TW200904813A - Compounds - Google Patents

Info

Publication number

TW200904813A

TW200904813A TW097125962A TW97125962A TW200904813A TW 200904813 A TW200904813 A TW 200904813A TW 097125962 A TW097125962 A TW 097125962A TW 97125962 A TW97125962 A TW 97125962A TW 200904813 A TW200904813 A TW 200904813A

Authority

TW

Taiwan

Prior art keywords

alkyl

group

amine

alkoxy

phenyl

Prior art date

2007-07-09

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 83
• 150000003839 salts Chemical class 0.000 claims abstract description 53
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 42
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
• 201000010099 disease Diseases 0.000 claims abstract description 25
• 201000011510 cancer Diseases 0.000 claims abstract description 19
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 230000002062 proliferating effect Effects 0.000 claims abstract description 13
• 238000000034 method Methods 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 1452
• 125000003545 alkoxy group Chemical group 0.000 claims description 501
• -1 nitro, hydroxy Chemical group 0.000 claims description 491
• 150000001412 amines Chemical class 0.000 claims description 354
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 246
• 125000001424 substituent group Chemical group 0.000 claims description 218
• 125000003277 amino group Chemical group 0.000 claims description 177
• 125000000623 heterocyclic group Chemical group 0.000 claims description 168
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 160
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 141
• 125000005843 halogen group Chemical group 0.000 claims description 134
• 229910052739 hydrogen Inorganic materials 0.000 claims description 133
• 239000001257 hydrogen Substances 0.000 claims description 133
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 133
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 120
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 97
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 94
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 85
• 239000000460 chlorine Substances 0.000 claims description 84
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 71
• 125000002837 carbocyclic group Chemical group 0.000 claims description 67
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 59
• 125000003282 alkyl amino group Chemical group 0.000 claims description 58
• 150000003973 alkyl amines Chemical class 0.000 claims description 56
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 56
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 51
• 150000002431 hydrogen Chemical class 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 50
• 229910052799 carbon Inorganic materials 0.000 claims description 46
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 41
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 40
• 125000004432 carbon atom Chemical group C* 0.000 claims description 37
• 150000001721 carbon Chemical group 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 30
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 27
• 125000004076 pyridyl group Chemical group 0.000 claims description 25
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims description 23
• 229960005286 carbaryl Drugs 0.000 claims description 23
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 23
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 23
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 22
• 125000000468 ketone group Chemical group 0.000 claims description 22
• 108091000080 Phosphotransferase Proteins 0.000 claims description 21
• 102000020233 phosphotransferase Human genes 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
• 125000005647 linker group Chemical group 0.000 claims description 19
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 18
• 125000004429 atom Chemical group 0.000 claims description 18
• 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 claims description 17
• 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 claims description 17
• 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 claims description 17
• 239000004202 carbamide Substances 0.000 claims description 17
• 101150111293 cor-1 gene Proteins 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 9
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
• 229930194542 Keto Chemical group 0.000 claims description 8
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
• 230000005764 inhibitory process Effects 0.000 claims description 8
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 8
• 125000001725 pyrenyl group Chemical group 0.000 claims description 8
• 229910052707 ruthenium Inorganic materials 0.000 claims description 8
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 8
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
• 150000002923 oximes Chemical class 0.000 claims description 7
• 239000002689 soil Substances 0.000 claims description 7
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 6
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 6
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 claims description 6
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 claims description 6
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 5
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
• GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 4
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 4
• 210000004907 gland Anatomy 0.000 claims description 4
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
• 229910052698 phosphorus Inorganic materials 0.000 claims description 4
• 150000004032 porphyrins Chemical class 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
• 230000001028 anti-proliverative effect Effects 0.000 claims description 3
• 208000035475 disorder Diseases 0.000 claims description 3
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 3
• 208000026278 immune system disease Diseases 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
• MDKHWJFKHDRFFZ-UHFFFAOYSA-N 3,5-dimethylmorpholine Chemical compound CC1COCC(C)N1 MDKHWJFKHDRFFZ-UHFFFAOYSA-N 0.000 claims description 2
• 241000239226 Scorpiones Species 0.000 claims description 2
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 210000004369 blood Anatomy 0.000 claims description 2
• 239000008280 blood Substances 0.000 claims description 2
• 229910052801 chlorine Inorganic materials 0.000 claims description 2
• 238000003776 cleavage reaction Methods 0.000 claims description 2
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
• 239000007789 gas Substances 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 235000013336 milk Nutrition 0.000 claims description 2
• 239000008267 milk Substances 0.000 claims description 2
• 210000004080 milk Anatomy 0.000 claims description 2
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
• 230000007017 scission Effects 0.000 claims description 2
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 12
• 125000001589 carboacyl group Chemical group 0.000 claims 7
• 150000003573 thiols Chemical class 0.000 claims 7
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 4
• SFWWGMKXCYLZEG-YFKPBYRVSA-N (3s)-3-methylmorpholine Chemical compound C[C@H]1COCCN1 SFWWGMKXCYLZEG-YFKPBYRVSA-N 0.000 claims 3
• 241000282412 Homo Species 0.000 claims 3
• 210000003462 vein Anatomy 0.000 claims 3
• CLAHOZSYMRNIPY-UHFFFAOYSA-N 2-hydroxyethylurea Chemical compound NC(=O)NCCO CLAHOZSYMRNIPY-UHFFFAOYSA-N 0.000 claims 2
• WIISOYLZJJYTHT-UHFFFAOYSA-N 2-methyl-1h-pyrazol-5-one Chemical compound CN1C=CC(O)=N1 WIISOYLZJJYTHT-UHFFFAOYSA-N 0.000 claims 2
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 2
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims 2
• UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 claims 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
• 125000001041 indolyl group Chemical group 0.000 claims 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 2
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
• TVCXVUHHCUYLGX-UHFFFAOYSA-N 2-Methylpyrrole Chemical compound CC1=CC=CN1 TVCXVUHHCUYLGX-UHFFFAOYSA-N 0.000 claims 1
• SNHLRJSKPOPBPO-UHFFFAOYSA-N 2-fluoroethylurea Chemical compound NC(=O)NCCF SNHLRJSKPOPBPO-UHFFFAOYSA-N 0.000 claims 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
• WGZYVHFXLPDNDL-UHFFFAOYSA-N 4-benzoyl-2-phenylpyrazole-3-carbonitrile Chemical group C=1C=CC=CC=1C(=O)C(=C1C#N)C=NN1C1=CC=CC=C1 WGZYVHFXLPDNDL-UHFFFAOYSA-N 0.000 claims 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims 1
• XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims 1
• 241000282320 Panthera leo Species 0.000 claims 1
• ZUWZHGIJTPZRAX-UHFFFAOYSA-N S.NN Chemical compound S.NN ZUWZHGIJTPZRAX-UHFFFAOYSA-N 0.000 claims 1
• 206010039424 Salivary hypersecretion Diseases 0.000 claims 1
• 241001061127 Thione Species 0.000 claims 1
• IYCUCQGVEZOMMV-UHFFFAOYSA-N aminomethanethiol Chemical compound NCS IYCUCQGVEZOMMV-UHFFFAOYSA-N 0.000 claims 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
• 239000012965 benzophenone Substances 0.000 claims 1
• 125000005997 bromomethyl group Chemical group 0.000 claims 1
• OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims 1
• 229960004126 codeine Drugs 0.000 claims 1
• CLMGCKCDSPUQEE-UHFFFAOYSA-N cyclopropylurea Chemical compound NC(=O)NC1CC1 CLMGCKCDSPUQEE-UHFFFAOYSA-N 0.000 claims 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims 1
• 239000003085 diluting agent Substances 0.000 claims 1
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
• 206010020718 hyperplasia Diseases 0.000 claims 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 claims 1
• 208000026451 salivation Diseases 0.000 claims 1
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
• 229910021653 sulphate ion Inorganic materials 0.000 claims 1
• 125000004149 thio group Chemical group *S* 0.000 claims 1
• 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 claims 1
• 150000003852 triazoles Chemical class 0.000 claims 1
• 229910052727 yttrium Inorganic materials 0.000 claims 1
• VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 abstract description 32
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 abstract description 32
• 238000002360 preparation method Methods 0.000 abstract description 8
• 230000001404 mediated effect Effects 0.000 abstract description 5
• 230000008569 process Effects 0.000 abstract description 3
• 102000038030 PI3Ks Human genes 0.000 abstract 1
• 108091007960 PI3Ks Proteins 0.000 abstract 1
• 238000002560 therapeutic procedure Methods 0.000 abstract 1
• 239000010949 copper Substances 0.000 description 153
• 239000002585 base Substances 0.000 description 121
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
• 125000003396 thiol group Chemical class [H]S* 0.000 description 37
• 235000019439 ethyl acetate Nutrition 0.000 description 29
• 102000004190 Enzymes Human genes 0.000 description 28
• 108090000790 Enzymes Proteins 0.000 description 28
• 125000002252 acyl group Chemical group 0.000 description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
• 238000005481 NMR spectroscopy Methods 0.000 description 24
• 239000000243 solution Substances 0.000 description 24
• 239000002253 acid Substances 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
• 210000004027 cell Anatomy 0.000 description 16
• 125000004122 cyclic group Chemical group 0.000 description 16
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 15
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 14
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
• 239000000463 material Substances 0.000 description 14
• 125000003226 pyrazolyl group Chemical group 0.000 description 14
• 241000894007 species Species 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 13
• 125000001153 fluoro group Chemical group F* 0.000 description 13
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 13
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