RU2411245C9 - Новые производные 5,7-дизамещенного [1,3] тиазоло[4,5-d]пиримидин-2(3h)-она - Google Patents
Новые производные 5,7-дизамещенного [1,3] тиазоло[4,5-d]пиримидин-2(3h)-она Download PDFInfo
- Publication number
- RU2411245C9 RU2411245C9 RU2007140552/04A RU2007140552A RU2411245C9 RU 2411245 C9 RU2411245 C9 RU 2411245C9 RU 2007140552/04 A RU2007140552/04 A RU 2007140552/04A RU 2007140552 A RU2007140552 A RU 2007140552A RU 2411245 C9 RU2411245 C9 RU 2411245C9
- Authority
- RU
- Russia
- Prior art keywords
- amino
- thiazolo
- pyrimidin
- thio
- hydroxymethyl
- Prior art date
Links
- -1 5, 7-disubstituted [1, 3] thiazolo[4, 5-d] pyrimidine-2(3h)-one Chemical class 0.000 title claims abstract description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 239000003085 diluting agent Substances 0.000 claims abstract description 8
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 7
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 53
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- DCSLKYLPOSSKFY-UHFFFAOYSA-N 3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound C1=NC=C2SC(=O)NC2=N1 DCSLKYLPOSSKFY-UHFFFAOYSA-N 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 19
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 16
- 108010024114 Complement 3b Receptors Proteins 0.000 claims description 11
- 102000015612 Complement 3b Receptors Human genes 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
- 230000008485 antagonism Effects 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- XKANTJCXJIVELF-SWLSCSKDSA-N 3-[(1s)-1-[[7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-2-oxo-3h-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(C#N)=C1 XKANTJCXJIVELF-SWLSCSKDSA-N 0.000 claims description 4
- COQNFUICOUPODA-SMDDNHRTSA-N 3-[(1s)-1-[[7-[[(2r)-1-hydroxypentan-2-yl]amino]-2-oxo-3h-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CCC)=CC=CC(C#N)=C1 COQNFUICOUPODA-SMDDNHRTSA-N 0.000 claims description 3
- HWDVOYPLQLJXFV-TZMCWYRMSA-N 7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[(1r)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound C1([C@@H](C)SC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(S(C)(=O)=O)=C1 HWDVOYPLQLJXFV-TZMCWYRMSA-N 0.000 claims description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
- 150000003573 thiols Chemical class 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 3
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 abstract 2
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 abstract 2
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 238000007429 general method Methods 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 238000000034 method Methods 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- 239000002904 solvent Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 201000001320 Atherosclerosis Diseases 0.000 description 9
- 230000003143 atherosclerotic effect Effects 0.000 description 9
- 238000002953 preparative HPLC Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- OGRDDYIZJRCWSP-ZCFIWIBFSA-N 2-amino-7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-4h-[1,3]thiazolo[4,5-d]pyrimidine-5-thione Chemical compound CC(C)C[C@H](CO)NC1=NC(S)=NC2=C1SC(N)=N2 OGRDDYIZJRCWSP-ZCFIWIBFSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 102000019034 Chemokines Human genes 0.000 description 7
- 108010012236 Chemokines Proteins 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- BSNIDVZGHKZWDV-ZCFIWIBFSA-N 1-[(1r)-1-chloroethyl]-2-fluorobenzene Chemical compound C[C@@H](Cl)C1=CC=CC=C1F BSNIDVZGHKZWDV-ZCFIWIBFSA-N 0.000 description 5
- ROCKEAUKYWCFGR-VXGBXAGGSA-N 7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[[7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-2-oxo-3h-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound CC(C)C[C@H](CO)NC1=C2SC(=O)NC2=NC(SSC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CC(C)C)=N1 ROCKEAUKYWCFGR-VXGBXAGGSA-N 0.000 description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
- 102100030886 Complement receptor type 1 Human genes 0.000 description 5
- 208000016192 Demyelinating disease Diseases 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 5
- 102000002791 Interleukin-8B Receptors Human genes 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 238000009739 binding Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- AMQJEAYHLZJPGS-UHFFFAOYSA-N n-butyl carbinol Natural products CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 5
- RKGYXEVHTDVBLJ-RXMQYKEDSA-N 2-amino-7-[[(2r)-1-hydroxypentan-2-yl]amino]-4h-[1,3]thiazolo[4,5-d]pyrimidine-5-thione Chemical compound N1C(=S)N=C2N=C(N)SC2=C1N[C@@H](CO)CCC RKGYXEVHTDVBLJ-RXMQYKEDSA-N 0.000 description 4
- RIKQYFNEBDGPNT-SSDOTTSWSA-N 3-[(1r)-1-chloroethyl]benzonitrile Chemical compound C[C@@H](Cl)C1=CC=CC(C#N)=C1 RIKQYFNEBDGPNT-SSDOTTSWSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 4
- 102000013818 Fractalkine Human genes 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000007214 atherothrombosis Effects 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- 208000030613 peripheral artery disease Diseases 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- SXFYVXSOEBCFLV-LURJTMIESA-N (1s)-1-(2-fluorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC=C1F SXFYVXSOEBCFLV-LURJTMIESA-N 0.000 description 3
- KXBGSIFAYKVMKG-UHFFFAOYSA-N 1-(3-methylsulfonylphenyl)ethanone Chemical compound CC(=O)C1=CC=CC(S(C)(=O)=O)=C1 KXBGSIFAYKVMKG-UHFFFAOYSA-N 0.000 description 3
- XXXFPGQYDVAWMQ-SSDOTTSWSA-N 1-[(1r)-1-chloroethyl]-3-methylsulfonylbenzene Chemical compound C[C@@H](Cl)C1=CC=CC(S(C)(=O)=O)=C1 XXXFPGQYDVAWMQ-SSDOTTSWSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- ZGFGALOARUPOBS-ZETCQYMHSA-N 3-[(1s)-1-hydroxyethyl]benzonitrile Chemical compound C[C@H](O)C1=CC=CC(C#N)=C1 ZGFGALOARUPOBS-ZETCQYMHSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 0 CC(C)(*)CC(CO)N(*)c(nc(nc1N2)SC(*)C3=CC=C*(*)C=C3)c1SC2=O Chemical compound CC(C)(*)CC(CO)N(*)c(nc(nc1N2)SC(*)C3=CC=C*(*)C=C3)c1SC2=O 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- GTLWADFFABIGAE-SSDOTTSWSA-N [(1r)-1-chloroethyl]benzene Chemical compound C[C@@H](Cl)C1=CC=CC=C1 GTLWADFFABIGAE-SSDOTTSWSA-N 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 3
- 229940096397 interleukin-8 Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- AIQAQFDMERPUAH-SSDOTTSWSA-N (1r)-1-(3-methylsulfonylphenyl)ethanol Chemical compound C[C@@H](O)C1=CC=CC(S(C)(=O)=O)=C1 AIQAQFDMERPUAH-SSDOTTSWSA-N 0.000 description 2
- YESOPGLEIJQAEF-LURJTMIESA-N (1s)-1-(3-fluorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC(F)=C1 YESOPGLEIJQAEF-LURJTMIESA-N 0.000 description 2
- AIQAQFDMERPUAH-ZETCQYMHSA-N (1s)-1-(3-methylsulfonylphenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC(S(C)(=O)=O)=C1 AIQAQFDMERPUAH-ZETCQYMHSA-N 0.000 description 2
- ZJTOCCMPRIUOGK-TZMCWYRMSA-N (2r)-2-[[2-amino-5-[(1r)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(S(C)(=O)=O)=C1 ZJTOCCMPRIUOGK-TZMCWYRMSA-N 0.000 description 2
- LBAMGFHXEZOCSA-WDEREUQCSA-N (2r)-2-[[2-amino-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-fluoro-4-methylpentan-1-ol Chemical compound C1([C@@H](SC=2N=C3N=C(N)SC3=C(N[C@@H](CO)CC(C)(C)F)N=2)C)=CC=CC=C1F LBAMGFHXEZOCSA-WDEREUQCSA-N 0.000 description 2
- ZJTOCCMPRIUOGK-GXTWGEPZSA-N (2r)-2-[[2-amino-5-[(1s)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(S(C)(=O)=O)=C1 ZJTOCCMPRIUOGK-GXTWGEPZSA-N 0.000 description 2
- XHVPKBSWHXNIAV-VXGBXAGGSA-N (2r)-2-[[2-chloro-5-[[2-chloro-7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](CO)NC1=C2SC(Cl)=NC2=NC(SSC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=N1 XHVPKBSWHXNIAV-VXGBXAGGSA-N 0.000 description 2
- ZPLAZJAXKZXHCR-DZGCQCFKSA-N (2r)-2-[[2-methoxy-5-[(1s)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=CC=CC(S(C)(=O)=O)=C1 ZPLAZJAXKZXHCR-DZGCQCFKSA-N 0.000 description 2
- APRPJELLNWTHJA-QWHCGFSZSA-N (2r)-2-[[5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=CC=CC=C1F APRPJELLNWTHJA-QWHCGFSZSA-N 0.000 description 2
- UIXYMPYXXUVSBH-NWDGAFQWSA-N (2r)-2-[[5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(OC)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC=C1F UIXYMPYXXUVSBH-NWDGAFQWSA-N 0.000 description 2
- VHXRWIWCIZQGOO-SWLSCSKDSA-N (2r)-2-[[5-[(1s)-1-(3-fluorophenyl)ethyl]sulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=CC=CC(F)=C1 VHXRWIWCIZQGOO-SWLSCSKDSA-N 0.000 description 2
- ZQEJUHXTNTWAPC-ZIAGYGMSSA-N (2r)-2-[[5-[[7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](CO)NC1=C2SC(OC)=NC2=NC(SSC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=N1 ZQEJUHXTNTWAPC-ZIAGYGMSSA-N 0.000 description 2
- JVFYARMZHJAWRK-VXGBXAGGSA-N (2r)-2-[[5-[[7-[[(2r)-1-hydroxypentan-2-yl]amino]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pentan-1-ol Chemical compound CCC[C@H](CO)NC1=C2SC(OC)=NC2=NC(SSC=2N=C(C=3SC(OC)=NC=3N=2)N[C@@H](CO)CCC)=N1 JVFYARMZHJAWRK-VXGBXAGGSA-N 0.000 description 2
- NLHAOTKLNPSOAZ-NWDGAFQWSA-N (2r)-4-fluoro-2-[[5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)(C)F)N=2)OC)=CC=CC=C1F NLHAOTKLNPSOAZ-NWDGAFQWSA-N 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- XXXFPGQYDVAWMQ-UHFFFAOYSA-N 1-(1-chloroethyl)-3-methylsulfonylbenzene Chemical compound CC(Cl)C1=CC=CC(S(C)(=O)=O)=C1 XXXFPGQYDVAWMQ-UHFFFAOYSA-N 0.000 description 2
- AIQAQFDMERPUAH-UHFFFAOYSA-N 1-(3-methylsulfonylphenyl)ethanol Chemical compound CC(O)C1=CC=CC(S(C)(=O)=O)=C1 AIQAQFDMERPUAH-UHFFFAOYSA-N 0.000 description 2
- JRVORWRZZBKIBX-ZCFIWIBFSA-N 1-[(1r)-1-chloroethyl]-3-fluorobenzene Chemical compound C[C@@H](Cl)C1=CC=CC(F)=C1 JRVORWRZZBKIBX-ZCFIWIBFSA-N 0.000 description 2
- PXGSOIQQPQSTRO-SWLSCSKDSA-N 3-[(1s)-1-[[2-amino-7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(C#N)=C1 PXGSOIQQPQSTRO-SWLSCSKDSA-N 0.000 description 2
- PNKYTKPWPKRAKI-SMDDNHRTSA-N 3-[(1s)-1-[[2-amino-7-[[(2r)-1-hydroxypentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC(C#N)=C1 PNKYTKPWPKRAKI-SMDDNHRTSA-N 0.000 description 2
- LULCGGSOYKHPTH-SWLSCSKDSA-N 3-[(1s)-1-[[2-chloro-7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(C#N)=C1 LULCGGSOYKHPTH-SWLSCSKDSA-N 0.000 description 2
- QQQMSIMRGAPTJT-XJKSGUPXSA-N 3-[(1s)-1-[[7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=CC=CC(C#N)=C1 QQQMSIMRGAPTJT-XJKSGUPXSA-N 0.000 description 2
- BNPZENCUZCVMBA-SWLSCSKDSA-N 3-[(1s)-1-[[7-[[(2r)-1-hydroxypentan-2-yl]amino]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(OC)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC(C#N)=C1 BNPZENCUZCVMBA-SWLSCSKDSA-N 0.000 description 2
- OVSMURBVBQUOSF-UHFFFAOYSA-N 3-methylsulfonylbenzaldehyde Chemical compound CS(=O)(=O)C1=CC=CC(C=O)=C1 OVSMURBVBQUOSF-UHFFFAOYSA-N 0.000 description 2
- 102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 description 2
- 108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 description 2
- SJNSPSXSWUZBQZ-UHFFFAOYSA-N 5-benzylsulfanyl-7-chloro-[1,3]thiazolo[4,5-d]pyrimidin-2-amine Chemical compound N=1C(Cl)=C2SC(N)=NC2=NC=1SCC1=CC=CC=C1 SJNSPSXSWUZBQZ-UHFFFAOYSA-N 0.000 description 2
- IAGWEZFSRRPOSS-GXTWGEPZSA-N 7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[(1s)-1-phenylethyl]sulfanyl-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound C1([C@H](C)SC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1 IAGWEZFSRRPOSS-GXTWGEPZSA-N 0.000 description 2
- HWDVOYPLQLJXFV-TYZXPVIJSA-N 7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[1-(3-methylsulfonylphenyl)ethylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SC(C)C1=CC=CC(S(C)(=O)=O)=C1 HWDVOYPLQLJXFV-TYZXPVIJSA-N 0.000 description 2
- QEGZCVZSDLFVEI-WCQYABFASA-N 7-[[(2r)-1-hydroxypentan-2-yl]amino]-5-[(1s)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound C1([C@H](C)SC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CCC)=CC=CC(S(C)(=O)=O)=C1 QEGZCVZSDLFVEI-WCQYABFASA-N 0.000 description 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 2
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 2
- 108010001478 Bacitracin Proteins 0.000 description 2
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 2
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 2
- 229940077672 Ileal bile acid transport inhibitor Drugs 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102100036154 Platelet basic protein Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108010084455 Zeocin Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 229960003071 bacitracin Drugs 0.000 description 2
- 229930184125 bacitracin Natural products 0.000 description 2
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000000451 chemical ionisation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 108010035886 connective tissue-activating peptide Proteins 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- UFPQIRYSPUYQHK-WAQVJNLQSA-N leukotriene A4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O UFPQIRYSPUYQHK-WAQVJNLQSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 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
- AILYJCHMDSZEOL-VGMFFHCQSA-N (1S)-1-phenylethanol Chemical compound C1(=CC=CC=C1)[C@H](C)O.C1(=CC=CC=C1)[C@H](C)O AILYJCHMDSZEOL-VGMFFHCQSA-N 0.000 description 1
- ZPLAZJAXKZXHCR-UKRRQHHQSA-N (2R)-2-[[2-methoxy-5-[(1R)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound COC=1SC2=C(N=C(N=C2N[C@@H](CO)CC(C)C)S[C@H](C)C2=CC(=CC=C2)S(=O)(=O)C)N1 ZPLAZJAXKZXHCR-UKRRQHHQSA-N 0.000 description 1
- LYZBESBXJHUNLT-GFCCVEGCSA-N (2r)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]pentan-1-ol Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CO)CCC)=NC=1SCC1=CC=CC=C1 LYZBESBXJHUNLT-GFCCVEGCSA-N 0.000 description 1
- AHBUPDWDDPROSS-CYBMUJFWSA-N (2r)-2-[(5-benzylsulfanyl-2-bromo-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SCC1=CC=CC=C1 AHBUPDWDDPROSS-CYBMUJFWSA-N 0.000 description 1
- ZMQSLMZOWVGBSM-TYZXPVIJSA-N (2r)-2-[[2-amino-5-(1-phenylethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SC(C)C1=CC=CC=C1 ZMQSLMZOWVGBSM-TYZXPVIJSA-N 0.000 description 1
- ZMQSLMZOWVGBSM-TZMCWYRMSA-N (2r)-2-[[2-amino-5-[(1r)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1 ZMQSLMZOWVGBSM-TZMCWYRMSA-N 0.000 description 1
- PQYZCJMYDYNLKP-NWDGAFQWSA-N (2r)-2-[[2-amino-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1F PQYZCJMYDYNLKP-NWDGAFQWSA-N 0.000 description 1
- HNGCDCABVYTVAE-WDEREUQCSA-N (2r)-2-[[2-amino-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC=C1F HNGCDCABVYTVAE-WDEREUQCSA-N 0.000 description 1
- GDKZGPOPQDQWKT-SMDDNHRTSA-N (2r)-2-[[2-amino-5-[(1s)-1-(3-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(F)=C1 GDKZGPOPQDQWKT-SMDDNHRTSA-N 0.000 description 1
- ZMQSLMZOWVGBSM-GXTWGEPZSA-N (2r)-2-[[2-amino-5-[(1s)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(N)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1 ZMQSLMZOWVGBSM-GXTWGEPZSA-N 0.000 description 1
- LNYPCOTUSORTGE-TYZXPVIJSA-N (2r)-2-[[2-chloro-5-(1-phenylethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound N=1C=2N=C(Cl)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SC(C)C1=CC=CC=C1 LNYPCOTUSORTGE-TYZXPVIJSA-N 0.000 description 1
- XTXRULPCPUTNPK-TZMCWYRMSA-N (2r)-2-[[2-chloro-5-[(1r)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(S(C)(=O)=O)=C1 XTXRULPCPUTNPK-TZMCWYRMSA-N 0.000 description 1
- FVWFKJOEHYZTJC-WDEREUQCSA-N (2r)-2-[[2-chloro-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-fluoro-4-methylpentan-1-ol Chemical compound C1([C@@H](SC=2N=C3N=C(Cl)SC3=C(N[C@@H](CO)CC(C)(C)F)N=2)C)=CC=CC=C1F FVWFKJOEHYZTJC-WDEREUQCSA-N 0.000 description 1
- UOUSQKNUSALYLY-NWDGAFQWSA-N (2r)-2-[[2-chloro-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1F UOUSQKNUSALYLY-NWDGAFQWSA-N 0.000 description 1
- KRNXJIUSLJRBFQ-WDEREUQCSA-N (2r)-2-[[2-chloro-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC=C1F KRNXJIUSLJRBFQ-WDEREUQCSA-N 0.000 description 1
- AKBOVKSWNPAQAQ-SMDDNHRTSA-N (2r)-2-[[2-chloro-5-[(1s)-1-(3-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(F)=C1 AKBOVKSWNPAQAQ-SMDDNHRTSA-N 0.000 description 1
- XTXRULPCPUTNPK-GXTWGEPZSA-N (2r)-2-[[2-chloro-5-[(1s)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC(S(C)(=O)=O)=C1 XTXRULPCPUTNPK-GXTWGEPZSA-N 0.000 description 1
- LNYPCOTUSORTGE-GXTWGEPZSA-N (2r)-2-[[2-chloro-5-[(1s)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CC(C)C)=CC=CC=C1 LNYPCOTUSORTGE-GXTWGEPZSA-N 0.000 description 1
- MGUHSSFCPTWUHP-NXEZZACHSA-N (2r)-2-[[2-chloro-5-[[2-chloro-7-[[(2r)-1-hydroxypentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pentan-1-ol Chemical compound CCC[C@H](CO)NC1=C2SC(Cl)=NC2=NC(SSC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CCC)=N1 MGUHSSFCPTWUHP-NXEZZACHSA-N 0.000 description 1
- IYABMPZWIARKBQ-AWKYBWMHSA-N (2r)-2-[[2-methoxy-5-(1-phenylethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound N=1C(N[C@@H](CO)CC(C)C)=C2SC(OC)=NC2=NC=1SC(C)C1=CC=CC=C1 IYABMPZWIARKBQ-AWKYBWMHSA-N 0.000 description 1
- IYABMPZWIARKBQ-DZGCQCFKSA-N (2r)-2-[[2-methoxy-5-[(1s)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol Chemical compound C1([C@H](C)SC=2N=C3N=C(SC3=C(N[C@@H](CO)CC(C)C)N=2)OC)=CC=CC=C1 IYABMPZWIARKBQ-DZGCQCFKSA-N 0.000 description 1
- IDGOXQYHOFKAMG-RXMQYKEDSA-N (2r)-2-amino-4-fluoro-4-methylpentan-1-ol Chemical compound CC(C)(F)C[C@@H](N)CO IDGOXQYHOFKAMG-RXMQYKEDSA-N 0.000 description 1
- ULAXUFGARZZKTK-RXMQYKEDSA-N (2r)-2-aminopentan-1-ol Chemical compound CCC[C@@H](N)CO ULAXUFGARZZKTK-RXMQYKEDSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- QUPFKBITVLIQNA-KPKJPENVSA-N (5e)-2-sulfanylidene-5-[[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(\C=C\3C(NC(=S)S/3)=O)=CC=2)=C1 QUPFKBITVLIQNA-KPKJPENVSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- OGCGXUGBDJGFFY-MRXNPFEDSA-N (r)-alpha,alpha-diphenyl-2-pyrrolidinemethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)[C@H]1CCCN1 OGCGXUGBDJGFFY-MRXNPFEDSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- NRHZXDVOUGKSPA-UHFFFAOYSA-N 1-(1-bromoethyl)-2-(trifluoromethyl)benzene Chemical compound CC(Br)C1=CC=CC=C1C(F)(F)F NRHZXDVOUGKSPA-UHFFFAOYSA-N 0.000 description 1
- AJBWDFPJLDDEPQ-UHFFFAOYSA-N 1-(1-bromoethyl)-3-(trifluoromethyl)benzene Chemical compound CC(Br)C1=CC=CC(C(F)(F)F)=C1 AJBWDFPJLDDEPQ-UHFFFAOYSA-N 0.000 description 1
- CRRUGYDDEMGVDY-UHFFFAOYSA-N 1-bromoethylbenzene Chemical compound CC(Br)C1=CC=CC=C1 CRRUGYDDEMGVDY-UHFFFAOYSA-N 0.000 description 1
- MZMVVHAHSRJOEO-UHFFFAOYSA-N 1-chloropropylbenzene Chemical compound CCC(Cl)C1=CC=CC=C1 MZMVVHAHSRJOEO-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- NZQDWKCNBOELAI-KSFYIVLOSA-N 2-[(3s,4r)-3-benzyl-4-hydroxy-3,4-dihydro-2h-chromen-7-yl]-4-(trifluoromethyl)benzoic acid Chemical compound C([C@@H]1[C@H](C2=CC=C(C=C2OC1)C=1C(=CC=C(C=1)C(F)(F)F)C(O)=O)O)C1=CC=CC=C1 NZQDWKCNBOELAI-KSFYIVLOSA-N 0.000 description 1
- MYXGDITVGPGTHQ-LURJTMIESA-N 2-amino-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-4h-[1,3]thiazolo[4,5-d]pyrimidin-7-one Chemical compound C1([C@@H](SC=2N=C3N=C(N)SC3=C(O)N=2)C)=CC=CC=C1F MYXGDITVGPGTHQ-LURJTMIESA-N 0.000 description 1
- RFMRDMXTZPGZRP-UHFFFAOYSA-N 3-(1-chloroethyl)benzamide Chemical compound CC(Cl)C1=CC=CC(C(N)=O)=C1 RFMRDMXTZPGZRP-UHFFFAOYSA-N 0.000 description 1
- FNBVZXZMVMBERL-UHFFFAOYSA-N 3-(1-hydroxyethyl)benzamide Chemical compound CC(O)C1=CC=CC(C(N)=O)=C1 FNBVZXZMVMBERL-UHFFFAOYSA-N 0.000 description 1
- USJFZTZJOYYUPP-SMDDNHRTSA-N 3-[(1s)-1-[[2-chloro-7-[[(2r)-1-hydroxypentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile Chemical compound C1([C@H](C)SC=2N=C(C=3SC(Cl)=NC=3N=2)N[C@@H](CO)CCC)=CC=CC(C#N)=C1 USJFZTZJOYYUPP-SMDDNHRTSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MQLADKMVHOOVET-HXPMCKFVSA-N 5-[4-[(2s,4r)-4-hydroxy-2-methyloxan-4-yl]thiophen-2-yl]sulfanyl-1-methyl-3h-indol-2-one Chemical compound C1CO[C@@H](C)C[C@@]1(O)C1=CSC(SC=2C=C3CC(=O)N(C)C3=CC=2)=C1 MQLADKMVHOOVET-HXPMCKFVSA-N 0.000 description 1
- LOSWDIGGZMWFHV-CYBMUJFWSA-N 5-benzylsulfanyl-7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SCC1=CC=CC=C1 LOSWDIGGZMWFHV-CYBMUJFWSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- IMDZNDDKTLENQP-ZETCQYMHSA-N 6-amino-2-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-1h-pyrimidin-4-one Chemical compound S([C@@H](C)C=1C(=CC=CC=1)F)C1=NC(N)=CC(O)=N1 IMDZNDDKTLENQP-ZETCQYMHSA-N 0.000 description 1
- BWYGMIYEADAIGW-UHFFFAOYSA-N 6-amino-2-sulfanylidene-1h-pyrimidin-4-one;hydrate Chemical compound O.NC1=CC(=O)NC(=S)N1 BWYGMIYEADAIGW-UHFFFAOYSA-N 0.000 description 1
- RZURGDRYOMQZSH-SBXXRYSUSA-N 7-[[(2r)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[1-[3-(trifluoromethyl)phenyl]ethylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)CC(C)C)=NC=1SC(C)C1=CC=CC(C(F)(F)F)=C1 RZURGDRYOMQZSH-SBXXRYSUSA-N 0.000 description 1
- VWARFGODLVURDR-NXEZZACHSA-N 7-[[(2r)-1-hydroxypentan-2-yl]amino]-5-[[7-[[(2r)-1-hydroxypentan-2-yl]amino]-2-oxo-3h-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]disulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound CCC[C@H](CO)NC1=C2SC(=O)NC2=NC(SSC=2N=C(C=3SC(=O)NC=3N=2)N[C@@H](CO)CCC)=N1 VWARFGODLVURDR-NXEZZACHSA-N 0.000 description 1
- WDFMDMANXPNMRM-LURJTMIESA-N 7-chloro-5-[(1s)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-2-amine Chemical compound C1([C@@H](SC=2N=C3N=C(N)SC3=C(Cl)N=2)C)=CC=CC=C1F WDFMDMANXPNMRM-LURJTMIESA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 102000001326 Chemokine CCL4 Human genes 0.000 description 1
- 108010055165 Chemokine CCL4 Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 206010057645 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 101150061021 Cxcr2 gene Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 239000007756 Ham's F12 Nutrient Mixture Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 0.000 description 1
- 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000916059 Homo sapiens C-X-C chemokine receptor type 2 Proteins 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000746022 Homo sapiens CX3C chemokine receptor 1 Proteins 0.000 description 1
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
- 101100455054 Homo sapiens LTA4H gene Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- YFIZRWPXUYFCSN-UHFFFAOYSA-N LY293111 Chemical compound C1=CC=C(OC=2C(=CC=CC=2)C(O)=O)C(CCC)=C1OCCCOC(C(=C1)CC)=CC(O)=C1C1=CC=C(F)C=C1 YFIZRWPXUYFCSN-UHFFFAOYSA-N 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 1
- UFPQIRYSPUYQHK-VRKJBCFNSA-N Leukotriene A4 Natural products CCCCCC=C/CC=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(=O)O UFPQIRYSPUYQHK-VRKJBCFNSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 229940122159 Myeloperoxidase inhibitor Drugs 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 108091007187 Reductases Proteins 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 101100075025 Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545) LTA4 gene Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 206010072148 Stiff-Person syndrome Diseases 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 206010044696 Tropical spastic paresis Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- YWBULOYFCXZCGF-UHFFFAOYSA-N [1,3]thiazolo[4,5-d]pyrimidine Chemical class C1=NC=C2SC=NC2=N1 YWBULOYFCXZCGF-UHFFFAOYSA-N 0.000 description 1
- 229940020697 accolate Drugs 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229950001163 amelubant Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 208000025434 cerebellar degeneration Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- PSEHHVRCDVOTID-UHFFFAOYSA-N chloro-bis(4,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl)borane Chemical compound CC1C(C2(C)C)CC2CC1B(Cl)C(C1C)CC2C(C)(C)C1C2 PSEHHVRCDVOTID-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- XFLQIRAKKLNXRQ-UUWRZZSWSA-N elobixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)NCC(O)=O)C=3C=CC=CC=3)C=C2S(=O)(=O)CC(CCCC)(CCCC)CN1C1=CC=CC=C1 XFLQIRAKKLNXRQ-UUWRZZSWSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- SBVYURPQULDJTI-UHFFFAOYSA-N ethyl n-[amino-[4-[[3-[[4-[2-(4-hydroxyphenyl)propan-2-yl]phenoxy]methyl]phenyl]methoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(C(=N)NC(=O)OCC)=CC=C1OCC1=CC=CC(COC=2C=CC(=CC=2)C(C)(C)C=2C=CC(O)=CC=2)=C1 SBVYURPQULDJTI-UHFFFAOYSA-N 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 102000051339 human CX3CR1 Human genes 0.000 description 1
- 102000052624 human CXCL8 Human genes 0.000 description 1
- 102000055357 human CXCR2 Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 102000003835 leukotriene receptors Human genes 0.000 description 1
- 108090000146 leukotriene receptors Proteins 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 206010065579 multifocal motor neuropathy Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 208000020469 nerve plexus disease Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 208000012111 paraneoplastic syndrome Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000003428 phospholipase inhibitor Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 201000006380 plexopathy Diseases 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- GUUBJKMBDULZTE-UHFFFAOYSA-M potassium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[K+].OCCN1CCN(CCS(O)(=O)=O)CC1 GUUBJKMBDULZTE-UHFFFAOYSA-M 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- XNAYQOBPAXEYLI-AAGWESIMSA-M sodium;3-[[3-[(e)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoate Chemical compound [Na+].CN(C)C(=O)CCSC(SCCC([O-])=O)C1=CC=CC(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)=C1 XNAYQOBPAXEYLI-AAGWESIMSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 150000008634 thiazolopyrimidines Chemical group 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 208000006961 tropical spastic paraparesis Diseases 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
- 229960001522 ximelagatran Drugs 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0500768-7 | 2005-04-06 | ||
| SE0500768 | 2005-04-06 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2007140552A RU2007140552A (ru) | 2009-05-20 |
| RU2411245C2 RU2411245C2 (ru) | 2011-02-10 |
| RU2411245C9 true RU2411245C9 (ru) | 2011-05-27 |
Family
ID=37073738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007140552/04A RU2411245C9 (ru) | 2005-04-06 | 2006-04-03 | Новые производные 5,7-дизамещенного [1,3] тиазоло[4,5-d]пиримидин-2(3h)-она |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8088780B2 (OSRAM) |
| EP (1) | EP1869055A1 (OSRAM) |
| JP (1) | JP2008535834A (OSRAM) |
| KR (1) | KR20080004484A (OSRAM) |
| CN (1) | CN101193898B (OSRAM) |
| AR (1) | AR053347A1 (OSRAM) |
| AU (1) | AU2006231835B8 (OSRAM) |
| BR (1) | BRPI0609736A2 (OSRAM) |
| CA (1) | CA2604016A1 (OSRAM) |
| IL (1) | IL185913A0 (OSRAM) |
| MX (1) | MX2007012067A (OSRAM) |
| NO (1) | NO20075610L (OSRAM) |
| NZ (1) | NZ561462A (OSRAM) |
| RU (1) | RU2411245C9 (OSRAM) |
| TW (1) | TW200720279A (OSRAM) |
| UY (1) | UY29451A1 (OSRAM) |
| WO (1) | WO2006107257A1 (OSRAM) |
| ZA (1) | ZA200708182B (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2641815T3 (es) | 2004-10-29 | 2017-11-14 | Eisai R&D Management Co., Ltd. | Tratamiento para enfermedades inflamatorias |
| UA90707C2 (en) * | 2005-04-06 | 2010-05-25 | Астразенека Аб | Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives |
| TW200820973A (en) | 2006-09-29 | 2008-05-16 | Astrazeneca Ab | Novel compounds 480 |
| CA2714436C (en) | 2008-03-07 | 2017-06-27 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Novel 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 and p40 |
| LT2254869T (lt) | 2008-03-07 | 2017-08-10 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Nauji 1-benzil-3-hidroksimetilindazolo dariniai ir jų panaudojimas gydyme ligų, susijusių su cx3cr1 ir p40 raiška |
| JP5509102B2 (ja) | 2008-03-07 | 2014-06-04 | アジェンデ・キミケ・リウニテ・アンジェリニ・フランチェスコ・ア・チ・エレ・ア・エフェ・ソシエタ・ペル・アチオニ | 新規な１−ベンジル−３−ヒドロキシメチルインダゾール誘導体およびそのｍｃｐ−１およびｃｘ３ｃｒ１の発現に基づく疾患の治療への使用 |
| AR071036A1 (es) * | 2008-03-26 | 2010-05-19 | Astrazeneca Ab | Derivados 5, 7-disustituidos de [1, 3]tiazolo[4, 5-d]pirimidin-2 (3h)-ona, una composicion farmaceutica que los comprende y su uso en el tratamiento de enfermedades mediadas por el receptor cx3cr1. |
| EP2432776B1 (en) | 2009-05-21 | 2019-09-11 | Universite Laval | Methyl sulfanyl pyrimidines useful as antiinflammatories, analgesics, and antiepileptics |
| JO3437B1 (ar) | 2009-10-30 | 2019-10-20 | Esai R & D Man Co Ltd | أجسام مضادة محسنة مضادة للفراكتالكين البشري واستخداماتها |
| US8476301B2 (en) | 2011-09-13 | 2013-07-02 | Eisai R&D Management Co., Ltd. | Pyrrolidin-3-ylacetic acid derivative |
| JO3082B1 (ar) * | 2011-09-13 | 2017-03-15 | Eisai R&D Man Co Ltd | مشتق بيروليدين-3- يل حمض خليك |
| AU2014231863B2 (en) * | 2013-03-12 | 2017-07-27 | Eisai R&D Management Co., Ltd. | Salt of pyrrolidin-3-yl acetic acid derivative and crystals thereof |
| WO2014142086A1 (ja) * | 2013-03-13 | 2014-09-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピロリジン－３－イル酢酸誘導体およびピペリジン－３－イル酢酸誘導体 |
| EP3294745B1 (en) * | 2015-05-08 | 2020-01-01 | H. Hoffnabb-La Roche Ag | Novel oxathiolane carboxylic acids and derivatives for the treatment and prophylaxis of virus infection |
| GB201811169D0 (en) | 2018-07-06 | 2018-08-29 | Kancera Ab | New compounds |
| KR20250086780A (ko) | 2022-10-19 | 2025-06-13 | 아스트라제네카 아베 | Cx3cr1 조절제로서의 2,4,6-삼중치환된 1,3,5-트리아진 |
| WO2025219939A1 (en) | 2024-04-17 | 2025-10-23 | Astrazeneca Ab | Salts and polymorphs of cx3cr1 modulators |
| WO2025219947A1 (en) | 2024-04-18 | 2025-10-23 | Astrazeneca Ab | Thio-substituted 1,3,5-triazine cx3cr1 modulators |
| WO2025219950A1 (en) | 2024-04-18 | 2025-10-23 | Astrazeneca Ab | Small molecule cx3cr1 modulators |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001025242A1 (en) * | 1999-10-01 | 2001-04-12 | Astrazeneca Uk Limited | Novel thiazolo(4,5-d)pyrimidine compounds |
| WO2001058906A1 (en) * | 2000-02-11 | 2001-08-16 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
| RU2197493C2 (ru) * | 1997-07-18 | 2003-01-27 | Ф.Хоффманн-Ля Рош Аг | Производные 5h-тиазол[3,2-а]пиримидина, промежуточные продукты и лекарственное средство |
| WO2004026880A1 (en) * | 2002-09-20 | 2004-04-01 | Astrazeneca Ab | Novel compound |
| WO2004026835A1 (en) * | 2002-09-20 | 2004-04-01 | Astrazeneca Ab | Novel compound |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE543978A (OSRAM) | 1955-01-03 | |||
| US4698327A (en) | 1985-04-25 | 1987-10-06 | Eli Lilly And Company | Novel glycopeptide derivatives |
| US4639433A (en) | 1985-08-14 | 1987-01-27 | Eli Lilly And Company | Glycopeptide derivatives |
| US4643987A (en) | 1985-08-14 | 1987-02-17 | Eli Lilly And Company | Modified glycopeptides |
| CA2031803C (en) | 1989-12-13 | 2001-05-29 | Ramakrishnan Nagarajan | Improvements in or relating to glycopeptide deriveratives |
| US5202328A (en) | 1991-03-06 | 1993-04-13 | Merck & Co., Inc. | Substituted fused pyrimidinones |
| US5840684A (en) | 1994-01-28 | 1998-11-24 | Eli Lilly And Company | Glycopeptide antibiotic derivatives |
| WO1999051608A1 (en) | 1998-04-03 | 1999-10-14 | Du Pont Pharmaceuticals Company | THIAZOLO[4,5-d]PYRIMIDINES AND PYRIDINES AS CORTICOTROPIN RELEASING FACTOR (CRF) ANTAGONISTS |
| US6670446B1 (en) | 1998-05-01 | 2003-12-30 | Eli Lilly And Company | N1 modified glycopeptides |
| SE9802729D0 (sv) | 1998-08-13 | 1998-08-13 | Astra Pharma Prod | Novel Compounds |
| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| SE0004110L (sv) | 2000-11-10 | 2002-05-11 | Forsheda Ab | Tätningsring |
| SE0101082D0 (sv) | 2001-03-27 | 2001-03-27 | Astrazeneca Ab | Novel use |
| SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| JP2007507494A (ja) * | 2003-10-07 | 2007-03-29 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体アンタゴニストとりわけＣＸ３ＣＲ１として有用な新規な２−置換４−アミノ−チアゾロ［４，５−ｄ］ピリミジン |
| UA90707C2 (en) | 2005-04-06 | 2010-05-25 | Астразенека Аб | Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives |
-
2006
- 2006-03-27 AR ARP060101170A patent/AR053347A1/es not_active Application Discontinuation
- 2006-03-28 TW TW095110787A patent/TW200720279A/zh unknown
- 2006-04-03 KR KR1020077022814A patent/KR20080004484A/ko not_active Withdrawn
- 2006-04-03 US US11/910,781 patent/US8088780B2/en not_active Expired - Fee Related
- 2006-04-03 AU AU2006231835A patent/AU2006231835B8/en not_active Ceased
- 2006-04-03 EP EP06717077A patent/EP1869055A1/en not_active Withdrawn
- 2006-04-03 CA CA002604016A patent/CA2604016A1/en not_active Abandoned
- 2006-04-03 CN CN2006800200730A patent/CN101193898B/zh not_active Expired - Fee Related
- 2006-04-03 NZ NZ561462A patent/NZ561462A/en not_active IP Right Cessation
- 2006-04-03 MX MX2007012067A patent/MX2007012067A/es not_active Application Discontinuation
- 2006-04-03 RU RU2007140552/04A patent/RU2411245C9/ru not_active IP Right Cessation
- 2006-04-03 BR BRPI0609736-7A patent/BRPI0609736A2/pt not_active Application Discontinuation
- 2006-04-03 WO PCT/SE2006/000398 patent/WO2006107257A1/en not_active Ceased
- 2006-04-03 JP JP2008505261A patent/JP2008535834A/ja active Pending
- 2006-04-04 UY UY29451A patent/UY29451A1/es unknown
-
2007
- 2007-09-11 IL IL185913A patent/IL185913A0/en unknown
- 2007-09-25 ZA ZA200708182A patent/ZA200708182B/xx unknown
- 2007-11-05 NO NO20075610A patent/NO20075610L/no not_active Application Discontinuation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2197493C2 (ru) * | 1997-07-18 | 2003-01-27 | Ф.Хоффманн-Ля Рош Аг | Производные 5h-тиазол[3,2-а]пиримидина, промежуточные продукты и лекарственное средство |
| WO2001025242A1 (en) * | 1999-10-01 | 2001-04-12 | Astrazeneca Uk Limited | Novel thiazolo(4,5-d)pyrimidine compounds |
| WO2001058906A1 (en) * | 2000-02-11 | 2001-08-16 | Astrazeneca Ab | Pyrimidine compounds and their use as modulators of chemokine receptor activity |
| WO2004026880A1 (en) * | 2002-09-20 | 2004-04-01 | Astrazeneca Ab | Novel compound |
| WO2004026835A1 (en) * | 2002-09-20 | 2004-04-01 | Astrazeneca Ab | Novel compound |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ561462A (en) | 2010-12-24 |
| US20090124637A1 (en) | 2009-05-14 |
| EP1869055A1 (en) | 2007-12-26 |
| AU2006231835B8 (en) | 2010-10-14 |
| AR053347A1 (es) | 2007-05-02 |
| AU2006231835A1 (en) | 2006-10-12 |
| UY29451A1 (es) | 2006-11-30 |
| BRPI0609736A2 (pt) | 2011-10-18 |
| KR20080004484A (ko) | 2008-01-09 |
| RU2007140552A (ru) | 2009-05-20 |
| IL185913A0 (en) | 2008-01-06 |
| JP2008535834A (ja) | 2008-09-04 |
| AU2006231835B2 (en) | 2010-09-30 |
| NO20075610L (no) | 2008-01-07 |
| US8088780B2 (en) | 2012-01-03 |
| CN101193898B (zh) | 2010-12-01 |
| TW200720279A (en) | 2007-06-01 |
| CN101193898A (zh) | 2008-06-04 |
| ZA200708182B (en) | 2008-11-26 |
| MX2007012067A (es) | 2007-12-04 |
| CA2604016A1 (en) | 2006-10-12 |
| WO2006107257A1 (en) | 2006-10-12 |
| RU2411245C2 (ru) | 2011-02-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9440992B2 (en) | 5,7-disubstituted thiazolo[4,5-D]pyrimidines as chemokine inhibitors | |
| RU2411245C9 (ru) | Новые производные 5,7-дизамещенного [1,3] тиазоло[4,5-d]пиримидин-2(3h)-она | |
| RU2437889C2 (ru) | НОВЫЕ 5,7-ДИЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ [1,3]ТИАЗОЛО[4,5-d]ПИРИМИДИН-2-(3Н)-АМИНА И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ | |
| US7960395B2 (en) | 5,7-disubstituted thiazolo[4,5-d]pyrimidines for the selective inhibition of chemokine receptors | |
| HK1131389B (en) | Novel 5, 7-disubstituted [1, 3]thiazolo [4, 5-d]pyrimidin-2 (3h)-one derivatives and their use in therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TH4A | Reissue of patent specification | ||
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20130404 |