ES2373646T3 - Compuestos de 2,4-pirimidindiamina y sus aplicaciones. - Google Patents
Compuestos de 2,4-pirimidindiamina y sus aplicaciones. Download PDFInfo
- Publication number
- ES2373646T3 ES2373646T3 ES03707654T ES03707654T ES2373646T3 ES 2373646 T3 ES2373646 T3 ES 2373646T3 ES 03707654 T ES03707654 T ES 03707654T ES 03707654 T ES03707654 T ES 03707654T ES 2373646 T3 ES2373646 T3 ES 2373646T3
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- Prior art keywords
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- fluoro
- compound
- chloro
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- Prior art date
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- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical class NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 title claims abstract description 90
- -1 tri-substituted phenyl Chemical group 0.000 claims abstract description 310
- 150000001875 compounds Chemical class 0.000 claims abstract description 309
- 150000003839 salts Chemical class 0.000 claims abstract description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 61
- 125000003118 aryl group Chemical group 0.000 claims abstract description 56
- 239000012453 solvate Substances 0.000 claims abstract description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
- 239000001257 hydrogen Substances 0.000 claims abstract description 47
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 44
- 125000006239 protecting group Chemical group 0.000 claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 26
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 25
- 150000004677 hydrates Chemical class 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 18
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 18
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 18
- 150000002148 esters Chemical class 0.000 claims abstract description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 16
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 15
- 229910052705 radium Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 12
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims abstract description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims abstract description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims abstract description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 7
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 6
- 150000005215 alkyl ethers Chemical class 0.000 claims abstract description 6
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 229910052702 rhenium Inorganic materials 0.000 claims abstract description 6
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims abstract description 6
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- RKCSEXIHMPENAW-UHFFFAOYSA-N 2-n,4-n-bis(2,4-dimethylphenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound CC1=CC(C)=CC=C1NC1=NC=C(F)C(NC=2C(=CC(C)=CC=2)C)=N1 RKCSEXIHMPENAW-UHFFFAOYSA-N 0.000 claims abstract description 5
- XCTIXWOSNPWXFO-UHFFFAOYSA-N 2-n,4-n-bis(2,5-dimethylphenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound CC1=CC=C(C)C(NC=2N=C(NC=3C(=CC=C(C)C=3)C)C(F)=CN=2)=C1 XCTIXWOSNPWXFO-UHFFFAOYSA-N 0.000 claims abstract description 5
- ATWJGWADQOMRDI-UHFFFAOYSA-N 2-n,4-n-bis(3,4-dimethylphenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound C1=C(C)C(C)=CC=C1NC1=NC=C(F)C(NC=2C=C(C)C(C)=CC=2)=N1 ATWJGWADQOMRDI-UHFFFAOYSA-N 0.000 claims abstract description 5
- JMFBVEWGVFCOKD-UHFFFAOYSA-N 2-n,4-n-bis(3-bromophenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound N1=C(NC=2C=C(Br)C=CC=2)C(F)=CN=C1NC1=CC=CC(Br)=C1 JMFBVEWGVFCOKD-UHFFFAOYSA-N 0.000 claims abstract description 5
- ARYRWGCJHFZYEP-UHFFFAOYSA-N 2-n,4-n-bis(3-chloro-4-methoxyphenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound C1=C(Cl)C(OC)=CC=C1NC1=NC=C(F)C(NC=2C=C(Cl)C(OC)=CC=2)=N1 ARYRWGCJHFZYEP-UHFFFAOYSA-N 0.000 claims abstract description 5
- RUPMYJYSOQCMBT-UHFFFAOYSA-N 2-n,4-n-bis(3-chlorophenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound N1=C(NC=2C=C(Cl)C=CC=2)C(F)=CN=C1NC1=CC=CC(Cl)=C1 RUPMYJYSOQCMBT-UHFFFAOYSA-N 0.000 claims abstract description 5
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 claims abstract description 5
- QLWNEJVSSURHRR-UHFFFAOYSA-N 5-fluoro-2-n,4-n-bis(3-methylphenyl)pyrimidine-2,4-diamine Chemical compound CC1=CC=CC(NC=2N=C(NC=3C=C(C)C=CC=3)C(F)=CN=2)=C1 QLWNEJVSSURHRR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims abstract description 5
- 229920001774 Perfluoroether Polymers 0.000 claims abstract description 5
- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 5
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 5
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 5
- 150000002475 indoles Chemical class 0.000 claims abstract description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 3
- WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 claims description 139
- 230000019491 signal transduction Effects 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 76
- 102000000551 Syk Kinase Human genes 0.000 claims description 70
- 108010016672 Syk Kinase Proteins 0.000 claims description 70
- 210000004027 cell Anatomy 0.000 claims description 63
- 238000000034 method Methods 0.000 claims description 56
- 125000001424 substituent group Chemical group 0.000 claims description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 53
- 201000010099 disease Diseases 0.000 claims description 45
- 150000001412 amines Chemical class 0.000 claims description 41
- 238000003786 synthesis reaction Methods 0.000 claims description 41
- 230000015572 biosynthetic process Effects 0.000 claims description 40
- 108010087819 Fc receptors Proteins 0.000 claims description 38
- 102000009109 Fc receptors Human genes 0.000 claims description 38
- 210000003630 histaminocyte Anatomy 0.000 claims description 37
- 210000003651 basophil Anatomy 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 238000000099 in vitro assay Methods 0.000 claims description 17
- TVKGTSHBQZEFEE-UHFFFAOYSA-N 3-[[5-fluoro-2-(3-hydroxyanilino)pyrimidin-4-yl]amino]phenol Chemical compound OC1=CC=CC(NC=2N=C(NC=3C=C(O)C=CC=3)C(F)=CN=2)=C1 TVKGTSHBQZEFEE-UHFFFAOYSA-N 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 239000000710 homodimer Substances 0.000 claims description 16
- 206010020751 Hypersensitivity Diseases 0.000 claims description 15
- 241001465754 Metazoa Species 0.000 claims description 14
- 208000026935 allergic disease Diseases 0.000 claims description 14
- 208000006673 asthma Diseases 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 239000003112 inhibitor Substances 0.000 claims description 14
- 210000003979 eosinophil Anatomy 0.000 claims description 13
- 238000000338 in vitro Methods 0.000 claims description 13
- 210000000440 neutrophil Anatomy 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 11
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- 241000282414 Homo sapiens Species 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 230000037390 scarring Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- YCHAOQCQTCZKIA-UHFFFAOYSA-N 2,2-difluoro-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)C(F)(F)OC2=C1 YCHAOQCQTCZKIA-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 6
- 206010039710 Scleroderma Diseases 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 230000001965 increasing effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- RLHKNJYBMPFYGX-UHFFFAOYSA-N 3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]phenol Chemical compound OC1=CC=CC(NC=2C(=CN=C(Cl)N=2)F)=C1 RLHKNJYBMPFYGX-UHFFFAOYSA-N 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000002260 Keloid Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 206010063837 Reperfusion injury Diseases 0.000 claims description 4
- 206010039580 Scar Diseases 0.000 claims description 4
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 230000002052 anaphylactic effect Effects 0.000 claims description 4
- 208000003455 anaphylaxis Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 230000004761 fibrosis Effects 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 210000001117 keloid Anatomy 0.000 claims description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 4
- LJRUKUQEIHJTEL-UHFFFAOYSA-N 2,2-dimethyl-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)C(C)(C)OC2=C1 LJRUKUQEIHJTEL-UHFFFAOYSA-N 0.000 claims description 3
- KSDCXJYIHUDQLT-UHFFFAOYSA-N 2-chloro-5-fluoro-n-[3-(trifluoromethoxy)phenyl]pyrimidin-4-amine Chemical compound FC1=CN=C(Cl)N=C1NC1=CC=CC(OC(F)(F)F)=C1 KSDCXJYIHUDQLT-UHFFFAOYSA-N 0.000 claims description 3
- CTIJRVCLQVLJMD-UHFFFAOYSA-N 2-chloro-n-[3-chloro-4-(trifluoromethoxy)phenyl]-5-fluoropyrimidin-4-amine Chemical compound FC1=CN=C(Cl)N=C1NC1=CC=C(OC(F)(F)F)C(Cl)=C1 CTIJRVCLQVLJMD-UHFFFAOYSA-N 0.000 claims description 3
- CFHJEIDAGOQZSR-UHFFFAOYSA-N 4-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-2,3-dimethylphenol Chemical compound CC1=C(O)C=CC(NC=2C(=CN=C(Cl)N=2)F)=C1C CFHJEIDAGOQZSR-UHFFFAOYSA-N 0.000 claims description 3
- VBCQTAKBOBAXOU-UHFFFAOYSA-N 5-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-2-methoxy-n-methylbenzamide Chemical compound C1=C(OC)C(C(=O)NC)=CC(NC=2C(=CN=C(Cl)N=2)F)=C1 VBCQTAKBOBAXOU-UHFFFAOYSA-N 0.000 claims description 3
- 208000004262 Food Hypersensitivity Diseases 0.000 claims description 3
- 235000020932 food allergy Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- ONDPXXBSJNCOSA-UHFFFAOYSA-N tert-butyl n-[[5-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-2-methoxycyclohexa-2,4-dien-1-ylidene]methyl]-n-propan-2-ylcarbamate Chemical compound C1C(=CN(C(C)C)C(=O)OC(C)(C)C)C(OC)=CC=C1NC1=NC(Cl)=NC=C1F ONDPXXBSJNCOSA-UHFFFAOYSA-N 0.000 claims description 3
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 2
- ZFUMNLUXIRJNID-UHFFFAOYSA-N 2-chloro-n-(4-chloro-3-methoxyphenyl)-5-fluoropyrimidin-4-amine Chemical compound C1=C(Cl)C(OC)=CC(NC=2C(=CN=C(Cl)N=2)F)=C1 ZFUMNLUXIRJNID-UHFFFAOYSA-N 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940124638 COX inhibitor Drugs 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 229940125715 antihistaminic agent Drugs 0.000 claims description 2
- 239000000739 antihistaminic agent Substances 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 102000003835 leukotriene receptors Human genes 0.000 claims description 2
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- 239000012528 membrane Substances 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 2
- 229960004641 rituximab Drugs 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002750 tryptase inhibitor Substances 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 206010002198 Anaphylactic reaction Diseases 0.000 claims 2
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims 2
- 206010010741 Conjunctivitis Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 230000002107 myocardial effect Effects 0.000 claims 2
- 210000004165 myocardium Anatomy 0.000 claims 2
- 206010039083 rhinitis Diseases 0.000 claims 2
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 1
- JQCXZCHTJVMZMB-UHFFFAOYSA-N 2-[3-[(4-amino-5-fluoropyrimidin-2-yl)amino]phenoxy]-N-methylacetamide Chemical compound FC=1C(=NC(=NC=1)NC1=CC(=CC=C1)OCC(=O)NC)N JQCXZCHTJVMZMB-UHFFFAOYSA-N 0.000 claims 1
- HKJOLNFQZYWWPY-UHFFFAOYSA-N 2-chloro-5-fluoro-n-(3-phenylmethoxyphenyl)pyrimidin-4-amine Chemical compound FC1=CN=C(Cl)N=C1NC1=CC=CC(OCC=2C=CC=CC=2)=C1 HKJOLNFQZYWWPY-UHFFFAOYSA-N 0.000 claims 1
- ZXSVSCZBXNJNJL-UHFFFAOYSA-N C1C(=CO)C(OC)=CC=C1NC1=NC(Cl)=NC=C1F Chemical compound C1C(=CO)C(OC)=CC=C1NC1=NC(Cl)=NC=C1F ZXSVSCZBXNJNJL-UHFFFAOYSA-N 0.000 claims 1
- 239000012826 P38 inhibitor Substances 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 claims 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 270
- 238000002360 preparation method Methods 0.000 description 183
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2009
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2010
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2013
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