNJCQOBAFZHD-UHFFFAOYSA-N 0.000 claims 1
- XDHFZIKAZGVCPC-UHFFFAOYSA-N 4-[4-[(2-aminoacetyl)amino]phenyl]-n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(NC(=O)CN)=CC=2)=C1C(=O)NCC1=CC=CC=C1 XDHFZIKAZGVCPC-UHFFFAOYSA-N 0.000 claims 1
- IXYZLXGJXNBJRH-UHFFFAOYSA-N 4-[5-(benzylcarbamoyl)-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-1,3-thiazol-4-yl]benzoic acid Chemical compound CC1=CC=C(C2CC2)C=C1N(C(N)=O)C(S1)=NC(C=2C=CC(=CC=2)C(O)=O)=C1C(=O)NCC1=CC=CC=C1 IXYZLXGJXNBJRH-UHFFFAOYSA-N 0.000 claims 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 1
- PIFMFKSWUQYDJF-UHFFFAOYSA-N 4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]-n-(1,2,4-triazol-4-yl)benzamide Chemical compound CC1=CC=C(C(=O)NN2C=NN=C2)C=C1NC(SC=1)=NC=1C1=CC=CC=C1 PIFMFKSWUQYDJF-UHFFFAOYSA-N 0.000 claims 1
- SMQUKEWWJWEHIJ-UHFFFAOYSA-N 4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]-n-propan-2-ylbenzamide Chemical compound CC(C)NC(=O)C1=CC=C(C)C(NC=2SC=C(N=2)C=2C=CC=CC=2)=C1 SMQUKEWWJWEHIJ-UHFFFAOYSA-N 0.000 claims 1
- LHWHNRWSVMZQKC-UHFFFAOYSA-N 4-methyl-5-[(4-phenyl-1,3-thiazol-2-yl)amino]-1-(1,3-thiazol-2-yl)cyclohexa-2,4-diene-1-carboxamide Chemical compound C1=CC(C)=C(NC=2SC=C(N=2)C=2C=CC=CC=2)CC1(C(N)=O)C1=NC=CS1 LHWHNRWSVMZQKC-UHFFFAOYSA-N 0.000 claims 1
- OTAXXNTXLPMBGI-UHFFFAOYSA-N 4-methyl-n-(5-methyl-1,3,4-thiadiazol-2-yl)-3-[(4-phenyl-1,3-thiazol-2-yl)amino]benzamide Chemical compound S1C(C)=NN=C1NC(=O)C1=CC=C(C)C(NC=2SC=C(N=2)C=2C=CC=CC=2)=C1 OTAXXNTXLPMBGI-UHFFFAOYSA-N 0.000 claims 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 241000283707 Capra Species 0.000 claims 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims 1
- 208000006029 Cardiomegaly Diseases 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 208000000668 Chronic Pancreatitis Diseases 0.000 claims 1
- 241000713730 Equine infectious anemia virus Species 0.000 claims 1
- WZYOBNMXHJBLAO-UHFFFAOYSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.C(C1=CC=CC=C1)N Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.C(C1=CC=CC=C1)N WZYOBNMXHJBLAO-UHFFFAOYSA-N 0.000 claims 1
- LEDHDQUUWLADFP-UHFFFAOYSA-N FC(C(=O)[O-])(F)F.FC(C(=O)[O-])(F)F.C(C1=CC=CC=C1)NC(=O)C1=C(N=C(S1)NC1=C(C=CC(=C1)C(NC1CC1)=O)C)C1=CC=C(C=C1)NC(=O)CC[NH3+].C(C1=CC=CC=C1)NC(=O)C1=C(N=C(S1)NC1=C(C=CC(=C1)C(NC1CC1)=O)C)C1=CC=C(C=C1)NC(=O)CC[NH3+] Chemical compound FC(C(=O)[O-])(F)F.FC(C(=O)[O-])(F)F.C(C1=CC=CC=C1)NC(=O)C1=C(N=C(S1)NC1=C(C=CC(=C1)C(NC1CC1)=O)C)C1=CC=C(C=C1)NC(=O)CC[NH3+].C(C1=CC=CC=C1)NC(=O)C1=C(N=C(S1)NC1=C(C=CC(=C1)C(NC1CC1)=O)C)C1=CC=C(C=C1)NC(=O)CC[NH3+] LEDHDQUUWLADFP-UHFFFAOYSA-N 0.000 claims 1
- 208000007882 Gastritis Diseases 0.000 claims 1
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 1
- 206010019233 Headaches Diseases 0.000 claims 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims 1
- 108090001005 Interleukin-6 Proteins 0.000 claims 1
- 241001024304 Mino Species 0.000 claims 1
- 206010028289 Muscle atrophy Diseases 0.000 claims 1
- 206010029113 Neovascularisation Diseases 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 claims 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 1
- 206010033647 Pancreatitis acute Diseases 0.000 claims 1
- 206010033649 Pancreatitis chronic Diseases 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 208000005074 Retroviridae Infections Diseases 0.000 claims 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 claims 1
- 206010048873 Traumatic arthritis Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 241000713325 Visna/maedi virus Species 0.000 claims 1
- RRHCEJCTEIGQNA-UHFFFAOYSA-N [4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]phenyl]-morpholin-4-ylmethanone Chemical compound CC1=CC=C(C(=O)N2CCOCC2)C=C1NC(SC=1)=NC=1C1=CC=CC=C1 RRHCEJCTEIGQNA-UHFFFAOYSA-N 0.000 claims 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 201000003229 acute pancreatitis Diseases 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
- 230000036592 analgesia Effects 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000002491 angiogenic effect Effects 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 201000005000 autoimmune gastritis Diseases 0.000 claims 1
- 230000005784 autoimmunity Effects 0.000 claims 1
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims 1
- ZLSQYHQYXIKMMJ-UHFFFAOYSA-N benzyl 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-methyl-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OCC=2C=CC=CC=2)=C(C)N=C1NC(C(=CC=1)C)=CC=1C(=O)NC1CC1 ZLSQYHQYXIKMMJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004799 bromophenyl group Chemical group 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- QGQIETIGUVGVPB-UHFFFAOYSA-N ethyl 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC=2C(=CC=C(C=2)C(=O)NC2CC2)C)=N1 QGQIETIGUVGVPB-UHFFFAOYSA-N 0.000 claims 1
- JGENTJZJQZMUFR-UHFFFAOYSA-N ethyl 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(4-nitrophenyl)-1,3-thiazole-5-carboxylate Chemical compound N=1C(C=2C=CC(=CC=2)[N+]([O-])=O)=C(C(=O)OCC)SC=1NC(C(=CC=1)C)=CC=1C(=O)NC1CC1 JGENTJZJQZMUFR-UHFFFAOYSA-N 0.000 claims 1
- UHJFBWBTTZAVLT-UHFFFAOYSA-N ethyl 5-bromo-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-4-carboxylate Chemical compound S1C(Br)=C(C(=O)OCC)N=C1NC1=CC(C(=O)NC2CC2)=CC=C1C UHJFBWBTTZAVLT-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims 1
- 208000024908 graft versus host disease Diseases 0.000 claims 1
- 231100000869 headache Toxicity 0.000 claims 1
- 201000011066 hemangioma Diseases 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 230000008595 infiltration Effects 0.000 claims 1
- 238000001764 infiltration Methods 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- DBRHDNJPOIUCQG-UHFFFAOYSA-N methyl 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OC)=CN=C1NC1=CC(C(=O)NC2CC2)=CC=C1C DBRHDNJPOIUCQG-UHFFFAOYSA-N 0.000 claims 1
- IYQVONCDQGPIHR-UHFFFAOYSA-N methyl 2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-[3-(1-methoxycarbonylpiperidin-4-yl)phenyl]-1,3-thiazole-5-carboxylate Chemical compound C1CN(C(=O)OC)CCC1C1=CC=CC(C2=C(SC(NC=3C(=CC=C(C=3)C(=O)NC3CC3)C)=N2)C(=O)OC)=C1 IYQVONCDQGPIHR-UHFFFAOYSA-N 0.000 claims 1
- WOHLTZKNMPFWJT-UHFFFAOYSA-N methyl 4-[3-[2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-5-(cyclopropylmethylcarbamoyl)-1,3-thiazol-4-yl]phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1C1=CC=CC(C2=C(SC(NC=3C(=CC=C(C=3)C(=O)NC3CC3)C)=N2)C(=O)NCC2CC2)=C1 WOHLTZKNMPFWJT-UHFFFAOYSA-N 0.000 claims 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- UDGWQRMNULDRJR-UHFFFAOYSA-N n-(2-methoxyethyl)-4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]benzamide Chemical compound COCCNC(=O)C1=CC=C(C)C(NC=2SC=C(N=2)C=2C=CC=CC=2)=C1 UDGWQRMNULDRJR-UHFFFAOYSA-N 0.000 claims 1
- DBCALFNQCPBAJI-UHFFFAOYSA-N n-benzyl-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-4-(2-chlorophenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C2CC2)C=C1N(C(N)=O)C(S1)=NC(C=2C(=CC=CC=2)Cl)=C1C(=O)NCC1=CC=CC=C1 DBCALFNQCPBAJI-UHFFFAOYSA-N 0.000 claims 1
- BQQGRBVTXBZCNJ-UHFFFAOYSA-N n-benzyl-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-4-(2-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound COC1=CC=CC=C1C1=C(C(=O)NCC=2C=CC=CC=2)SC(N(C(N)=O)C=2C(=CC=C(C=2)C2CC2)C)=N1 BQQGRBVTXBZCNJ-UHFFFAOYSA-N 0.000 claims 1
- JQQMYJAZBWYKNA-UHFFFAOYSA-N n-benzyl-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-4-(3-cyanophenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C2CC2)C=C1N(C(N)=O)C(S1)=NC(C=2C=C(C=CC=2)C#N)=C1C(=O)NCC1=CC=CC=C1 JQQMYJAZBWYKNA-UHFFFAOYSA-N 0.000 claims 1
- YCQAVDQBBIFHNB-UHFFFAOYSA-N n-benzyl-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-4-(4-cyanophenyl)-4,5-dihydro-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C2CC2)C=C1N(C(N)=O)C(S1)=NC(C=2C=CC(=CC=2)C#N)C1C(=O)NCC1=CC=CC=C1 YCQAVDQBBIFHNB-UHFFFAOYSA-N 0.000 claims 1
- XMIVODSJIUOPDA-UHFFFAOYSA-N n-benzyl-2-(n-carbamoyl-5-cyclopropyl-2-methylanilino)-4-(4-fluorophenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C2CC2)C=C1N(C(N)=O)C(S1)=NC(C=2C=CC(F)=CC=2)=C1C(=O)NCC1=CC=CC=C1 XMIVODSJIUOPDA-UHFFFAOYSA-N 0.000 claims 1
- IPYLLIQRFOGOGL-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C3OCCOC3=CC=2)=C1C(=O)NCC1=CC=CC=C1 IPYLLIQRFOGOGL-UHFFFAOYSA-N 0.000 claims 1
- AFVBTXCAPIOLRT-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(3-methylphenyl)-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=CC(C2=C(SC(NC=3C(=CC=C(C=3)C(=O)NC3CC3)C)=N2)C(=O)NCC=2C=CC=CC=2)=C1 AFVBTXCAPIOLRT-UHFFFAOYSA-N 0.000 claims 1
- GJEJTLILMAVAPI-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-(4-methylphenyl)-1,3-thiazole-5-carboxamide Chemical compound C1=CC(C)=CC=C1C1=C(C(=O)NCC=2C=CC=CC=2)SC(NC=2C(=CC=C(C=2)C(=O)NC2CC2)C)=N1 GJEJTLILMAVAPI-UHFFFAOYSA-N 0.000 claims 1
- SYLAUKXUQLHNPM-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-[3-(2-morpholin-4-ylethoxy)phenyl]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(OCCN3CCOCC3)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 SYLAUKXUQLHNPM-UHFFFAOYSA-N 0.000 claims 1
- BSMBCSPWKKJOGK-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-[3-(cyclopropylcarbamoyl)phenyl]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(C=CC=2)C(=O)NC2CC2)=C1C(=O)NCC1=CC=CC=C1 BSMBCSPWKKJOGK-UHFFFAOYSA-N 0.000 claims 1
- JSGPALWPYSFEES-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-[3-(methanesulfonamido)phenyl]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(NS(C)(=O)=O)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 JSGPALWPYSFEES-UHFFFAOYSA-N 0.000 claims 1
- WSVVHEDHBOCHBY-UHFFFAOYSA-N n-benzyl-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-4-methyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)NCC=2C=CC=CC=2)=C(C)N=C1NC(C(=CC=1)C)=CC=1C(=O)NC1CC1 WSVVHEDHBOCHBY-UHFFFAOYSA-N 0.000 claims 1
- BMJGGQAMNZIORE-UHFFFAOYSA-N n-benzyl-4-(4-carbamoylphenyl)-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(=CC=2)C(N)=O)=C1C(=O)NCC1=CC=CC=C1 BMJGGQAMNZIORE-UHFFFAOYSA-N 0.000 claims 1
- JMLVNPDFPGNFSV-UHFFFAOYSA-N n-benzyl-4-(5-cyanothiophen-2-yl)-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1C(=O)NCC=2C=CC=CC=2)=NC=1C1=CC=C(C#N)S1 JMLVNPDFPGNFSV-UHFFFAOYSA-N 0.000 claims 1
- UFUAXYLDRGEYMT-UHFFFAOYSA-N n-benzyl-4-bromo-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazole-5-carboxamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(Br)=C1C(=O)NCC1=CC=CC=C1 UFUAXYLDRGEYMT-UHFFFAOYSA-N 0.000 claims 1
- DUKISKBCIROUAU-UHFFFAOYSA-N n-cyclopropyl-3-[[4-(2-methoxyphenyl)-1,3-thiazol-2-yl]amino]-4-methylbenzamide Chemical compound COC1=CC=CC=C1C1=CSC(NC=2C(=CC=C(C=2)C(=O)NC2CC2)C)=N1 DUKISKBCIROUAU-UHFFFAOYSA-N 0.000 claims 1
- GZBCKDMCPDQECD-UHFFFAOYSA-N n-cyclopropyl-3-[[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]amino]-4-methylbenzamide Chemical compound COC1=CC=CC(C=2N=C(NC=3C(=CC=C(C=3)C(=O)NC3CC3)C)SC=2)=C1 GZBCKDMCPDQECD-UHFFFAOYSA-N 0.000 claims 1
- BVMJHLWOIQRDDZ-UHFFFAOYSA-N n-cyclopropyl-3-[[4-(4-fluorophenyl)-1,3-thiazol-2-yl]amino]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1)=NC=1C1=CC=C(F)C=C1 BVMJHLWOIQRDDZ-UHFFFAOYSA-N 0.000 claims 1
- SMLHKPSWOLMYRM-UHFFFAOYSA-N n-cyclopropyl-3-[[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]amino]-4-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C1=CSC(NC=2C(=CC=C(C=2)C(=O)NC2CC2)C)=N1 SMLHKPSWOLMYRM-UHFFFAOYSA-N 0.000 claims 1
- QWNXYSNYDKBHKX-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(3-phenyl-1,2,4-thiadiazol-5-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SN=1)=NC=1C1=CC=CC=C1 QWNXYSNYDKBHKX-UHFFFAOYSA-N 0.000 claims 1
- BOGVGVABAWLPGV-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(5-methyl-4-phenyl-1,3-thiazol-2-yl)amino]benzamide Chemical compound N=1C(C=2C=CC=CC=2)=C(C)SC=1NC(C(=CC=1)C)=CC=1C(=O)NC1CC1 BOGVGVABAWLPGV-UHFFFAOYSA-N 0.000 claims 1
- NUFPZYCKOZSPTH-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NN=C1C1=CC=CC=C1 NUFPZYCKOZSPTH-UHFFFAOYSA-N 0.000 claims 1
- CKPWPYNTFBAPMP-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(5-phenyl-1,3-oxazol-2-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(O1)=NC=C1C1=CC=CC=C1 CKPWPYNTFBAPMP-UHFFFAOYSA-N 0.000 claims 1
- VIQABIAQWAZJLM-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[(5-phenyl-1h-1,2,4-triazol-3-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(N1)=NN=C1C1=CC=CC=C1 VIQABIAQWAZJLM-UHFFFAOYSA-N 0.000 claims 1
- XRHBQUYAZDHOPT-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-[[4-(4-nitrophenyl)-1,3-thiazol-2-yl]amino]benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(SC=1)=NC=1C1=CC=C([N+]([O-])=O)C=C1 XRHBQUYAZDHOPT-UHFFFAOYSA-N 0.000 claims 1
- DTSHHFQPWUBYJW-UHFFFAOYSA-N n-ethyl-4-methyl-3-[(4-phenyl-1,3-thiazol-2-yl)amino]benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(NC=2SC=C(N=2)C=2C=CC=CC=2)=C1 DTSHHFQPWUBYJW-UHFFFAOYSA-N 0.000 claims 1
- 230000002232 neuromuscular Effects 0.000 claims 1
- 210000000440 neutrophil Anatomy 0.000 claims 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 150000003180 prostaglandins Chemical class 0.000 claims 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 1
- 230000004044 response Effects 0.000 claims 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- SAIMXMFQIANODG-UHFFFAOYSA-N tert-butyl n-[3-[3-[5-(benzylcarbamoyl)-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazol-4-yl]anilino]-3-oxopropyl]carbamate Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=C(NC(=O)CCNC(=O)OC(C)(C)C)C=CC=2)=C1C(=O)NCC1=CC=CC=C1 SAIMXMFQIANODG-UHFFFAOYSA-N 0.000 claims 1
- IKZXPLLEPRQRJB-UHFFFAOYSA-N tert-butyl n-[3-[4-[5-(benzylcarbamoyl)-2-[5-(cyclopropylcarbamoyl)-2-methylanilino]-1,3-thiazol-4-yl]anilino]-3-oxopropyl]carbamate Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1NC(S1)=NC(C=2C=CC(NC(=O)CCNC(=O)OC(C)(C)C)=CC=2)=C1C(=O)NCC1=CC=CC=C1 IKZXPLLEPRQRJB-UHFFFAOYSA-N 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 229960004072 thrombin Drugs 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 208000004371 toothache Diseases 0.000 claims 1
- 125000004306 triazinyl group Chemical group 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
- 231100000397 ulcer Toxicity 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 150000003852 triazoles Chemical class 0.000 description 3
- XWESVPXIDGLPNX-UHFFFAOYSA-N 1,2,4-oxadiazol-3-amine Chemical class NC=1N=CON=1 XWESVPXIDGLPNX-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- WJUKOGPNGRUXMG-UHFFFAOYSA-N 1,2-dibromo-1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)(Br)C(Cl)(Cl)Br WJUKOGPNGRUXMG-UHFFFAOYSA-N 0.000 description 1
- APKZPKINPXTSNL-UHFFFAOYSA-N 1,3,4-oxadiazol-2-amine Chemical class NC1=NN=CO1 APKZPKINPXTSNL-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- KXMMNJQMGILZDB-UHFFFAOYSA-N 1-(2-oxopyridine-1-carbothioyl)pyridin-2-one Chemical compound O=C1C=CC=CN1C(=S)N1C(=O)C=CC=C1 KXMMNJQMGILZDB-UHFFFAOYSA-N 0.000 description 1
- AKQWEDMTPCAESO-UHFFFAOYSA-N 1-(4-morpholin-4-ylphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1N1CCOCC1 AKQWEDMTPCAESO-UHFFFAOYSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- DBARIDXQZQWKGB-UHFFFAOYSA-N 3-(benzoylcarbamothioylamino)-n-methoxy-4-methylbenzamide Chemical compound CONC(=O)C1=CC=C(C)C(NC(=S)NC(=O)C=2C=CC=CC=2)=C1 DBARIDXQZQWKGB-UHFFFAOYSA-N 0.000 description 1
- XKFIFYROMAAUDL-UHFFFAOYSA-N 3-amino-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N XKFIFYROMAAUDL-UHFFFAOYSA-N 0.000 description 1
- NLESBTVHGWTLOM-UHFFFAOYSA-N 3-amino-n-cyclopropyl-4-methylbenzamide Chemical compound C1=C(N)C(C)=CC=C1C(=O)NC1CC1 NLESBTVHGWTLOM-UHFFFAOYSA-N 0.000 description 1
- SQIYHQDCDNQPPX-UHFFFAOYSA-N 3-amino-n-methoxy-4-methylbenzamide Chemical compound CONC(=O)C1=CC=C(C)C(N)=C1 SQIYHQDCDNQPPX-UHFFFAOYSA-N 0.000 description 1
- QRZMXADUXZADTF-UHFFFAOYSA-N 4-aminoimidazole Chemical compound NC1=CNC=N1 QRZMXADUXZADTF-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 0 Cc1ccc(*C2CC2)cc1Nc1nc(*)c(**)[s]1 Chemical compound Cc1ccc(*C2CC2)cc1Nc1nc(*)c(**)[s]1 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
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 101000919320 Homo sapiens Adapter molecule crk Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- YKVMTTIYBSVPEQ-UHFFFAOYSA-N [4-(cyanomethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(CC#N)C=C1 YKVMTTIYBSVPEQ-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229950003476 aminothiazole Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960000510 ammonia Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 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
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000002373 hemiacetals Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical group 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- ZIPLUEXSCPLCEI-UHFFFAOYSA-N iminomethylideneazanide Chemical compound [NH-]C#N ZIPLUEXSCPLCEI-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 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
- VQVWYKRGIMWUQU-UHFFFAOYSA-N n-benzyl-3-(4-morpholin-4-ylphenyl)-3-oxopropanamide Chemical compound C=1C=CC=CC=1CNC(=O)CC(=O)C(C=C1)=CC=C1N1CCOCC1 VQVWYKRGIMWUQU-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 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
- 238000002953 preparative HPLC Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47566203P | 2003-06-03 | 2003-06-03 | |
| US53154103P | 2003-12-19 | 2003-12-19 | |
| PCT/US2004/017580 WO2005000298A2 (en) | 2003-06-03 | 2004-06-02 | 5-membered heterocycle-based p-38 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006526656A JP2006526656A (ja) | 2006-11-24 |
| JP2006526656A5 true JP2006526656A5 (enExample) | 2007-08-16 |
Family
ID=33555395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006515154A Pending JP2006526656A (ja) | 2003-06-03 | 2004-06-02 | ５員ヘテロ環ベースのｐ−３８阻害剤 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7652044B2 (enExample) |
| EP (1) | EP1635824B1 (enExample) |
| JP (1) | JP2006526656A (enExample) |
| AT (1) | ATE439837T1 (enExample) |
| AU (1) | AU2004251668B2 (enExample) |
| BR (1) | BRPI0410905A (enExample) |
| CA (1) | CA2528438A1 (enExample) |
| DE (1) | DE602004022668D1 (enExample) |
| ES (1) | ES2332135T3 (enExample) |
| MX (1) | MXPA05013075A (enExample) |
| PL (1) | PL1635824T3 (enExample) |
| PT (1) | PT1635824E (enExample) |
| WO (1) | WO2005000298A2 (enExample) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3836019B2 (ja) * | 2001-11-21 | 2006-10-18 | 松下電器産業株式会社 | 受信装置、送信装置及び送信方法 |
| EP1585572A4 (en) | 2002-09-20 | 2010-02-24 | Flowmedica Inc | METHOD AND APPARATUS FOR ADMINISTERING INTRA-AORTIC SUBSTANCE TO A BRANCHED VESSEL |
| AU2003276903A1 (en) | 2002-09-20 | 2004-05-04 | Flowmedica, Inc. | Method and apparatus for selective material delivery via an intra-renal catheter |
| EP1635736A2 (en) | 2003-06-05 | 2006-03-22 | FlowMedica, Inc. | Systems and methods for performing bi-lateral interventions or diagnosis in branched body lumens |
| ATE465731T1 (de) * | 2003-10-23 | 2010-05-15 | Ab Science | 2-aminoaryloxazol-verbindungen als tyrosinkinase- hemmer |
| CN1934107A (zh) * | 2004-01-30 | 2007-03-21 | Ab科学公司 | 作为酪氨酸激酶抑制剂的2－(3－取代芳基)氨基－4－芳基－噻唑 |
| WO2005091910A2 (en) | 2004-03-04 | 2005-10-06 | Flowmedica, Inc. | Sheath for use in peripheral interventions |
| CN1972937A (zh) * | 2004-04-30 | 2007-05-30 | 先灵公司 | 神经肽受体调节剂 |
| WO2005112980A2 (en) * | 2004-05-14 | 2005-12-01 | Flowmedica, Inc. | Bi-lateral local renal delivery for treating congestive heart failure and for bnp therapy |
| MX2007012392A (es) * | 2005-04-04 | 2007-12-05 | Ab Science | Derivados de oxazol sustituidos y su uso como inhibidores de tirosina cinasa. |
| AU2006244203B2 (en) | 2005-05-09 | 2012-05-03 | Achillion Pharmaceuticals, Inc. | Thiazole compounds and methods of use |
| EP1904065A2 (en) * | 2005-07-14 | 2008-04-02 | AB Science | Use of dual c-kit/fgfr3 inhibitors for treating multiple myeloma |
| AU2006290814B2 (en) | 2005-09-13 | 2012-06-07 | Janssen Pharmaceutica N.V. | 2-aniline-4-aryl substituted thiazole derivatives |
| WO2007076460A2 (en) * | 2005-12-23 | 2007-07-05 | Kalypsys, Inc. | Substituted thiazole ureas useful as inhibitors of protein kinases |
| WO2007138110A2 (en) * | 2006-06-01 | 2007-12-06 | Devgen N.V. | Compounds that interact with ion channels, in particular with ion channels from the kv family |
| US7771401B2 (en) | 2006-06-08 | 2010-08-10 | Angiodynamics, Inc. | Selective renal cannulation and infusion systems and methods |
| US20080221551A1 (en) * | 2007-03-09 | 2008-09-11 | Flowmedica, Inc. | Acute kidney injury treatment systems and methods |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| WO2008150516A1 (en) * | 2007-06-04 | 2008-12-11 | The Trustees Of The University Of Pennsylvania | A method for testing and screening p38 map kinase modifiers |
| JO2784B1 (en) * | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| JP2011500625A (ja) * | 2007-10-18 | 2011-01-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | トリ置換された１，２，４−トリアゾール |
| US7632868B2 (en) * | 2007-10-31 | 2009-12-15 | Meta Cosmetics, Llc | Prostaglandin analog compositions to treat epithelial-related conditions |
| US20100074857A1 (en) * | 2008-09-23 | 2010-03-25 | Pamela Lipkin | Compositions and methods to treat epithelial-related conditions |
| AR070936A1 (es) * | 2008-03-19 | 2010-05-12 | Janssen Pharmaceutica Nv | 1,2,4 -triazoles trisustituidos |
| JP5486591B2 (ja) * | 2008-05-09 | 2014-05-07 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | アセチルコリン受容体モジュレーターとしての三置換ピラゾール |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| EP2560488B1 (en) | 2010-04-23 | 2015-10-28 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| US8759380B2 (en) | 2011-04-22 | 2014-06-24 | Cytokinetics, Inc. | Certain heterocycles, compositions thereof, and methods for their use |
| EP2869897A4 (en) | 2012-07-06 | 2016-09-28 | Univ Duke | ACTIVATION OF THE TRPV4 ION CHANNEL BY PHYSICAL STIMULI AND IMPORTANT ROLE FOR TRPV4 IN ORGANIC INFLAMMATION AND JUCKREIZ |
| WO2014181287A1 (en) * | 2013-05-09 | 2014-11-13 | Piramal Enterprises Limited | Heterocyclyl compounds and uses thereof |
| US9453002B2 (en) | 2013-08-16 | 2016-09-27 | Janssen Pharmaceutica Nv | Substituted imidazoles as N-type calcium channel blockers |
| WO2016028325A1 (en) | 2014-08-22 | 2016-02-25 | Duke University | Trpa1 and trpv4 inhibitors and methods of using the same for organ-specific inflammation and itch |
| US11229628B2 (en) | 2015-01-09 | 2022-01-25 | Duke University | TRPA1 and TRPV4 inhibitors and methods of using the same for organ-specific inflammation and itch |
| WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
| CA2996281C (en) * | 2015-08-31 | 2022-03-08 | Regents Of The University Of Minnesota | Opioid receptor modulators and use thereof |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
| CN109310683A (zh) | 2016-04-07 | 2019-02-05 | 杜克大学 | 用于消毒和麻醉的trpv4和trpa1的小分子双重抑制剂 |
| EP3388430A1 (en) | 2017-04-10 | 2018-10-17 | Technische Universität München | Compound, compound for use in the treatment of a pathological condition, a pharmaceutical composition and a method for preparing said compound |
| US12636290B2 (en) | 2018-12-20 | 2026-05-26 | Saint Louis University | BET inhibitors for modulating DUX4 expression in FSHD |
| PH12022551379A1 (en) | 2019-12-06 | 2023-05-03 | Vertex Pharma | Substituted tetrahydrofurans as modulators of sodium channels |
| WO2022147694A1 (en) * | 2021-01-06 | 2022-07-14 | Beijing Erai Therapeutics Co., Ltd. | Aminoheteroaryl compounds and uses thereof |
| SI4347031T1 (sl) | 2021-06-04 | 2026-01-30 | Vertex Pharmaceuticals Incorporated | N-(hidroksialkil (hetero)aril) tetrahidrofuran karboksamidi kot modulatorji natrijevih kanalčkov |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
| US4044126A (en) | 1972-04-20 | 1977-08-23 | Allen & Hanburys Limited | Steroidal aerosol compositions and process for the preparation thereof |
| GB1429184A (en) | 1972-04-20 | 1976-03-24 | Allen & Hanburys Ltd | Physically anti-inflammatory steroids for use in aerosols |
| USRE28819E (en) | 1972-12-08 | 1976-05-18 | Syntex (U.S.A.) Inc. | Dialkylated glycol compositions and medicament preparations containing same |
| US4200750A (en) | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| US4410545A (en) | 1981-02-13 | 1983-10-18 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
| US4328245A (en) | 1981-02-13 | 1982-05-04 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
| US4358603A (en) | 1981-04-16 | 1982-11-09 | Syntex (U.S.A.) Inc. | Acetal stabilized prostaglandin compositions |
| US4409239A (en) | 1982-01-21 | 1983-10-11 | Syntex (U.S.A.) Inc. | Propylene glycol diester solutions of PGE-type compounds |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
| US5033252A (en) | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| US5514643A (en) | 1993-08-16 | 1996-05-07 | Lucky Ltd. | 2-aminothiazolecarboxamide derivatives, processes for preparing the same and use thereof for controlling phytopathogenic organisms |
| CA2163399A1 (en) | 1994-11-24 | 1996-05-25 | Katsuhiro Kawano | Triazine derivative, chymase activity inhibitor and nitric oxide production inhibitor |
| IL118544A (en) | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| US5756499A (en) | 1996-01-11 | 1998-05-26 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| DK0891325T3 (da) * | 1996-03-29 | 2002-05-21 | Searle & Co | Para-substituerede phenylpropansyrederivater som integrinantagonister |
| US6147080A (en) | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US5945418A (en) | 1996-12-18 | 1999-08-31 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| JPH10237028A (ja) * | 1996-12-24 | 1998-09-08 | Chugai Pharmaceut Co Ltd | Ｎｏｓ阻害作用を有する芳香族アミン誘導体 |
| US5932576A (en) | 1997-05-22 | 1999-08-03 | G. D. Searle & Company | 3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors |
| US6087496A (en) | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| US6251914B1 (en) | 1997-07-02 | 2001-06-26 | Smithkline Beecham Corporation | Cycloalkyl substituted imidazoles |
| CN1158269C (zh) | 1997-10-27 | 2004-07-21 | 阿古龙制药公司 | 作为cdk抑制剂的取代的4-氨基-噻唑-2-基化合物 |
| US6130235A (en) | 1998-05-22 | 2000-10-10 | Scios Inc. | Compounds and methods to treat cardiac failure and other disorders |
| CA2342251A1 (en) | 1998-08-28 | 2000-03-09 | Scios Inc. | Use of piperidines and/or piperazines as inhibitors of p38-alpha kinase |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| AU762245B2 (en) * | 1998-09-18 | 2003-06-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| AU764479B2 (en) | 1998-10-29 | 2003-08-21 | Bristol-Myers Squibb Company | Compounds derived from an amine nucleus that are inhibitors of IMPDH enzyme |
| GB9906566D0 (en) | 1999-03-23 | 1999-05-19 | Zeneca Ltd | Chemical compounds |
| CA2366932C (en) | 1999-04-15 | 2009-08-25 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| GB9924092D0 (en) | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
| US6610697B1 (en) | 1999-11-10 | 2003-08-26 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted 2-aryl-3-(heteroaryl)-imidazo[1,2-a]pyrimidines, and related pharmaceutical compositions and methods |
| WO2001056567A1 (en) | 2000-02-04 | 2001-08-09 | Novo Nordisk A/S | 2,4-diaminothiazole derivatives and their use as glycogen synthase kinase-3 (gsk-3) inhibitors |
| AU2001249670A1 (en) * | 2000-04-03 | 2001-10-15 | 3-Dimensional Pharmaceuticals, Inc. | Substituted thiazoles and the use thereof as inhibitors of plasminogen activatorinhibitor-1 |
| WO2002024200A1 (en) | 2000-09-21 | 2002-03-28 | Bristol-Myers Squibb Company | Substituted azole derivatives as inhibitors of corticotropin releasing factor |
| AU3276002A (en) | 2000-11-17 | 2002-05-27 | Bristol Myers Squibb Co | Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors |
| US6756374B2 (en) | 2001-01-22 | 2004-06-29 | Hoffmann-La Roche Inc. | Diaminothiazoles having antiproliferative activity |
| GB0104050D0 (en) * | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| AU2002316421B2 (en) * | 2001-06-26 | 2008-05-15 | Bristol-Myers Squibb Company | N-heterocyclic inhibitors of TNF-ALPHA expression |
| HN2002000156A (es) * | 2001-07-06 | 2003-11-27 | Inc Agouron Pharmaceuticals | Derivados de benzamida tiazol y composiciones farmaceuticas para inhibir la proliferacion de celulas y metodos para su utilización. |
| GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124928D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124936D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124931D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124932D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0217757D0 (en) | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| WO2004072068A1 (en) * | 2003-02-10 | 2004-08-26 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| ATE465731T1 (de) * | 2003-10-23 | 2010-05-15 | Ab Science | 2-aminoaryloxazol-verbindungen als tyrosinkinase- hemmer |
-
2004
- 2004-06-02 MX MXPA05013075A patent/MXPA05013075A/es active IP Right Grant
- 2004-06-02 EP EP04754233A patent/EP1635824B1/en not_active Expired - Lifetime
- 2004-06-02 PT PT04754233T patent/PT1635824E/pt unknown
- 2004-06-02 AT AT04754233T patent/ATE439837T1/de not_active IP Right Cessation
- 2004-06-02 ES ES04754233T patent/ES2332135T3/es not_active Expired - Lifetime
- 2004-06-02 DE DE602004022668T patent/DE602004022668D1/de not_active Expired - Lifetime
- 2004-06-02 AU AU2004251668A patent/AU2004251668B2/en not_active Ceased
- 2004-06-02 PL PL04754233T patent/PL1635824T3/pl unknown
- 2004-06-02 WO PCT/US2004/017580 patent/WO2005000298A2/en not_active Ceased
- 2004-06-02 US US10/860,768 patent/US7652044B2/en not_active Expired - Fee Related
- 2004-06-02 BR BRPI0410905-8A patent/BRPI0410905A/pt not_active IP Right Cessation
- 2004-06-02 JP JP2006515154A patent/JP2006526656A/ja active Pending
- 2004-06-02 CA CA002528438A patent/CA2528438A1/en not_active Abandoned
-
2009
- 2009-09-11 US US12/557,835 patent/US20100004298A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004251668B2 (en) | 5-membered heterocycle-based p-38 inhibitors | |
| TWI406862B (zh) | 合成作為激酶抑制劑之２-胺基噻唑化合物的方法 | |
| EP2468717B1 (en) | Heterocyclic Amide Compounds Useful as Kinase Inhibitors | |
| JP5290524B2 (ja) | チアゾール誘導体およびその使用 | |
| AU2001266345B2 (en) | Five-membered-ring compound | |
| JPWO2000004014A1 (ja) | 抗腫瘍活性を有するピリミジン誘導体 | |
| CA2568766A1 (en) | Crth2 receptor ligands for medicinal uses | |
| CA2396824A1 (en) | Heteroaromatic carboxamide derivatives and their use as inhibitors of the enzyme ikk-2 | |
| JP2009524670A5 (enExample) | ||
| JP2010513283A5 (enExample) | ||
| US20040142985A1 (en) | Heterocyclic compounds useful to treat HCV | |
| CA2716320A1 (en) | Selective androgen receptor modulators | |
| JP2002506858A (ja) | Ｃｍｖ感染症の治療に有用な１，３，４−チアジアゾール | |
| MX2013008718A (es) | Inhibicion de il17 e ifn-gamma para tratamiento de inflamacion autoinmune. | |
| MX2013008722A (es) | Inhibicion del il17 e ifn-gamma para el tratamiento de inflamacion autoinmune. | |
| JPWO2002002542A1 (ja) | ５員環化合物 | |
| JP2012505260A (ja) | 新規な２−アミドチアジアゾール誘導体 | |
| ES2220504T3 (es) | Derivados del aminotiazol y su uso como ligandos receptores de crf. | |
| JP2014513122A5 (enExample) | ||
| KR20080034436A (ko) | 암 치료에 사용되는 티아졸 유도체 및 유사체 | |
| CA2260263A1 (en) | Novel thiophene derivative and pharmaceutical composition thereof | |
| MXPA06005736A (es) | Compuestos de quinazolinona con bioacumulacion reducida. | |
| JP2004509863A (ja) | コルチコトロピン放出因子のインヒビターとしての置換アゾール誘導体 | |
| JPWO2008001930A1 (ja) | ピリジルイソオキサゾール誘導体 | |
| RU2006125634A (ru) | Производные амидов, несущие циклопропиламинокарбонильный заместитель, пригодные в качестве ингибиторов цитокинов |