DE60007768T2 - Neue thiazolo(4,5-d)pyrimidinverbindungen - Google Patents

Info

Publication number

DE60007768T2

DE60007768T2 DE60007768T DE60007768T DE60007768T2 DE 60007768 T2 DE60007768 T2 DE 60007768T2 DE 60007768 T DE60007768 T DE 60007768T DE 60007768 T DE60007768 T DE 60007768T DE 60007768 T2 DE60007768 T2 DE 60007768T2

Authority

DE

Germany

Prior art keywords

amino

thio

thiazolo

methyl

pyrimidin

Prior art date

1999-10-01

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

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• YWBULOYFCXZCGF-UHFFFAOYSA-N [1,3]thiazolo[4,5-d]pyrimidine Chemical class C1=NC=C2SC=NC2=N1 YWBULOYFCXZCGF-UHFFFAOYSA-N 0.000 title 1
• -1 thiazolopyrimidine compounds Chemical class 0.000 claims abstract description 69
• 150000003839 salts Chemical class 0.000 claims abstract description 37
• 239000012453 solvate Substances 0.000 claims abstract description 29
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
• 201000010099 disease Diseases 0.000 claims abstract description 25
• 102000019034 Chemokines Human genes 0.000 claims abstract description 12
• 108010012236 Chemokines Proteins 0.000 claims abstract description 12
• 238000000034 method Methods 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
• 238000002360 preparation method Methods 0.000 claims abstract description 5
• 230000001404 mediated effect Effects 0.000 claims abstract description 4
• 150000001875 compounds Chemical class 0.000 claims description 249
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 88
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 74
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
• 239000000203 mixture Substances 0.000 claims description 63
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
• 125000005843 halogen group Chemical group 0.000 claims description 19
• 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 16
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 238000011282 treatment Methods 0.000 claims description 9
• 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 8
• 102000002791 Interleukin-8B Receptors Human genes 0.000 claims description 8
• 108010018951 Interleukin-8B Receptors Proteins 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 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 7
• 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 7
• 102000009410 Chemokine receptor Human genes 0.000 claims description 7
• 108050000299 Chemokine receptor Proteins 0.000 claims description 7
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 7
• 125000001072 heteroaryl group Chemical group 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 6
• 229910052757 nitrogen Inorganic materials 0.000 claims description 6
• 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 claims description 5
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
• 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 claims description 5
• 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 claims description 5
• 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 description 5
• 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 5
• LTLYZBYGTQOYBR-UHFFFAOYSA-N 5-benzylsulfanyl-7-[(1-hydroxy-2-methylpropan-2-yl)amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(NC(C)(CO)C)=NC=1SCC1=CC=CC=C1 LTLYZBYGTQOYBR-UHFFFAOYSA-N 0.000 claims description 5
• VNUFOKWSYSXHCN-LLVKDONJSA-N 5-benzylsulfanyl-7-[[(2r)-1-hydroxybutan-2-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound N=1C=2NC(=O)SC=2C(N[C@@H](CO)CC)=NC=1SCC1=CC=CC=C1 VNUFOKWSYSXHCN-LLVKDONJSA-N 0.000 claims description 5
• UAPAJJYRMYFRNG-UHFFFAOYSA-N 7-[(1-hydroxy-2-methylpropan-2-yl)amino]-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(C)(C)CO)N=2)=C1 UAPAJJYRMYFRNG-UHFFFAOYSA-N 0.000 claims description 5
• 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 description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 239000002253 acid Substances 0.000 claims description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 5
• 125000002837 carbocyclic group Chemical group 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• SJDVXUPTVOUOQW-SBSPUUFOSA-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;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=2NC(=O)SC=2C(N[C@@H](CNCCO)C)=NC=1SCC1=CC=CC(F)=C1F SJDVXUPTVOUOQW-SBSPUUFOSA-N 0.000 claims description 4
• 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 claims description 4
• SASYIPPCKQWLES-NXEZZACHSA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(3r,4r)-4-hydroxypyrrolidin-3-yl]amino]-3h-[1,3]thiazolo[4,5-d]pyrimidin-2-one Chemical compound O[C@@H]1CNC[C@H]1NC1=NC(SCC=2C(=C(F)C=CC=2)F)=NC2=C1SC(=O)N2 SASYIPPCKQWLES-NXEZZACHSA-N 0.000 claims description 4
• 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 4
• 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 description 4
• IEEKYSFSZYAOSV-SBSPUUFOSA-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;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1C=2NC(=O)SC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=C(OCCN)C(Cl)=C1 IEEKYSFSZYAOSV-SBSPUUFOSA-N 0.000 claims description 4
• 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 description 4
• 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 description 4
• 239000000654 additive Substances 0.000 claims description 4
• 230000000996 additive effect Effects 0.000 claims description 4
• 150000004703 alkoxides Chemical class 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 229910052751 metal Inorganic materials 0.000 claims description 4
• 239000002184 metal Substances 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 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 3
• JOWWEOSPWCYGIA-OGFXRTJISA-N 5-[(2,3-difluorophenyl)methylsulfanyl]-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(F)=C1F JOWWEOSPWCYGIA-OGFXRTJISA-N 0.000 claims description 3
• 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
• KHTUORKUWBDRBX-SSDOTTSWSA-N 5-[(3-chloro-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(Cl)=C1F KHTUORKUWBDRBX-SSDOTTSWSA-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
• 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 3
• 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 claims description 3
• 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 3
• 206010028980 Neoplasm Diseases 0.000 claims description 3
• SODPWEYTHUJKHH-OGFXRTJISA-N [Na].ClC=1C(=C(C=CC1)CSC=1N=C(C2=C(N1)NC(S2)=O)N[C@@H](CO)C)F Chemical compound [Na].ClC=1C(=C(C=CC1)CSC=1N=C(C2=C(N1)NC(S2)=O)N[C@@H](CO)C)F SODPWEYTHUJKHH-OGFXRTJISA-N 0.000 claims description 3
• 230000033115 angiogenesis Effects 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 229910052760 oxygen Inorganic materials 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 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
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
• 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 claims description 2
• 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 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
• 108091008928 CXC chemokine receptors Proteins 0.000 claims description 2
• 102000054900 CXCR Receptors Human genes 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims description 2
• 210000001035 gastrointestinal tract Anatomy 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
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 150000003573 thiols Chemical class 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
• 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 1
• 208000027866 inflammatory disease Diseases 0.000 claims 1
• 239000000543 intermediate Substances 0.000 abstract description 4
• 239000000047 product Substances 0.000 description 188
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 90
• 238000005481 NMR spectroscopy Methods 0.000 description 64
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
• 239000000243 solution Substances 0.000 description 55
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
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