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 (https=) | 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 (https=) |
| EP (1) | EP1635824B1 (https=) |
| JP (1) | JP2006526656A (https=) |
| AT (1) | ATE439837T1 (https=) |
| AU (1) | AU2004251668B2 (https=) |
| BR (1) | BRPI0410905A (https=) |
| CA (1) | CA2528438A1 (https=) |
| DE (1) | DE602004022668D1 (https=) |
| ES (1) | ES2332135T3 (https=) |
| MX (1) | MXPA05013075A (https=) |
| PL (1) | PL1635824T3 (https=) |
| PT (1) | PT1635824E (https=) |
| WO (1) | WO2005000298A2 (https=) |
Families Citing this family (42)
| 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 |
| EP1539291A4 (en) | 2002-09-20 | 2010-03-10 | Flowmedica Inc | METHOD AND DEVICE FOR SELECTIVE INFUSION BY CATHETER INTRA-RENAL |
| US20050197624A1 (en) | 2004-03-04 | 2005-09-08 | Flowmedica, Inc. | Sheath for use in peripheral interventions |
| EP1585572A4 (en) | 2002-09-20 | 2010-02-24 | Flowmedica Inc | METHOD AND APPARATUS FOR ADMINISTERING INTRA-AORTIC SUBSTANCE TO A BRANCHED VESSEL |
| EP1635736A2 (en) | 2003-06-05 | 2006-03-22 | FlowMedica, Inc. | Systems and methods for performing bi-lateral interventions or diagnosis in branched body lumens |
| EP1684750B1 (en) * | 2003-10-23 | 2010-04-28 | AB Science | 2-aminoaryloxazole compounds as tyrosine kinase inhibitors |
| CA2554925A1 (en) * | 2004-01-30 | 2005-08-11 | Ab Science | 2-(3-substituted-aryl)amino-4-aryl-thiazoles as tyrosine kinase inhibitors |
| CA2564751A1 (en) * | 2004-04-30 | 2005-11-24 | Schering Corporation | Neuropeptide receptor modulators |
| JP2007537298A (ja) | 2004-05-14 | 2007-12-20 | フロウメディカ， インコーポレイテッド | うっ血性心不全の処置およびｂｎｐ療法のための両側性局所腎臓送達 |
| WO2006106437A2 (en) * | 2005-04-04 | 2006-10-12 | Ab Science | Substituted oxazole derivatives and their use as tyrosine kinase inhibitors |
| UA92746C2 (en) | 2005-05-09 | 2010-12-10 | Акилайон Фармасьютикалз, Инк. | Thiazole compounds and methods of use |
| US20080207572A1 (en) * | 2005-07-14 | 2008-08-28 | 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 |
| WO2008112563A1 (en) * | 2007-03-09 | 2008-09-18 | 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 |
| US9926588B2 (en) | 2007-06-04 | 2018-03-27 | The Trustees Of The University Of Pennsylvania | 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 |
| CA2697974C (en) * | 2007-10-18 | 2015-06-30 | Janssen Pharmaceutica Nv | Trisubstituted 1,2,4-triazoles |
| US7632867B2 (en) * | 2007-10-31 | 2009-12-15 | Meta Cosmetics, Llc | Prostaglandin analog compositions to treat epithelial-related conditions |
| WO2010039535A1 (en) * | 2008-09-23 | 2010-04-08 | Meta Cosmetics, Llc | Compositions and methods to treat epithelial-related conditions |
| WO2009115547A1 (en) * | 2008-03-19 | 2009-09-24 | Janssen Pharmaceutica Nv | Trisubstituted 1, 2, 4 -triazoiies as nicotinic acetylcholine receptor modulators |
| AR071763A1 (es) * | 2008-05-09 | 2010-07-14 | Janssen Pharmaceutica Nv | Pirazoles trisustituidos, composiciones farmaceuticas que los contienen, y usos de los mismos en el tratamiento de trastornos neurologicos y psiquiatricos |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| 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 |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| 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 |
| CN108369222B (zh) * | 2015-08-31 | 2021-06-04 | 明尼苏达大学董事会 | 阿片受体调节剂及其用途 |
| 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 |
| BR112022010924A2 (pt) | 2019-12-06 | 2022-09-06 | Vertex Pharma | Tetra-hidrofuranos substituídos como moduladores de canais de sódio |
| WO2022147694A1 (en) * | 2021-01-06 | 2022-07-14 | Beijing Erai Therapeutics Co., Ltd. | Aminoheteroaryl compounds and uses thereof |
| SMT202500481T1 (it) | 2021-06-04 | 2026-01-12 | Vertex Pharma | N-(idrossialchil(etero)aril)tetraidrofuran carbossammidi come modulatori di canali del sodio |
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 |
| GB1429184A (en) * | 1972-04-20 | 1976-03-24 | Allen & Hanburys Ltd | Physically anti-inflammatory steroids for use in aerosols |
| US4044126A (en) * | 1972-04-20 | 1977-08-23 | Allen & Hanburys Limited | Steroidal aerosol compositions and process for the preparation thereof |
| 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 |
| US4328245A (en) * | 1981-02-13 | 1982-05-04 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
| US4410545A (en) * | 1981-02-13 | 1983-10-18 | 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 |
| US5033252A (en) * | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| US5052558A (en) * | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged 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 |
| PL187516B1 (pl) * | 1996-01-11 | 2004-07-30 | Smithkline Beecham Corp | Nowe podstawione pochodne imidazolu, sposób ich wytwarzania oraz kompozycja farmaceutyczna zawierająca te związki |
| DE69710319T2 (de) * | 1996-03-29 | 2002-08-14 | G.D. SEARLE & CO., CHICAGO | Para-substituierte phenylpropansäure derivate als integrin-antagonisten |
| 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 |
| IL132736A0 (en) * | 1997-05-22 | 2001-03-19 | Searle & Co | 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 |
| PL342447A1 (en) | 1997-10-27 | 2001-06-04 | Agouron Pharma | Substituted 4-amino thiazol-2-yl compounds as inhibitors of cyclin-dependent kinases |
| US6130235A (en) * | 1998-05-22 | 2000-10-10 | Scios Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| MXPA01002173A (es) | 1998-08-28 | 2003-07-14 | Scios Inc | Inhibidores de p38-alfa cinasa. |
| JP2002526482A (ja) * | 1998-09-18 | 2002-08-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | ｐ３８のインヒビター |
| WO2000025780A1 (en) | 1998-10-29 | 2000-05-11 | 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 |
| EP1169038B9 (en) | 1999-04-15 | 2013-07-10 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| GB9924092D0 (en) | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
| ES2237470T3 (es) | 1999-11-10 | 2005-08-01 | Ortho-Mcneil Pharmaceutical, Inc. | 2-aril-3-(heteroaril)-imidazo(1,2-alfa)pirimidinas sustituidas; y composiciones farmaceuticas y procedimientos asociados. |
| AU2001230026A1 (en) | 2000-02-04 | 2001-08-14 | Novo-Nordisk A/S | 2,4-diaminothiazole derivatives |
| US6586453B2 (en) * | 2000-04-03 | 2003-07-01 | 3-Dimensional Pharmaceuticals, Inc. | Substituted thiazoles and the use thereof as inhibitors of plasminogen activator inhibitor-1 |
| JP2004509863A (ja) | 2000-09-21 | 2004-04-02 | ブリストル−マイヤーズ スクイブ カンパニー | 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 |
| GEP20063915B (en) | 2000-11-17 | 2006-09-11 | Bristol Myers Squibb Co | PYRROLOTRIAZINE COMPOUNDS USEFUL AS KINASE INHIBITORS AND USE THEREOF FOR TREATING p38 KINASE-ASSOCIATED CONDITIONS |
| 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. |
| GB0124933D0 (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 |
| GB0124932D0 (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 |
| GB0124941D0 (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 |
| GB0124934D0 (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 |
| GB0124928D0 (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 |
| JP2006517234A (ja) * | 2003-02-10 | 2006-07-20 | アムジエン・インコーポレーテツド | バニロイド受容体リガンドおよび治療におけるこれらのリガンドの使用 |
| EP1684750B1 (en) * | 2003-10-23 | 2010-04-28 | AB Science | 2-aminoaryloxazole compounds as tyrosine kinase inhibitors |
-
2004
- 2004-06-02 US US10/860,768 patent/US7652044B2/en not_active Expired - Fee Related
- 2004-06-02 DE DE602004022668T patent/DE602004022668D1/de not_active Expired - Lifetime
- 2004-06-02 WO PCT/US2004/017580 patent/WO2005000298A2/en not_active Ceased
- 2004-06-02 MX MXPA05013075A patent/MXPA05013075A/es active IP Right Grant
- 2004-06-02 AT AT04754233T patent/ATE439837T1/de not_active IP Right Cessation
- 2004-06-02 BR BRPI0410905-8A patent/BRPI0410905A/pt not_active IP Right Cessation
- 2004-06-02 PT PT04754233T patent/PT1635824E/pt unknown
- 2004-06-02 CA CA002528438A patent/CA2528438A1/en not_active Abandoned
- 2004-06-02 ES ES04754233T patent/ES2332135T3/es not_active Expired - Lifetime
- 2004-06-02 AU AU2004251668A patent/AU2004251668B2/en not_active Ceased
- 2004-06-02 EP EP04754233A patent/EP1635824B1/en not_active Expired - Lifetime
- 2004-06-02 PL PL04754233T patent/PL1635824T3/pl unknown
- 2004-06-02 JP JP2006515154A patent/JP2006526656A/ja active Pending
-
2009
- 2009-09-11 US US12/557,835 patent/US20100004298A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2006526656A5 (https=) | ||
| 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 (https=) | ||
| JP2010513283A5 (https=) | ||
| 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 | |
| JP2014513122A5 (https=) | ||
| ES2220504T3 (es) | Derivados del aminotiazol y su uso como ligandos receptores de crf. | |
| CA2260263A1 (en) | Novel thiophene derivative and pharmaceutical composition thereof | |
| MXPA06005736A (es) | Compuestos de quinazolinona con bioacumulacion reducida. | |
| JPWO2008001930A1 (ja) | ピリジルイソオキサゾール誘導体 | |
| WO2002024200A1 (en) | Substituted azole derivatives as inhibitors of corticotropin releasing factor | |
| RU2006125634A (ru) | Производные амидов, несущие циклопропиламинокарбонильный заместитель, пригодные в качестве ингибиторов цитокинов |