NO327706B1 - Nye tiazolo-(4,5-D)pyrimidinforbindelser, fremgangsmate for fremstilling derav, farmasoytisk preparat og mellomprodukter - Google Patents
Nye tiazolo-(4,5-D)pyrimidinforbindelser, fremgangsmate for fremstilling derav, farmasoytisk preparat og mellomprodukter Download PDFInfo
- Publication number
- NO327706B1 NO327706B1 NO20021448A NO20021448A NO327706B1 NO 327706 B1 NO327706 B1 NO 327706B1 NO 20021448 A NO20021448 A NO 20021448A NO 20021448 A NO20021448 A NO 20021448A NO 327706 B1 NO327706 B1 NO 327706B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- thio
- thiazolo
- methyl
- pyrimidin
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 132
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 9
- YWBULOYFCXZCGF-UHFFFAOYSA-N [1,3]thiazolo[4,5-d]pyrimidine Chemical class C1=NC=C2SC=NC2=N1 YWBULOYFCXZCGF-UHFFFAOYSA-N 0.000 title description 4
- 239000012450 pharmaceutical intermediate Substances 0.000 title 1
- -1 thiazolopyrimidine compounds Chemical class 0.000 claims abstract description 80
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 209
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 195
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 160
- 150000001875 compounds Chemical class 0.000 claims description 129
- 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 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 41
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 7
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 6
- UOTNDJLTGMQKQJ-UHFFFAOYSA-N 5-benzylsulfanyl-7-(1,3-dihydroxypropan-2-ylamino)-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(NC(CO)CO)=NC=1SCC1=CC=CC=C1 UOTNDJLTGMQKQJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- ZZAOLDVNKJEEFU-SECBINFHSA-N 5-benzylsulfanyl-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC=C1 ZZAOLDVNKJEEFU-SECBINFHSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
- JAWOJSJRFJRARW-SECBINFHSA-N 5-[(2-fluoro-3-methylphenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC(C)=C1F JAWOJSJRFJRARW-SECBINFHSA-N 0.000 claims description 4
- TWOSSKNCQTVCBF-SECBINFHSA-N 7-[[(2r)-1-hydroxypropan-2-yl]amino]-5-[(2-methoxyphenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound COC1=CC=CC=C1CSC1=NC(N[C@H](C)CO)=C(SC(=O)N2)C2=N1 TWOSSKNCQTVCBF-SECBINFHSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- USASATGXKMVQSJ-SECBINFHSA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(3r)-pyrrolidin-3-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound FC1=CC=CC(CSC=2N=C3NC(=O)SC3=C(N[C@H]3CNCC3)N=2)=C1F USASATGXKMVQSJ-SECBINFHSA-N 0.000 claims description 3
- WVJACUIEKAMQLX-UHFFFAOYSA-N 5-benzylsulfanyl-7-(1,3-dihydroxypropan-2-ylamino)-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one;sodium Chemical compound [Na].N=1C=2NC(=O)SC=2C(NC(CO)CO)=NC=1SCC1=CC=CC=C1 WVJACUIEKAMQLX-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- QNKPNNVLROGERL-UHFFFAOYSA-N 2-[(5-benzylsulfanyl-2-bromo-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-2-methylpropan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(NC(C)(CO)C)=NC=1SCC1=CC=CC=C1 QNKPNNVLROGERL-UHFFFAOYSA-N 0.000 claims description 2
- JZKUVWGFDUVZJW-UHFFFAOYSA-N 2-[[2-bromo-5-[(2,3-difluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-2-methylpropan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(NC(C)(CO)C)=NC=1SCC1=CC=CC(F)=C1F JZKUVWGFDUVZJW-UHFFFAOYSA-N 0.000 claims description 2
- JPKFBTRMHVXMHW-SSDOTTSWSA-N 5-(furan-2-ylmethylsulfanyl)-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CO1 JPKFBTRMHVXMHW-SSDOTTSWSA-N 0.000 claims description 2
- UHMOZGMZLPTSJS-SECBINFHSA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(2r)-1-(2-hydroxyethylamino)propan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CNCCO)C)=NC=1SCC1=CC=CC(F)=C1F UHMOZGMZLPTSJS-SECBINFHSA-N 0.000 claims description 2
- HIZVSVRSJSSQMG-SECBINFHSA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(2r)-1-(dimethylamino)propan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CN(C)C)C)=NC=1SCC1=CC=CC(F)=C1F HIZVSVRSJSSQMG-SECBINFHSA-N 0.000 claims description 2
- SRHSMXLXWORYJK-SSDOTTSWSA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC(F)=C1F SRHSMXLXWORYJK-SSDOTTSWSA-N 0.000 claims description 2
- QBTGEPDYFFOCND-MRVPVSSYSA-N 5-[(2-fluorophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC=C1F QBTGEPDYFFOCND-MRVPVSSYSA-N 0.000 claims description 2
- TVDVXORBNPMAJG-SSDOTTSWSA-N 5-[[3-chloro-4-(trifluoromethoxy)phenyl]methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=C(OC(F)(F)F)C(Cl)=C1 TVDVXORBNPMAJG-SSDOTTSWSA-N 0.000 claims description 2
- TVHSMNAABRNPGB-SSDOTTSWSA-N 7-[[(2r)-1-aminopropan-2-yl]amino]-5-[(2,3-difluorophenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CN)C)=NC=1SCC1=CC=CC(F)=C1F TVHSMNAABRNPGB-SSDOTTSWSA-N 0.000 claims description 2
- YLXVFLMWPWAHHW-OGFXRTJISA-N 7-[[(2r)-1-aminopropan-2-yl]amino]-5-[(2,3-difluorophenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=2NC(=O)SC=2C(N[C@@H](CN)C)=NC=1SCC1=CC=CC(F)=C1F YLXVFLMWPWAHHW-OGFXRTJISA-N 0.000 claims description 2
- ORGFQCQOGOUYCK-SSDOTTSWSA-N 7-[[(2r)-1-aminopropan-2-yl]amino]-5-[(3-chloro-2-fluorophenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CN)C)=NC=1SCC1=CC=CC(Cl)=C1F ORGFQCQOGOUYCK-SSDOTTSWSA-N 0.000 claims description 2
- ISFOBCIXBZKFPN-SNVBAGLBSA-N 7-[[(2r)-1-hydroxypropan-2-yl]amino]-5-(2-phenoxyethylsulfanyl)-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)C)=NC=1SCCOC1=CC=CC=C1 ISFOBCIXBZKFPN-SNVBAGLBSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 229910044991 metal oxide Inorganic materials 0.000 claims description 2
- 150000004706 metal oxides Chemical class 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- LNVWKEXPRCZTSC-UHFFFAOYSA-N [Na].S1C(NC=2N=CN=CC21)=O Chemical compound [Na].S1C(NC=2N=CN=CC21)=O LNVWKEXPRCZTSC-UHFFFAOYSA-N 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- XSNYHNGQBOGSTG-GSVOUGTGSA-N 5-(5-chlorothiadiazol-4-yl)sulfanyl-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SC=1N=NSC=1Cl XSNYHNGQBOGSTG-GSVOUGTGSA-N 0.000 claims 1
- HYELKKZFIXTAEI-MRVPVSSYSA-N 5-[(3-chlorophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC(Cl)=C1 HYELKKZFIXTAEI-MRVPVSSYSA-N 0.000 claims 1
- RAIAMDPHERMZAY-SECBINFHSA-N 5-[[4-(2-aminoethoxy)-3-chlorophenyl]methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=C(OCCN)C(Cl)=C1 RAIAMDPHERMZAY-SECBINFHSA-N 0.000 claims 1
- PRBKDCNAQFLWBK-UHFFFAOYSA-N 7-(1,3-dihydroxypropan-2-ylamino)-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound S1C(C)=NC(CSC=2N=C3NC(=O)SC3=C(NC(CO)CO)N=2)=C1 PRBKDCNAQFLWBK-UHFFFAOYSA-N 0.000 claims 1
- DHADDJPONJRPDC-UHFFFAOYSA-N 7-[(1-hydroxy-2-methylpropan-2-yl)amino]-5-[(2-methylphenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound CC1=CC=CC=C1CSC1=NC(NC(C)(C)CO)=C(SC(=O)N2)C2=N1 DHADDJPONJRPDC-UHFFFAOYSA-N 0.000 claims 1
- KFHSDCXNOPXKDP-ZCFIWIBFSA-N 7-[[(2r)-1-hydroxypropan-2-yl]amino]-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CSC(C)=N1 KFHSDCXNOPXKDP-ZCFIWIBFSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 10
- 102000019034 Chemokines Human genes 0.000 abstract description 7
- 108010012236 Chemokines Proteins 0.000 abstract description 7
- 239000000543 intermediate Substances 0.000 abstract description 5
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract 2
- 239000000047 product Substances 0.000 description 186
- 238000004949 mass spectrometry Methods 0.000 description 162
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- 238000005481 NMR spectroscopy Methods 0.000 description 62
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 33
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 31
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 29
- 229940044613 1-propanol Drugs 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 27
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 10
- 206010039083 rhinitis Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 9
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 8
- 229940035437 1,3-propanediol Drugs 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 8
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 102000002791 Interleukin-8B Receptors Human genes 0.000 description 5
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 5
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 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 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- 108090001007 Interleukin-8 Proteins 0.000 description 4
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 4
- 229950005228 bromoform Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 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 4
- 229940096397 interleukin-8 Drugs 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229960005335 propanol Drugs 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000003643 water by type Substances 0.000 description 4
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 3
- SOXZOCWUQRINNR-UHFFFAOYSA-N (3-chloro-2-fluorophenyl)methanethiol Chemical compound FC1=C(Cl)C=CC=C1CS SOXZOCWUQRINNR-UHFFFAOYSA-N 0.000 description 3
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 108010001478 Bacitracin Proteins 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 102000009410 Chemokine receptor Human genes 0.000 description 3
- 108050000299 Chemokine receptor Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 229960003071 bacitracin Drugs 0.000 description 3
- 229930184125 bacitracin Natural products 0.000 description 3
- 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 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 3
- 239000000706 filtrate Substances 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
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
- 229940116357 potassium thiocyanate Drugs 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- ATTHPHKTDGQZSV-UHFFFAOYSA-N (3-chloro-4-methoxyphenyl)methanethiol Chemical compound COC1=CC=C(CS)C=C1Cl ATTHPHKTDGQZSV-UHFFFAOYSA-N 0.000 description 2
- HYILLTADABKYHO-UHFFFAOYSA-N 1-(bromomethyl)-3-chloro-2-fluorobenzene Chemical compound FC1=C(Cl)C=CC=C1CBr HYILLTADABKYHO-UHFFFAOYSA-N 0.000 description 2
- NPDIDUXTRAITDE-UHFFFAOYSA-N 1-methyl-3-phenylbenzene Chemical group CC1=CC=CC(C=2C=CC=CC=2)=C1 NPDIDUXTRAITDE-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- RVGKWWWCCYFUBP-SSDOTTSWSA-N 7-[[(2r)-1-hydroxypropan-2-yl]amino]-5-(thiophen-2-ylmethylsulfanyl)-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CS1 RVGKWWWCCYFUBP-SSDOTTSWSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-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
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 2
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 2
- 101001069921 Homo sapiens Growth-regulated alpha protein Proteins 0.000 description 2
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000721454 Pemphigus Species 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102100036154 Platelet basic protein Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- CXBFPLGYOUJUKC-UHFFFAOYSA-N [1,3]thiazolo[4,5-d]pyrimidin-2-amine Chemical compound C1=NC=C2SC(N)=NC2=N1 CXBFPLGYOUJUKC-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 108010035886 connective tissue-activating peptide Proteins 0.000 description 2
- 108010004073 cysteinylcysteine Proteins 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000012536 storage buffer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- PJUDFYDAJBQPEA-UHFFFAOYSA-N (2-methylphenyl)methanethiol Chemical compound CC1=CC=CC=C1CS PJUDFYDAJBQPEA-UHFFFAOYSA-N 0.000 description 1
- LCRPHMIXJBFWKS-LLVKDONJSA-N (2r)-2-[(5-benzylsulfanyl-2-bromo-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]butan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(N[C@@H](CO)CC)=NC=1SCC1=CC=CC=C1 LCRPHMIXJBFWKS-LLVKDONJSA-N 0.000 description 1
- YOMMMPLAOTYUGI-GFCCVEGCSA-N (2r)-2-[(5-benzylsulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]butan-1-ol Chemical compound N=1C=2N=C(OC)SC=2C(N[C@@H](CO)CC)=NC=1SCC1=CC=CC=C1 YOMMMPLAOTYUGI-GFCCVEGCSA-N 0.000 description 1
- ASGKXARWNJBFGZ-SNVBAGLBSA-N (2r)-2-[[2-amino-5-(2-phenoxyethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CO)C)=NC=1SCCOC1=CC=CC=C1 ASGKXARWNJBFGZ-SNVBAGLBSA-N 0.000 description 1
- OBYWIJUSWOOFRB-SECBINFHSA-N (2r)-2-[[2-amino-5-[(2-fluoro-3-methylphenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(C)=C1F OBYWIJUSWOOFRB-SECBINFHSA-N 0.000 description 1
- CKTZOYIABCTUGQ-SECBINFHSA-N (2r)-2-[[2-bromo-5-[(2-fluoro-3-methylphenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(C)=C1F CKTZOYIABCTUGQ-SECBINFHSA-N 0.000 description 1
- XGMBSVRWDHOKTC-ZCFIWIBFSA-N (2r)-2-[[2-bromo-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol Chemical compound N=1C=2N=C(Br)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CSC(C)=N1 XGMBSVRWDHOKTC-ZCFIWIBFSA-N 0.000 description 1
- HGEOFKLNVHADCC-SSDOTTSWSA-N (2r)-2-[[2-methoxy-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol Chemical compound N=1C(N[C@H](C)CO)=C2SC(OC)=NC2=NC=1SCC1=CSC(C)=N1 HGEOFKLNVHADCC-SSDOTTSWSA-N 0.000 description 1
- JCBPETKZIGVZRE-SCSAIBSYSA-N (2r)-2-aminobutan-1-ol Chemical compound CC[C@@H](N)CO JCBPETKZIGVZRE-SCSAIBSYSA-N 0.000 description 1
- HQMLIDZJXVVKCW-UWTATZPHSA-N (2r)-2-aminopropanamide Chemical compound C[C@@H](N)C(N)=O HQMLIDZJXVVKCW-UWTATZPHSA-N 0.000 description 1
- FIAINKIUSZGVGX-HSHFZTNMSA-N (2r)-2-aminopropanamide;hydrochloride Chemical compound Cl.C[C@@H](N)C(N)=O FIAINKIUSZGVGX-HSHFZTNMSA-N 0.000 description 1
- GCRAJGXUVOIRFN-QMMMGPOBSA-N (2s)-2-[[2-amino-5-[(2,3-difluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-3-hydroxypropanamide Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CO)C(=O)N)=NC=1SCC1=CC=CC(F)=C1F GCRAJGXUVOIRFN-QMMMGPOBSA-N 0.000 description 1
- RXIOKASMRGDOPE-QMMMGPOBSA-N (2s)-2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2-oxo-3h-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-3-hydroxypropanamide Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)C(=O)N)=NC=1SCC1=CC=CC(F)=C1F RXIOKASMRGDOPE-QMMMGPOBSA-N 0.000 description 1
- CJTZBMZKOSSBLN-SNVBAGLBSA-N (3r)-3-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]pyrrolidine-1-carboxylic acid Chemical compound N=1C(N[C@H]2CN(CC2)C(O)=O)=C2SC(OC)=NC2=NC=1SCC1=CC=CC(F)=C1F CJTZBMZKOSSBLN-SNVBAGLBSA-N 0.000 description 1
- NWAVZGZOENKEJV-UHFFFAOYSA-N (6-amino-2-benzylsulfanyl-4-oxo-1h-pyrimidin-5-yl) thiocyanate Chemical compound O=C1C(SC#N)=C(N)NC(SCC=2C=CC=CC=2)=N1 NWAVZGZOENKEJV-UHFFFAOYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- FTBSGSZZESQDBM-UHFFFAOYSA-N 1-(bromomethyl)-2,3-difluorobenzene Chemical compound FC1=CC=CC(CBr)=C1F FTBSGSZZESQDBM-UHFFFAOYSA-N 0.000 description 1
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 1
- LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- BHWJMPDCCDMCKC-UHFFFAOYSA-N 1-methyl-2-methylsulfanylbenzene Chemical compound CSC1=CC=CC=C1C BHWJMPDCCDMCKC-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- LOUODJGOYJHXPS-UHFFFAOYSA-N 1h-pyrimidin-2-one;sodium Chemical compound [Na].OC1=NC=CC=N1 LOUODJGOYJHXPS-UHFFFAOYSA-N 0.000 description 1
- GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 1
- DHFRSTCPYRRWCN-UHFFFAOYSA-N 2-(2-chloro-4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1Cl DHFRSTCPYRRWCN-UHFFFAOYSA-N 0.000 description 1
- ZFFTZDQKIXPDAF-UHFFFAOYSA-N 2-Furanmethanethiol Chemical compound SCC1=CC=CO1 ZFFTZDQKIXPDAF-UHFFFAOYSA-N 0.000 description 1
- OILNBNYEAQZAHJ-UHFFFAOYSA-N 2-[(5-benzylsulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-2-methylpropan-1-ol Chemical compound N=1C(NC(C)(C)CO)=C2SC(OC)=NC2=NC=1SCC1=CC=CC=C1 OILNBNYEAQZAHJ-UHFFFAOYSA-N 0.000 description 1
- IJGLPKPKWBBZCJ-UHFFFAOYSA-N 2-[(5-benzylsulfanyl-2-methoxy-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]propane-1,3-diol Chemical compound N=1C(NC(CO)CO)=C2SC(OC)=NC2=NC=1SCC1=CC=CC=C1 IJGLPKPKWBBZCJ-UHFFFAOYSA-N 0.000 description 1
- RPVZYCYGELSQGJ-UHFFFAOYSA-N 2-[2-chloro-4-(hydroxymethyl)phenoxy]acetamide Chemical compound NC(=O)COC1=CC=C(CO)C=C1Cl RPVZYCYGELSQGJ-UHFFFAOYSA-N 0.000 description 1
- BUYQATSMBDWCCZ-UHFFFAOYSA-N 2-[[2-bromo-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propane-1,3-diol Chemical compound S1C(C)=NC(CSC=2N=C3N=C(Br)SC3=C(NC(CO)CO)N=2)=C1 BUYQATSMBDWCCZ-UHFFFAOYSA-N 0.000 description 1
- JEXKANXETOIMOM-UHFFFAOYSA-N 2-[[2-methoxy-5-[(2-methyl-1,3-thiazol-4-yl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-2-methylpropan-1-ol Chemical compound N=1C(NC(C)(C)CO)=C2SC(OC)=NC2=NC=1SCC1=CSC(C)=N1 JEXKANXETOIMOM-UHFFFAOYSA-N 0.000 description 1
- MCGDCISQNDQHDK-UHFFFAOYSA-N 2-amino-5-sulfanylidene-4h-[1,3]thiazolo[4,5-d]pyrimidin-7-one Chemical compound N1C(=S)NC(=O)C2=C1N=C(N)S2 MCGDCISQNDQHDK-UHFFFAOYSA-N 0.000 description 1
- VGSOCYWCRMXQAB-UHFFFAOYSA-N 3-chloro-4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1Cl VGSOCYWCRMXQAB-UHFFFAOYSA-N 0.000 description 1
- UXRJWVPEEFHONQ-UHFFFAOYSA-N 3-methyl-4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1C UXRJWVPEEFHONQ-UHFFFAOYSA-N 0.000 description 1
- ILAXZPDKSKVBRP-UHFFFAOYSA-N 4h-[1,3]thiazolo[4,5-d]pyrimidin-7-one Chemical compound O=C1N=CNC2=C1SC=N2 ILAXZPDKSKVBRP-UHFFFAOYSA-N 0.000 description 1
- UEOGZKUCSJWEMN-KLQYNRQASA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(3r)-pyrrolidin-3-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one;dihydrochloride Chemical compound Cl.Cl.FC1=CC=CC(CSC=2N=C3NC(=O)SC3=C(N[C@H]3CNCC3)N=2)=C1F UEOGZKUCSJWEMN-KLQYNRQASA-N 0.000 description 1
- UNAPJJXKKZBXIV-MRVPVSSYSA-N 5-[(2-bromophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC=C1Br UNAPJJXKKZBXIV-MRVPVSSYSA-N 0.000 description 1
- XLRFVVJZXSLMOK-MRVPVSSYSA-N 5-[(3-bromophenyl)methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC(Br)=C1 XLRFVVJZXSLMOK-MRVPVSSYSA-N 0.000 description 1
- PPAMCZZUMFQNPN-SSDOTTSWSA-N 5-[[2-fluoro-3-(trifluoromethyl)phenyl]methylsulfanyl]-7-[[(2r)-1-hydroxypropan-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)C)=NC=1SCC1=CC=CC(C(F)(F)F)=C1F PPAMCZZUMFQNPN-SSDOTTSWSA-N 0.000 description 1
- UQBWEMSONKYVSP-SBSPUUFOSA-N 5-benzylsulfanyl-7-[[(2r)-1-hydroxypropan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one;sodium Chemical compound [Na].N=1C=2NC(=O)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC=C1 UQBWEMSONKYVSP-SBSPUUFOSA-N 0.000 description 1
- DADXWROZAWLOFB-UHFFFAOYSA-N 5-chloro-4-(chloromethyl)thiadiazole Chemical compound ClCC=1N=NSC=1Cl DADXWROZAWLOFB-UHFFFAOYSA-N 0.000 description 1
- USCKGDQJCBTIGK-UHFFFAOYSA-N 6-amino-2-benzylsulfanyl-1h-pyrimidin-4-one Chemical compound N1C(N)=CC(=O)N=C1SCC1=CC=CC=C1 USCKGDQJCBTIGK-UHFFFAOYSA-N 0.000 description 1
- CMXFFNQBVIOLNG-UHFFFAOYSA-N 7-chloro-5-[(2,3-difluorophenyl)methylsulfanyl]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound FC1=CC=CC(CSC=2N=C3NC(=O)SC3=C(Cl)N=2)=C1F CMXFFNQBVIOLNG-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000035939 Alveolitis allergic Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 201000008283 Atrophic Rhinitis 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
- 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
- 102100025074 C-C chemokine receptor-like 2 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
- 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
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 1
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 108091008928 CXC chemokine receptors Proteins 0.000 description 1
- 102000054900 CXCR Receptors Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- YMFOTDXCWLLGTH-UHFFFAOYSA-N FC(C(=O)O)(F)F.S1C(NC=2N=CN=CC21)=O Chemical compound FC(C(=O)O)(F)F.S1C(NC=2N=CN=CC21)=O YMFOTDXCWLLGTH-UHFFFAOYSA-N 0.000 description 1
- 208000027445 Farmer Lung Diseases 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000282412 Homo Species 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
- 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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 241001502129 Mullus Species 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- GVHIYWUSARFOOK-UHFFFAOYSA-N O.NC1=NC(=NC(=C1)O)S.NC1=CC(NC(=N1)SCC=1N=C(SC1)C)=O Chemical compound O.NC1=NC(=NC(=C1)O)S.NC1=CC(NC(=N1)SCC=1N=C(SC1)C)=O GVHIYWUSARFOOK-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010060932 Postoperative adhesion Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 206010039088 Rhinitis atrophic Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047112 Vasculitides Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 1
- ZHWWPRBSUHITHG-GSVOUGTGSA-N [(2r)-1-aminopropan-2-yl]carbamic acid Chemical compound NC[C@@H](C)NC(O)=O ZHWWPRBSUHITHG-GSVOUGTGSA-N 0.000 description 1
- YVAFZQNFXYSIAT-GFCCVEGCSA-N [(2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propyl]carbamic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CNC(O)=O)C)C3=CC=CC=C3C2=C1 YVAFZQNFXYSIAT-GFCCVEGCSA-N 0.000 description 1
- UFCRFQPOIKCJFK-SECBINFHSA-N [(2r)-2-[(2-amino-5-benzylsulfonyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]propyl]carbamic acid Chemical compound N=1C=2N=C(N)SC=2C(N[C@@H](CNC(O)=O)C)=NC=1S(=O)(=O)CC1=CC=CC=C1 UFCRFQPOIKCJFK-SECBINFHSA-N 0.000 description 1
- BPLAGHPHSJBKQR-UHFFFAOYSA-N [2-fluoro-3-(trifluoromethyl)phenyl]methanethiol Chemical compound FC1=C(CS)C=CC=C1C(F)(F)F BPLAGHPHSJBKQR-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000022195 farmer lung disease Diseases 0.000 description 1
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- QHDRKFYEGYYIIK-UHFFFAOYSA-N isovaleronitrile Chemical compound CC(C)CC#N QHDRKFYEGYYIIK-UHFFFAOYSA-N 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 208000008585 mastocytosis Diseases 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
- 229960003194 meglumine Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- GCDZDXVTDCMNMN-UHFFFAOYSA-N n-(2-aminoethyl)methanesulfonamide Chemical compound CS(=O)(=O)NCCN GCDZDXVTDCMNMN-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- KBJXDTIYSSQJAI-UHFFFAOYSA-N propylcarbamic acid Chemical compound CCCNC(O)=O KBJXDTIYSSQJAI-UHFFFAOYSA-N 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- JCADUCUAODRVLA-UHFFFAOYSA-N s-[[4-(2-amino-2-oxoethoxy)-3-chlorophenyl]methyl] ethanethioate Chemical compound CC(=O)SCC1=CC=C(OCC(N)=O)C(Cl)=C1 JCADUCUAODRVLA-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- MOZOQDNRVPHFOO-RNFRBKRXSA-N tert-butyl (3r,4r)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](N)[C@H](O)C1 MOZOQDNRVPHFOO-RNFRBKRXSA-N 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- GCZQHDFWKVMZOE-UHFFFAOYSA-N thiophen-2-ylmethanethiol Chemical compound SCC1=CC=CS1 GCZQHDFWKVMZOE-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive 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
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903544A SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Novel compounds |
| PCT/GB2000/003692 WO2001025242A1 (en) | 1999-10-01 | 2000-09-26 | Novel thiazolo(4,5-d)pyrimidine compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20021448D0 NO20021448D0 (no) | 2002-03-22 |
| NO20021448L NO20021448L (no) | 2002-05-22 |
| NO327706B1 true NO327706B1 (no) | 2009-09-14 |
Family
ID=20417218
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20021448A NO327706B1 (no) | 1999-10-01 | 2002-03-22 | Nye tiazolo-(4,5-D)pyrimidinforbindelser, fremgangsmate for fremstilling derav, farmasoytisk preparat og mellomprodukter |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US6790850B1 (ru) |
| EP (2) | EP1222195B1 (ru) |
| JP (1) | JP4824889B2 (ru) |
| KR (1) | KR100765051B1 (ru) |
| CN (1) | CN1210279C (ru) |
| AT (2) | ATE384068T1 (ru) |
| AU (1) | AU777872B2 (ru) |
| BR (1) | BR0014334A (ru) |
| CA (1) | CA2385269C (ru) |
| CZ (1) | CZ20021113A3 (ru) |
| DE (2) | DE60007768T2 (ru) |
| DK (1) | DK1222195T3 (ru) |
| EE (1) | EE05037B1 (ru) |
| ES (2) | ES2213043T3 (ru) |
| HK (1) | HK1052009A1 (ru) |
| HU (1) | HUP0204246A3 (ru) |
| IL (2) | IL148910A0 (ru) |
| IS (1) | IS2229B (ru) |
| MX (1) | MXPA02003263A (ru) |
| NO (1) | NO327706B1 (ru) |
| NZ (1) | NZ517880A (ru) |
| PT (1) | PT1222195E (ru) |
| SE (1) | SE9903544D0 (ru) |
| TW (1) | TWI260324B (ru) |
| UA (1) | UA73521C2 (ru) |
| WO (1) | WO2001025242A1 (ru) |
| ZA (1) | ZA200202380B (ru) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9903544D0 (sv) * | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| ATE255584T1 (de) * | 2000-02-11 | 2003-12-15 | Astrazeneca Ab | Pyrimidinverbindungen und ihre verwendung als modulatoren der chemokin-rezeptor-aktivität |
| GB2359078A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359551A (en) * | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| SE0101322D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| SE0102716D0 (sv) * | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
| JP4464136B2 (ja) | 2001-12-06 | 2010-05-19 | メルク・シャープ・エンド・ドーム・コーポレイション | 有糸分裂キネシン阻害薬 |
| JP4467979B2 (ja) | 2001-12-06 | 2010-05-26 | メルク・シャープ・エンド・ドーム・コーポレイション | 有糸分裂キネシン阻害剤 |
| GB0217431D0 (en) * | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| KR20050067383A (ko) | 2002-08-06 | 2005-07-01 | 아스트라제네카 아베 | Ｔｉｅ2(ｔｅｋ) 활성을 갖는 축합 피리딘 및 피리미딘 |
| DE60318219T2 (de) | 2002-08-24 | 2009-01-15 | Astrazeneca Ab | PYRIMIDINDERIVATE ALS MODULATOREN DER AKTIVITuT VON CHEMOKINREZEPTOREN |
| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221828D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| KR20060120014A (ko) * | 2003-10-07 | 2006-11-24 | 아스트라제네카 아베 | 케모킨, 특히 ｃｘ3ｃｒ1 수용체 길항제로서 유용한 신규한2-치환된 4-아미노-티아졸로[4,5-ｄ]피리미딘 |
| GB0328243D0 (en) * | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| EP1809624B1 (en) | 2004-08-28 | 2013-11-20 | AstraZeneca AB | Pyrimidine sulphonamide derivatives as chemokine receptor modulators |
| JP2008524186A (ja) * | 2004-12-17 | 2008-07-10 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性の調節のためのチアゾロピラミジン化合物 |
| EP1864136A1 (en) * | 2005-03-23 | 2007-12-12 | AstraZeneca AB | Screen |
| UA90707C2 (en) * | 2005-04-06 | 2010-05-25 | Астразенека Аб | Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives |
| AR053347A1 (es) | 2005-04-06 | 2007-05-02 | Astrazeneca Ab | Derivados de [1,3]tiazolo[4,5-d]pirimidin-2(3h)-ona 5,7-sustituidos |
| TW200820973A (en) | 2006-09-29 | 2008-05-16 | Astrazeneca Ab | Novel compounds 480 |
| 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. |
| CN101671336B (zh) | 2009-09-23 | 2013-11-13 | 辽宁利锋科技开发有限公司 | 芳杂环并嘧啶衍生物和类似物及其制备方法和用途 |
| CN101899058B (zh) * | 2010-05-24 | 2012-05-23 | 中国人民解放军第四军医大学 | 一种噻唑并嘧啶化合物及其制备方法和应用 |
| WO2014205127A2 (en) | 2013-06-18 | 2014-12-24 | New York University | Cellular factors involved in the cytotoxicity of staphylococcus aureus leukocidins: novel therapeutic targets |
| EP3027627B1 (en) * | 2013-08-02 | 2018-01-31 | Syntrix Biosystems Inc. | 2-[5-[n-(4-fluorophenyl)carbamoyl]pyrimidin-2-ylsulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid |
| US8969365B2 (en) | 2013-08-02 | 2015-03-03 | Syntrix Biosystems, Inc. | Thiopyrimidinecarboxamides as CXCR1/2 modulators |
| US10561676B2 (en) | 2013-08-02 | 2020-02-18 | Syntrix Biosystems Inc. | Method for treating cancer using dual antagonists of CXCR1 and CXCR2 |
| US10046002B2 (en) | 2013-08-02 | 2018-08-14 | Syntrix Biosystems Inc. | Method for treating cancer using chemokine antagonists |
| WO2018073248A1 (en) | 2016-10-17 | 2018-04-26 | Icm (Institut Du Cerveau Et De La Moelle Épinière) | Prognosis of demyelinating diseases patients and treatment thereof |
| CN110172067B (zh) * | 2019-04-11 | 2021-06-15 | 河南科技大学第一附属医院 | 一种具有杀菌活性的噻唑类药物分子及其制备方法 |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2924472A (en) | 1957-06-27 | 1960-02-09 | Gen Motors Corp | Pipe joint seal |
| GB1009477A (en) | 1962-02-13 | 1965-11-10 | Smith Kline French Lab | Novel process for preparing heterocyclic compounds |
| US3182062A (en) | 1962-02-28 | 1965-05-04 | Smith Kline French Lab | Synthesis of quinoxalines and analogues thereof |
| US3318900A (en) | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| BE668603A (ru) | 1964-08-20 | |||
| DE2331223C2 (de) | 1972-06-19 | 1984-11-22 | Kohjin Co., Ltd., Tokio / Tokyo | S-substituierte-2-Thioadenosine, deren 5'-Monophosphate, Verfahren zu deren Herstellung und Arzneimittel, welche diese enthalten |
| US4120521A (en) | 1975-08-28 | 1978-10-17 | Rieber & Son Plastic-Industri A/S | Combined mould element and sealing ring |
| EG12406A (en) | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| GB1600293A (en) | 1977-02-04 | 1981-10-14 | British Oceanics Ltd | Sealing arrangements |
| US4188040A (en) | 1977-04-06 | 1980-02-12 | Firma WOCO Franz-Josef Wolf & Co. | Sealing ring |
| DE2726959A1 (de) | 1977-06-15 | 1979-01-18 | Arlt Christian | Dichteinsatz zum dichten verbinden von zwei rohren |
| FR2421899A1 (fr) | 1978-01-16 | 1979-11-02 | Roussel Uclaf | Nouveaux derives du tetrahydropyridinyl-indole et leurs sels, le procede de preparation et l'application a titre de medicaments de ces nouveaux produits |
| US4410528A (en) | 1980-05-16 | 1983-10-18 | Kyowa Hakko Kogyo Co., Ltd. | Hypotensive piperidine derivatives |
| DE3219522A1 (de) | 1981-10-28 | 1983-12-01 | Denso-Chemie Wedekind Kg, 5090 Leverkusen | Steckmuffendichtung fuer rohre |
| FR2547888B1 (fr) | 1983-06-22 | 1985-12-13 | Sabla Sa | Bague d'etancheite a implants pour tuyaux a emboitement |
| CA1338012C (en) | 1987-04-27 | 1996-01-30 | John Michael Mccall | Pharmaceutically active amines |
| SE8800348L (sv) | 1988-02-03 | 1989-08-04 | Forsheda Ab | Taetningsring och verktyg foer framstaellning daerav |
| FR2659656B1 (fr) | 1990-03-15 | 1994-09-09 | Sanofi Sa | Derives de pyrimidinedione-2,4 et medicaments les contenant. |
| DE4119767A1 (de) * | 1991-06-15 | 1992-12-17 | Dresden Arzneimittel | Verfahren zur herstellung von (pyrimid-2-yl-thio- bzw. seleno)-essigsaeurederivaten |
| US5169161A (en) | 1991-09-19 | 1992-12-08 | Hail Mary Rubber Co., Inc. | Symmetrical gasket for pipe joints |
| DE4134089C2 (de) | 1991-10-15 | 1994-10-13 | Dueker Eisenwerk | Schubgesicherte Muffenverbindung |
| JPH05188994A (ja) | 1992-01-07 | 1993-07-30 | Sony Corp | 騒音抑圧装置 |
| DE4229609C2 (de) | 1992-09-04 | 2003-05-08 | Forsheda Stefa Gmbh | Abdichtung zwischen zwei ineinandersteckbaren Teilen |
| US5521197A (en) | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
| DE69628804T2 (de) * | 1995-12-08 | 2003-12-18 | Pfizer Inc., New York | Substitutierte heterozyclische Derivate als CRF Antagonisten |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| SE515033C2 (sv) | 1995-12-27 | 2001-06-05 | Forsheda Ab | Tätningsanordning |
| KR19990082463A (ko) | 1996-02-13 | 1999-11-25 | 돈 리사 로얄 | 혈관 내피 성장 인자 억제제로서의 퀴나졸린유도체 |
| CN1116286C (zh) | 1996-03-05 | 2003-07-30 | 曾尼卡有限公司 | 4－苯胺基喹唑啉衍生物 |
| AU2388697A (en) | 1996-04-19 | 1997-11-12 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| CN1227554A (zh) * | 1996-08-28 | 1999-09-01 | 辉瑞大药厂 | 取代的6,5－杂二环衍生物 |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| WO1998025617A1 (en) | 1996-12-13 | 1998-06-18 | Merck & Co., Inc. | Substituted aryl piperazines as modulators of chemokine receptor activity |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| JP2002510327A (ja) | 1997-07-25 | 2002-04-02 | メルク エンド カンパニー インコーポレーテッド | 環状アミンケモカイン受容体活性調節剤 |
| AR013669A1 (es) | 1997-10-07 | 2001-01-10 | Smithkline Beecham Corp | Compuestos y metodos |
| NZ504800A (en) | 1997-11-28 | 2001-10-26 | Sumitomo Pharma | 6-Amino-9-benzyl-8-hydroxy-purine derivatives and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases thereof |
| PT1049689E (pt) | 1998-01-19 | 2002-09-30 | Pfizer | Compostos de 4-(2-ceto-1-benzimidazolinil)piperidina como agonistas do receptor orl1 |
| AU747508B2 (en) | 1998-03-19 | 2002-05-16 | Nihon Nohyaku Co., Ltd. | Arylpiperidine derivatives and use thereof |
| AU3213699A (en) * | 1998-04-03 | 1999-10-25 | Du Pont Pharmaceuticals Company | Thiazolo(4,5-d)pyrimidines and pyridines as corticotropin releasing factor (CRF)antagonists |
| MA26659A1 (fr) | 1998-08-06 | 2004-12-20 | Pfizer | Dérivés de benzimidazole nouveaux, compositions pharmaceutiques les contenant et procédé pour leur préparation. |
| SE9802729D0 (sv) * | 1998-08-13 | 1998-08-13 | Astra Pharma Prod | Novel Compounds |
| US5988695A (en) | 1998-08-26 | 1999-11-23 | S&B Technical Products, Inc. | Pipe gasket with embedded ring |
| PE20001420A1 (es) | 1998-12-23 | 2000-12-18 | Pfizer | Moduladores de ccr5 |
| AU770551B2 (en) | 1998-12-28 | 2004-02-26 | 4-Aza Bioscience Nv | Immunosuppressive effects of pteridine derivatives |
| GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
| GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
| EP1187615A2 (en) | 1999-02-02 | 2002-03-20 | K.U. Leuven Research & Development | Immunosurpressive effects of pteridine derivatives |
| US6248755B1 (en) | 1999-04-06 | 2001-06-19 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| US6142484A (en) | 1999-04-15 | 2000-11-07 | Vassallo Research & Development Corporation | Composite multi-pressure gasket |
| US6930101B1 (en) * | 1999-05-17 | 2005-08-16 | The Regents Of The University Of California | Thiazolopyrimidines useful as TNFα inhibitors |
| US6432981B1 (en) | 1999-06-11 | 2002-08-13 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| US6340681B1 (en) | 1999-07-16 | 2002-01-22 | Pfizer Inc | 2-benzimidazolylamine compounds as ORL-1-receptor agonists |
| MXPA02001108A (es) | 1999-09-15 | 2002-08-20 | Warner Lambert Co | Pieridinonas como inhibidores de la cinasa. |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| PE20010628A1 (es) | 1999-10-01 | 2001-06-18 | Takeda Chemical Industries Ltd | Compuestos de amina ciclica, su produccion y su uso |
| DE60023100T2 (de) | 2000-01-05 | 2006-07-06 | Pfizer Inc. | Benzimidazol-Verbindungen zur Verwendung als ORL1-Rezeptor-Antagonisten |
| GB2359079A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359078A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| ATE255584T1 (de) | 2000-02-11 | 2003-12-15 | Astrazeneca Ab | Pyrimidinverbindungen und ihre verwendung als modulatoren der chemokin-rezeptor-aktivität |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB0005642D0 (en) | 2000-03-10 | 2000-05-03 | Astrazeneca Uk Ltd | Chemical compounds |
| WO2001070689A1 (fr) | 2000-03-24 | 2001-09-27 | Meiji Seika Kaisha, Ltd. | DERIVES DE LA DIPHENYLALKYLAMINE UTILES COMME AGONISTES DU RECEPTEUR DE L'OPIOIDE $g(d) |
| IL152682A0 (en) | 2000-05-31 | 2003-06-24 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
| PL359181A1 (en) | 2000-07-07 | 2004-08-23 | Angiogene Pharmaceuticals Limited | Colchinol derivatives as angiogenesis inhibitors |
| CN1255391C (zh) | 2000-07-07 | 2006-05-10 | 安吉奥金尼药品有限公司 | 作为血管破坏剂的colchinol衍生物 |
| SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| SE0004110L (sv) | 2000-11-10 | 2002-05-11 | Forsheda Ab | Tätningsring |
| SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| SE0102716D0 (sv) | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
| GB0221829D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221828D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| KR20060120014A (ko) | 2003-10-07 | 2006-11-24 | 아스트라제네카 아베 | 케모킨, 특히 ｃｘ3ｃｒ1 수용체 길항제로서 유용한 신규한2-치환된 4-아미노-티아졸로[4,5-ｄ]피리미딘 |
| GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| WO2005082865A1 (ja) | 2004-02-27 | 2005-09-09 | Astellas Pharma Inc. | 縮合二環性ピリミジン誘導体 |
| JP2008524186A (ja) | 2004-12-17 | 2008-07-10 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性の調節のためのチアゾロピラミジン化合物 |
-
1999
- 1999-10-01 SE SE9903544A patent/SE9903544D0/xx unknown
-
2000
- 2000-09-26 WO PCT/GB2000/003692 patent/WO2001025242A1/en active IP Right Grant
- 2000-09-26 AU AU73049/00A patent/AU777872B2/en not_active Ceased
- 2000-09-26 NZ NZ517880A patent/NZ517880A/en not_active IP Right Cessation
- 2000-09-26 AT AT03015019T patent/ATE384068T1/de not_active IP Right Cessation
- 2000-09-26 CA CA2385269A patent/CA2385269C/en not_active Expired - Lifetime
- 2000-09-26 UA UA2002032035A patent/UA73521C2/uk unknown
- 2000-09-26 DK DK00960891T patent/DK1222195T3/da active
- 2000-09-26 EP EP00960891A patent/EP1222195B1/en not_active Expired - Lifetime
- 2000-09-26 DE DE60007768T patent/DE60007768T2/de not_active Expired - Lifetime
- 2000-09-26 BR BR0014334-0A patent/BR0014334A/pt not_active IP Right Cessation
- 2000-09-26 JP JP2001528186A patent/JP4824889B2/ja not_active Expired - Fee Related
- 2000-09-26 AT AT00960891T patent/ATE257838T1/de active
- 2000-09-26 EP EP03015019A patent/EP1348709B1/en not_active Expired - Lifetime
- 2000-09-26 EE EEP200200174A patent/EE05037B1/xx not_active IP Right Cessation
- 2000-09-26 KR KR1020027004180A patent/KR100765051B1/ko not_active IP Right Cessation
- 2000-09-26 DE DE60037836T patent/DE60037836T2/de not_active Expired - Lifetime
- 2000-09-26 ES ES00960891T patent/ES2213043T3/es not_active Expired - Lifetime
- 2000-09-26 PT PT00960891T patent/PT1222195E/pt unknown
- 2000-09-26 US US10/089,571 patent/US6790850B1/en not_active Expired - Fee Related
- 2000-09-26 HU HU0204246A patent/HUP0204246A3/hu unknown
- 2000-09-26 ES ES03015019T patent/ES2298451T3/es not_active Expired - Lifetime
- 2000-09-26 MX MXPA02003263A patent/MXPA02003263A/es active IP Right Grant
- 2000-09-26 CZ CZ20021113A patent/CZ20021113A3/cs unknown
- 2000-09-26 CN CNB008163189A patent/CN1210279C/zh not_active Expired - Fee Related
- 2000-09-26 IL IL14891000A patent/IL148910A0/xx active IP Right Grant
- 2000-10-19 TW TW089121952A patent/TWI260324B/zh not_active IP Right Cessation
-
2002
- 2002-03-18 IS IS6306A patent/IS2229B/is unknown
- 2002-03-22 NO NO20021448A patent/NO327706B1/no not_active IP Right Cessation
- 2002-03-25 ZA ZA200202380A patent/ZA200202380B/en unknown
- 2002-03-26 IL IL148910A patent/IL148910A/en not_active IP Right Cessation
-
2003
- 2003-06-17 HK HK03104330A patent/HK1052009A1/xx not_active IP Right Cessation
-
2004
- 2004-06-09 US US10/863,995 patent/US20040224961A1/en not_active Abandoned
-
2009
- 2009-04-29 US US12/432,224 patent/US8143261B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO327706B1 (no) | Nye tiazolo-(4,5-D)pyrimidinforbindelser, fremgangsmate for fremstilling derav, farmasoytisk preparat og mellomprodukter | |
| AU768004B2 (en) | Novel thiazolopyrimidine compounds | |
| US6875868B2 (en) | Pteridine compounds for the treatment of psoriasis | |
| US20050234077A1 (en) | Pyrimidine compounds and their use as modulators of chemokine receptor activity | |
| US20060111569A1 (en) | Thiazolopyrimidines and their use as modulators of chemokine receptor activity | |
| EP1257556B1 (en) | Thiazolopyrimidines and their use as modulators of chemokine receptor activity | |
| PL203572B1 (pl) | Zwi azek tiazolo[4,5-d]pirymidynowy, sposób jego wytwarzania, zwi azki po srednie, srodek farmaceutyczny oraz zastosowanie tego zwi azku |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |