ME01934B - Derivati pirazola kao modulatori protein kinaze - Google Patents

Info

Publication number

ME01934B

ME01934B MEP-2010-532A MEP53210A ME01934B ME 01934 B ME01934 B ME 01934B ME P53210 A MEP53210 A ME P53210A ME 01934 B ME01934 B ME 01934B

Authority

ME

Montenegro

Prior art keywords

phenyl

group

pyrazol

chloro

methyl

Prior art date

2003-12-23

Links

• Espacenet
• Global Dossier
• Discuss

• 102000001253 Protein Kinase Human genes 0.000 title description 8
• 108060006633 protein kinase Proteins 0.000 title description 8
• 150000003217 pyrazoles Chemical class 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 439
• 238000000034 method Methods 0.000 claims description 193
• -1 pyrrolidinocarbonyl Chemical group 0.000 claims description 188
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 96
• 125000001424 substituent group Chemical group 0.000 claims description 88
• 108091008611 Protein Kinase B Proteins 0.000 claims description 78
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 76
• 229910052757 nitrogen Inorganic materials 0.000 claims description 70
• 125000005647 linker group Chemical group 0.000 claims description 69
• 229910052739 hydrogen Inorganic materials 0.000 claims description 67
• 239000001257 hydrogen Substances 0.000 claims description 66
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
• 229910052760 oxygen Inorganic materials 0.000 claims description 64
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
• 125000004432 carbon atom Chemical group C* 0.000 claims description 56
• 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 claims description 55
• 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 claims description 55
• 125000000623 heterocyclic group Chemical group 0.000 claims description 54
• 238000011282 treatment Methods 0.000 claims description 54
• 201000010099 disease Diseases 0.000 claims description 53
• 125000004429 atom Chemical group 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 46
• 125000001072 heteroaryl group Chemical group 0.000 claims description 45
• 125000005842 heteroatom Chemical group 0.000 claims description 45
• 239000002253 acid Substances 0.000 claims description 42
• 125000003118 aryl group Chemical group 0.000 claims description 42
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
• 206010028980 Neoplasm Diseases 0.000 claims description 41
• 238000006243 chemical reaction Methods 0.000 claims description 41
• 125000002837 carbocyclic group Chemical group 0.000 claims description 39
• 150000002431 hydrogen Chemical class 0.000 claims description 38
• 229910052731 fluorine Inorganic materials 0.000 claims description 37
• 229910052736 halogen Inorganic materials 0.000 claims description 37
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 36
• 239000011737 fluorine Substances 0.000 claims description 33
• 229910052717 sulfur Inorganic materials 0.000 claims description 31
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 30
• 125000002950 monocyclic group Chemical group 0.000 claims description 30
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 29
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 29
• 229910052801 chlorine Inorganic materials 0.000 claims description 28
• 239000000460 chlorine Substances 0.000 claims description 27
• 230000002265 prevention Effects 0.000 claims description 25
• 239000003814 drug Substances 0.000 claims description 24
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 23
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 23
• 125000004122 cyclic group Chemical group 0.000 claims description 23
• 150000002148 esters Chemical class 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 229910052794 bromium Inorganic materials 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 21
• 125000004043 oxo group Chemical group O=* 0.000 claims description 21
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
• 230000001404 mediated effect Effects 0.000 claims description 20
• 150000001204 N-oxides Chemical class 0.000 claims description 17
• 239000002585 base Substances 0.000 claims description 16
• 125000002619 bicyclic group Chemical group 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 15
• 125000004423 acyloxy group Chemical group 0.000 claims description 14
• 230000010261 cell growth Effects 0.000 claims description 14
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• 230000002159 abnormal effect Effects 0.000 claims description 13
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
• 230000006907 apoptotic process Effects 0.000 claims description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 239000012453 solvate Substances 0.000 claims description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 11
• 239000003054 catalyst Substances 0.000 claims description 11
• 239000001301 oxygen Substances 0.000 claims description 11
• 238000002360 preparation method Methods 0.000 claims description 11
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
• IVDLDHJBOWQROZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(Cl)C=C1 IVDLDHJBOWQROZ-UHFFFAOYSA-N 0.000 claims description 10
• 125000002252 acyl group Chemical group 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• 206010006187 Breast cancer Diseases 0.000 claims description 9
• 208000026310 Breast neoplasm Diseases 0.000 claims description 9
• 239000003638 chemical reducing agent Substances 0.000 claims description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 9
• 229940079593 drug Drugs 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• HWVGILTYGZFGLR-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN)C1=CC=C(Cl)C=C1 HWVGILTYGZFGLR-UHFFFAOYSA-N 0.000 claims description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 8
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
• 206010060862 Prostate cancer Diseases 0.000 claims description 7
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 7
• 125000001246 bromo group Chemical group Br* 0.000 claims description 7
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 229910052740 iodine Inorganic materials 0.000 claims description 7
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
• 230000035755 proliferation Effects 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
• 210000000481 breast Anatomy 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 206010033128 Ovarian cancer Diseases 0.000 claims description 5
• 230000004069 differentiation Effects 0.000 claims description 5
• 239000011630 iodine Chemical group 0.000 claims description 5
• 229910052763 palladium Inorganic materials 0.000 claims description 5
• 210000002307 prostate Anatomy 0.000 claims description 5
• 210000001685 thyroid gland Anatomy 0.000 claims description 5
• SSRZUATVJOAMJJ-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methyl]piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)N1CCNCC1 SSRZUATVJOAMJJ-UHFFFAOYSA-N 0.000 claims description 4
• MGYPCCQLBPTNML-UHFFFAOYSA-N 1-[(4-chlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)N1CCNCC1 MGYPCCQLBPTNML-UHFFFAOYSA-N 0.000 claims description 4
• IIRWNGPLJQXWFJ-UHFFFAOYSA-N 2-amino-1-(4-chlorophenyl)-1-[4-(1h-pyrazol-4-yl)phenyl]ethanol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(O)(CN)C1=CC=C(Cl)C=C1 IIRWNGPLJQXWFJ-UHFFFAOYSA-N 0.000 claims description 4
• PMSURQYNKZJHOA-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCN)C1=CC=C(Cl)C=C1 PMSURQYNKZJHOA-UHFFFAOYSA-N 0.000 claims description 4
• WZTPTWWAPVMONU-UHFFFAOYSA-N 4-[4-(2-methoxyethoxy)phenyl]-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=CC(OCCOC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 WZTPTWWAPVMONU-UHFFFAOYSA-N 0.000 claims description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 230000003325 follicular Effects 0.000 claims description 4
• 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 238000006268 reductive amination reaction Methods 0.000 claims description 4
• 229930192474 thiophene Natural products 0.000 claims description 4
• BSDJRCSCDXPNOO-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]ethanol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(O)(CNC)C1=CC=C(Cl)C=C1 BSDJRCSCDXPNOO-UHFFFAOYSA-N 0.000 claims description 3
• KAPLTLJNVKHMLV-UHFFFAOYSA-N 2-(4-chlorophenyl)-n,n-dimethyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN(C)C)C1=CC=C(Cl)C=C1 KAPLTLJNVKHMLV-UHFFFAOYSA-N 0.000 claims description 3
• GCIJUVFCSAIPKY-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CCN)C(C=C1)=CC=C1C=1C=NNC=1 GCIJUVFCSAIPKY-UHFFFAOYSA-N 0.000 claims description 3
• MLWHKTLBRHPGGV-UHFFFAOYSA-N 3-(4-chlorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)C1=CC=C(Cl)C=C1 MLWHKTLBRHPGGV-UHFFFAOYSA-N 0.000 claims description 3
• SAJGJQMGFRPHDO-UHFFFAOYSA-N 3-(4-phenoxyphenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCN)C(C=C1)=CC=C1OC1=CC=CC=C1 SAJGJQMGFRPHDO-UHFFFAOYSA-N 0.000 claims description 3
• GNOJHSRNZXLFFX-UHFFFAOYSA-N 3-phenyl-2-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN)CC1=CC=CC=C1 GNOJHSRNZXLFFX-UHFFFAOYSA-N 0.000 claims description 3
• LQLAOBTZZLDUJD-UHFFFAOYSA-N 4-(3-chloro-4-methoxyphenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=C(Cl)C(OC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 LQLAOBTZZLDUJD-UHFFFAOYSA-N 0.000 claims description 3
• LZMOSYUFVYJEPY-UHFFFAOYSA-N AT7867 Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 LZMOSYUFVYJEPY-UHFFFAOYSA-N 0.000 claims description 3
• 206010009944 Colon cancer Diseases 0.000 claims description 3
• 125000004442 acylamino group Chemical group 0.000 claims description 3
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 3
• AVMYSWGHPQZPKK-UHFFFAOYSA-N n-methyl-2-(4-pyrazin-2-yloxyphenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C(C=C1)=CC=C1OC1=CN=CC=N1 AVMYSWGHPQZPKK-UHFFFAOYSA-N 0.000 claims description 3
• 210000002784 stomach Anatomy 0.000 claims description 3
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
• YPAHULZLTKIWQR-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1C=NC=C1 YPAHULZLTKIWQR-UHFFFAOYSA-N 0.000 claims description 2
• HLVUQRHDBODCFJ-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCNCC1 HLVUQRHDBODCFJ-UHFFFAOYSA-N 0.000 claims description 2
• XGMBCVUAPHUSMA-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCCCC1 XGMBCVUAPHUSMA-UHFFFAOYSA-N 0.000 claims description 2
• FVHKVHULVJSUGS-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propyl]imidazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CCN1C=NC=C1 FVHKVHULVJSUGS-UHFFFAOYSA-N 0.000 claims description 2
• YMOIUHMRAZGIKG-UHFFFAOYSA-N 1-[3-phenoxy-3-[4-(1h-pyrazol-4-yl)phenyl]propyl]imidazole Chemical compound C=1C=CC=CC=1OC(C=1C=CC(=CC=1)C1=CNN=C1)CCN1C=CN=C1 YMOIUHMRAZGIKG-UHFFFAOYSA-N 0.000 claims description 2
• YHDRFTQLBPOIDN-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CN)C(C=C1)=CC=C1C=1C=NNC=1 YHDRFTQLBPOIDN-UHFFFAOYSA-N 0.000 claims description 2
• KTCZKWVYZSCJKV-UHFFFAOYSA-N 2-(3-chloro-4-methoxyphenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C1=C(Cl)C(OC)=CC=C1C(CN)C1=CC=C(C2=CNN=C2)C=C1 KTCZKWVYZSCJKV-UHFFFAOYSA-N 0.000 claims description 2
• YVVUEDSXVDPICU-UHFFFAOYSA-N 2-(3-chloro-4-methoxyphenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(OC)C(Cl)=CC=1C(CNC)C(C=C1)=CC=C1C=1C=NNC=1 YVVUEDSXVDPICU-UHFFFAOYSA-N 0.000 claims description 2
• JQAPAUAVUKTZPG-UHFFFAOYSA-N 2-(3-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=CC(Cl)=CC=1C(CNC)C(C=C1)=CC=C1C=1C=NNC=1 JQAPAUAVUKTZPG-UHFFFAOYSA-N 0.000 claims description 2
• FSSABRHCBJFDJH-UHFFFAOYSA-N 2-(4-chloro-3-fluorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(Cl)C(F)=CC=1C(CN)C(C=C1)=CC=C1C=1C=NNC=1 FSSABRHCBJFDJH-UHFFFAOYSA-N 0.000 claims description 2
• OQPBTDKODFFOER-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]morpholine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)OCCNC1 OQPBTDKODFFOER-UHFFFAOYSA-N 0.000 claims description 2
• WJIBOVOTOYHIAY-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-fluoro-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(F)(CN)C1=CC=C(Cl)C=C1 WJIBOVOTOYHIAY-UHFFFAOYSA-N 0.000 claims description 2
• HGJXGKHMXZTCMI-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(cyclopropylmethyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CNCC1CC1 HGJXGKHMXZTCMI-UHFFFAOYSA-N 0.000 claims description 2
• HBXOAWAFHYIFMJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-ethyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNCC)C1=CC=C(Cl)C=C1 HBXOAWAFHYIFMJ-UHFFFAOYSA-N 0.000 claims description 2
• UAALBJPKYVOYRB-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]acetamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C(=O)NC)C1=CC=C(Cl)C=C1 UAALBJPKYVOYRB-UHFFFAOYSA-N 0.000 claims description 2
• YMBOWJASIPJHPL-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C)(CNC)C1=CC=C(Cl)C=C1 YMBOWJASIPJHPL-UHFFFAOYSA-N 0.000 claims description 2
• RQEUDJXTUCAVAA-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(F)C=C1 RQEUDJXTUCAVAA-UHFFFAOYSA-N 0.000 claims description 2
• HNVSGFVICJTHBH-UHFFFAOYSA-N 2-(4-methoxyphenyl)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C1=CC=C(OC)C=C1 HNVSGFVICJTHBH-UHFFFAOYSA-N 0.000 claims description 2
• XNIAUSRAGOBQDX-UHFFFAOYSA-N 2-[(4-chlorophenyl)-[4-(1h-pyrazol-4-yl)phenyl]methoxy]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(OCCN)C1=CC=C(Cl)C=C1 XNIAUSRAGOBQDX-UHFFFAOYSA-N 0.000 claims description 2
• NQEBEJVATHZQHM-UHFFFAOYSA-N 2-[3-(3,5-dimethyl-1h-pyrazol-4-yl)phenyl]-1-phenylethanamine Chemical compound CC1=NNC(C)=C1C1=CC=CC(CC(N)C=2C=CC=CC=2)=C1 NQEBEJVATHZQHM-UHFFFAOYSA-N 0.000 claims description 2
• QBUGJWXOVSASPH-UHFFFAOYSA-N 2-[4-(3,5-dimethyl-1h-pyrazol-4-yl)phenyl]-2-phenylethanamine Chemical compound CC1=NNC(C)=C1C1=CC=C(C(CN)C=2C=CC=CC=2)C=C1 QBUGJWXOVSASPH-UHFFFAOYSA-N 0.000 claims description 2
• PEVARZMNCRMKAQ-UHFFFAOYSA-N 2-[4-[2-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]ethyl]phenoxy]pyridine-4-carboxamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C(C=C1)=CC=C1OC1=CC(C(N)=O)=CC=N1 PEVARZMNCRMKAQ-UHFFFAOYSA-N 0.000 claims description 2
• HBYQXDUYJRDECS-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]amino]ethanol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNCCO)C1=CC=C(Cl)C=C1 HBYQXDUYJRDECS-UHFFFAOYSA-N 0.000 claims description 2
• MWSMBSLUKDQMPK-UHFFFAOYSA-N 2-phenyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN)C1=CC=CC=C1 MWSMBSLUKDQMPK-UHFFFAOYSA-N 0.000 claims description 2
• WBUYUGCRHOCOID-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CC(=O)N)C(C=C1)=CC=C1C=1C=NNC=1 WBUYUGCRHOCOID-UHFFFAOYSA-N 0.000 claims description 2
• CSPQEGYWLIIPIZ-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-[6-(1h-pyrazol-4-yl)pyridin-3-yl]propan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(CCN)C(C=N1)=CC=C1C=1C=NNC=1 CSPQEGYWLIIPIZ-UHFFFAOYSA-N 0.000 claims description 2
• MSRWMOWZENJWHN-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(F)C(F)=CC=1C(CCNC)C(C=C1)=CC=C1C=1C=NNC=1 MSRWMOWZENJWHN-UHFFFAOYSA-N 0.000 claims description 2
• FGCYAZQVNZXMNP-UHFFFAOYSA-N 3-(3-chloro-4-methoxyphenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C1=C(Cl)C(OC)=CC=C1C(CCN)C1=CC=C(C2=CNN=C2)C=C1 FGCYAZQVNZXMNP-UHFFFAOYSA-N 0.000 claims description 2
• PRHHLNJGKNRDQE-UHFFFAOYSA-N 3-(3-chloro-4-methoxyphenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(OC)C(Cl)=CC=1C(CCNC)C(C=C1)=CC=C1C=1C=NNC=1 PRHHLNJGKNRDQE-UHFFFAOYSA-N 0.000 claims description 2
• XTCPRZFKMFVDJF-UHFFFAOYSA-N 3-(3-chlorophenoxy)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)OC1=CC=CC(Cl)=C1 XTCPRZFKMFVDJF-UHFFFAOYSA-N 0.000 claims description 2
• HEDXUHRIYXUKSI-UHFFFAOYSA-N 3-(3-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=CC(Cl)=CC=1C(CCN)C(C=C1)=CC=C1C=1C=NNC=1 HEDXUHRIYXUKSI-UHFFFAOYSA-N 0.000 claims description 2
• BLVZFJHSAUCMFX-UHFFFAOYSA-N 3-(3-chlorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=CC(Cl)=CC=1C(CCNC)C(C=C1)=CC=C1C=1C=NNC=1 BLVZFJHSAUCMFX-UHFFFAOYSA-N 0.000 claims description 2
• NZKIKXUXRVDQAK-UHFFFAOYSA-N 3-(4-chlorophenyl)-3-[4-(1h-pyrazol-4-yl)phenyl]propanamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CC(=O)N)C1=CC=C(Cl)C=C1 NZKIKXUXRVDQAK-UHFFFAOYSA-N 0.000 claims description 2
• PMQWUCJKVOBNEE-UHFFFAOYSA-N 3-(4-fluorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)C1=CC=C(F)C=C1 PMQWUCJKVOBNEE-UHFFFAOYSA-N 0.000 claims description 2
• VRICFPVOFWNRLE-UHFFFAOYSA-N 3-phenyl-2-[3-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=CC(C2=CNN=C2)=CC=1C(CN)CC1=CC=CC=C1 VRICFPVOFWNRLE-UHFFFAOYSA-N 0.000 claims description 2
• ZJEQGMQJPQNZJK-UHFFFAOYSA-N 3-phenyl-2-[3-(1h-pyrazol-4-yl)phenyl]propanenitrile Chemical compound C=1C=CC(C2=CNN=C2)=CC=1C(C#N)CC1=CC=CC=C1 ZJEQGMQJPQNZJK-UHFFFAOYSA-N 0.000 claims description 2
• USUVTKQVEFVSHN-UHFFFAOYSA-N 4-(2-chloro-3-fluorophenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound FC1=CC=CC(C2(CCNCC2)C=2C=CC(=CC=2)C2=CNN=C2)=C1Cl USUVTKQVEFVSHN-UHFFFAOYSA-N 0.000 claims description 2
• MHPPVGSDNKCZMG-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 MHPPVGSDNKCZMG-UHFFFAOYSA-N 0.000 claims description 2
• YLEMKLICYJNLDA-UHFFFAOYSA-N 4-(4-chloro-3-fluorophenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=C(Cl)C(F)=CC(C2(CCNCC2)C=2C=CC(=CC=2)C2=CNN=C2)=C1 YLEMKLICYJNLDA-UHFFFAOYSA-N 0.000 claims description 2
• JBBMHGJGPVSWOO-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-methyl-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1CN(C)CCC1(C=1C=CC(=CC=1)C1=CNN=C1)C1=CC=C(Cl)C=C1 JBBMHGJGPVSWOO-UHFFFAOYSA-N 0.000 claims description 2
• PYVKMDJDKCKVJO-UHFFFAOYSA-N 4-(4-methoxyphenyl)-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=CC(OC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 PYVKMDJDKCKVJO-UHFFFAOYSA-N 0.000 claims description 2
• HGHCXFKOUIZYGF-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]morpholine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCOCC1 HGHCXFKOUIZYGF-UHFFFAOYSA-N 0.000 claims description 2
• PAJNBJLDVKJXNX-UHFFFAOYSA-N 4-[3-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]propyl]phenol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)C1=CC=C(O)C=C1 PAJNBJLDVKJXNX-UHFFFAOYSA-N 0.000 claims description 2
• IQTMZQRPCUSIKL-UHFFFAOYSA-N 4-[4-(3,5-dimethyl-1h-pyrazol-4-yl)phenyl]-4-phenylpiperidine Chemical compound CC1=NNC(C)=C1C1=CC=C(C2(CCNCC2)C=2C=CC=CC=2)C=C1 IQTMZQRPCUSIKL-UHFFFAOYSA-N 0.000 claims description 2
• JJMWTFLOALEUFK-UHFFFAOYSA-N 4-[4-[1-(4-chlorophenyl)-3-pyrrolidin-1-ylpropyl]phenyl]-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CCN1CCCC1 JJMWTFLOALEUFK-UHFFFAOYSA-N 0.000 claims description 2
• LMQVASLLHRUDEK-UHFFFAOYSA-N 4-[4-[2-(azetidin-1-yl)-1-(4-chlorophenoxy)ethyl]phenyl]-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1OC(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCC1 LMQVASLLHRUDEK-UHFFFAOYSA-N 0.000 claims description 2
• GXIKHGUANWIUPY-UHFFFAOYSA-N 4-[4-[2-(azetidin-1-yl)-1-(4-chlorophenyl)ethyl]phenyl]-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCC1 GXIKHGUANWIUPY-UHFFFAOYSA-N 0.000 claims description 2
• PEEKZDAJUZOSLT-UHFFFAOYSA-N 4-[4-[3-(azetidin-1-yl)-1-(4-chlorophenyl)propyl]phenyl]-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CCN1CCC1 PEEKZDAJUZOSLT-UHFFFAOYSA-N 0.000 claims description 2
• PBNKBTUXTSOMLR-UHFFFAOYSA-N 4-[4-[4-(1h-pyrazol-4-yl)phenyl]piperidin-4-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 PBNKBTUXTSOMLR-UHFFFAOYSA-N 0.000 claims description 2
• LKFDJWGYWDCRPC-UHFFFAOYSA-N 4-phenyl-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1CNCCC1(C=1C=CC(=CC=1)C1=CNN=C1)C1=CC=CC=C1 LKFDJWGYWDCRPC-UHFFFAOYSA-N 0.000 claims description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
• 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 claims description 2
• 201000010208 Seminoma Diseases 0.000 claims description 2
• 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 claims description 2
• 201000006083 Xeroderma Pigmentosum Diseases 0.000 claims description 2
• 210000003679 cervix uteri Anatomy 0.000 claims description 2
• 210000001072 colon Anatomy 0.000 claims description 2
• 125000004188 dichlorophenyl group Chemical group 0.000 claims description 2
• 210000004696 endometrium Anatomy 0.000 claims description 2
• 201000004101 esophageal cancer Diseases 0.000 claims description 2
• 208000007276 esophageal squamous cell carcinoma Diseases 0.000 claims description 2
• 210000003238 esophagus Anatomy 0.000 claims description 2
• 210000000232 gallbladder Anatomy 0.000 claims description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
• 210000003734 kidney Anatomy 0.000 claims description 2
• 210000004185 liver Anatomy 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• RUGFXXKVNXNFGY-UHFFFAOYSA-N n,n-dimethyl-2,2-bis[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN(C)C)C(C=C1)=CC=C1C=1C=NNC=1 RUGFXXKVNXNFGY-UHFFFAOYSA-N 0.000 claims description 2
• RLUISSQWDGXBRY-UHFFFAOYSA-N n-[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]propan-2-amine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC(C)C)C1=CC=C(Cl)C=C1 RLUISSQWDGXBRY-UHFFFAOYSA-N 0.000 claims description 2
• IGGFWLLVYRWCCO-UHFFFAOYSA-N n-methyl-2,2-bis[4-(1h-pyrazol-4-yl)phenyl]acetamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C(=O)NC)C(C=C1)=CC=C1C=1C=NNC=1 IGGFWLLVYRWCCO-UHFFFAOYSA-N 0.000 claims description 2
• GDKGYPHOFSWULD-UHFFFAOYSA-N n-methyl-2-(4-phenoxyphenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)C(C=C1)=CC=C1OC1=CC=CC=C1 GDKGYPHOFSWULD-UHFFFAOYSA-N 0.000 claims description 2
• DKDQKBGMSVFFGE-UHFFFAOYSA-N n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]-2-(4-pyridin-3-ylphenyl)ethanamine Chemical compound C=1C=C(C=2C=NC=CC=2)C=CC=1C(CNC)C(C=C1)=CC=C1C=1C=NNC=1 DKDQKBGMSVFFGE-UHFFFAOYSA-N 0.000 claims description 2
• WRTRCQJKGMMJCS-UHFFFAOYSA-N n-methyl-2-phenoxy-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)OC1=CC=CC=C1 WRTRCQJKGMMJCS-UHFFFAOYSA-N 0.000 claims description 2
• PGDUARZFLYYKNP-UHFFFAOYSA-N n-methyl-2-phenyl-2-[6-(1h-pyrazol-4-yl)pyridin-3-yl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)N=CC=1C(CNC)C1=CC=CC=C1 PGDUARZFLYYKNP-UHFFFAOYSA-N 0.000 claims description 2
• GSCXAIQOLGKSEW-UHFFFAOYSA-N n-methyl-3-naphthalen-2-yl-3-[4-(1h-pyrazol-4-yl)phenyl]propan-1-amine Chemical compound C=1C=C2C=CC=CC2=CC=1C(CCNC)C(C=C1)=CC=C1C=1C=NNC=1 GSCXAIQOLGKSEW-UHFFFAOYSA-N 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• 201000008968 osteosarcoma Diseases 0.000 claims description 2
• 210000001672 ovary Anatomy 0.000 claims description 2
• 210000000496 pancreas Anatomy 0.000 claims description 2
• 210000003491 skin Anatomy 0.000 claims description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 2
• 208000001608 teratocarcinoma Diseases 0.000 claims description 2
• 125000001544 thienyl group Chemical group 0.000 claims description 2
• 210000003932 urinary bladder Anatomy 0.000 claims description 2
• 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 claims 2
• PVGMKLLGQDLGRJ-UHFFFAOYSA-N 1-methyl-4-[phenyl-[4-(1h-pyrazol-4-yl)phenyl]methyl]-1,4-diazepane Chemical compound C1CN(C)CCCN1C(C=1C=CC(=CC=1)C1=CNN=C1)C1=CC=CC=C1 PVGMKLLGQDLGRJ-UHFFFAOYSA-N 0.000 claims 1
• VTNKIRBLRDIXRQ-UHFFFAOYSA-N 2-(methylamino)-1-(4-nitrophenyl)-1-[4-(1h-pyrazol-4-yl)phenyl]ethanol Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(O)(CNC)C(C=C1)=CC=C1C=1C=NNC=1 VTNKIRBLRDIXRQ-UHFFFAOYSA-N 0.000 claims 1
• AOJCEFPPEOPJAD-UHFFFAOYSA-N 4-[4-[4-(1h-pyrazol-4-yl)phenyl]piperidin-4-yl]phenol Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 AOJCEFPPEOPJAD-UHFFFAOYSA-N 0.000 claims 1
• HQMWZYTXIFWKPY-UHFFFAOYSA-N 4-[4-[4-(4-chlorophenyl)piperidin-4-yl]phenyl]-1h-pyrazole-5-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(=CC=2)C=2C(=NNC=2)C#N)CCNCC1 HQMWZYTXIFWKPY-UHFFFAOYSA-N 0.000 claims 1
• 201000009030 Carcinoma Diseases 0.000 claims 1
• 206010023347 Keratoacanthoma Diseases 0.000 claims 1
• KMBPALGRPXPTJC-UHFFFAOYSA-N n,n-dimethyl-3-[4-(1h-pyrazol-4-yl)phenyl]-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C(C=C1)=CC=C1C=1C=NNC=1 KMBPALGRPXPTJC-UHFFFAOYSA-N 0.000 claims 1
• 210000000653 nervous system Anatomy 0.000 claims 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 141
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 92
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 78
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
• 239000000243 solution Substances 0.000 description 59
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 239000000203 mixture Substances 0.000 description 49
• 150000001412 amines Chemical class 0.000 description 45
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
• 239000002904 solvent Substances 0.000 description 42
• 230000002829 reductive effect Effects 0.000 description 41
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
• 238000005481 NMR spectroscopy Methods 0.000 description 40
• 238000005160 1H NMR spectroscopy Methods 0.000 description 37
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 36
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
• 239000011541 reaction mixture Substances 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
• 239000003480 eluent Substances 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
• 230000000694 effects Effects 0.000 description 30
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
• 239000000047 product Substances 0.000 description 28
• 150000001721 carbon Chemical group 0.000 description 26
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
• 235000019341 magnesium sulphate Nutrition 0.000 description 26
• 239000003112 inhibitor Substances 0.000 description 24
• 238000004440 column chromatography Methods 0.000 description 23
• 239000000543 intermediate Substances 0.000 description 23
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 22
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 21
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 21
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 20
• 238000006069 Suzuki reaction reaction Methods 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• 239000003208 petroleum Substances 0.000 description 20
• 125000000217 alkyl group Chemical group 0.000 description 19
• 150000001408 amides Chemical class 0.000 description 19
• 239000007858 starting material Substances 0.000 description 19
• 229910021529 ammonia Inorganic materials 0.000 description 18
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 18
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 18
• TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 17
• 239000012043 crude product Substances 0.000 description 17
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 16
• 108090000623 proteins and genes Proteins 0.000 description 16
• 125000003277 amino group Chemical group 0.000 description 15
• 229910052681 coesite Inorganic materials 0.000 description 15
• 239000007788 liquid Substances 0.000 description 15
• 229910052682 stishovite Inorganic materials 0.000 description 15
• 229910052905 tridymite Inorganic materials 0.000 description 15
• 108091000080 Phosphotransferase Proteins 0.000 description 14
• 229910052906 cristobalite Inorganic materials 0.000 description 14
• 235000019253 formic acid Nutrition 0.000 description 14
• 102000020233 phosphotransferase Human genes 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 13
• CDEMHJCJMMOFMB-UHFFFAOYSA-M ClC1=CC=C([Mg]Br)C=C1 Chemical compound ClC1=CC=C([Mg]Br)C=C1 CDEMHJCJMMOFMB-UHFFFAOYSA-M 0.000 description 13
• 238000010438 heat treatment Methods 0.000 description 13
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 13
• 230000002401 inhibitory effect Effects 0.000 description 13
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 13
• 239000000377 silicon dioxide Substances 0.000 description 13
• 230000004083 survival effect Effects 0.000 description 13
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
• 230000035772 mutation Effects 0.000 description 12
• 150000002924 oxiranes Chemical class 0.000 description 12
• 125000006239 protecting group Chemical group 0.000 description 12
• 235000012239 silicon dioxide Nutrition 0.000 description 12
• 239000011780 sodium chloride Substances 0.000 description 12
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 150000001299 aldehydes Chemical class 0.000 description 11
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
• 150000002825 nitriles Chemical class 0.000 description 11
• 230000026731 phosphorylation Effects 0.000 description 11
• 238000006366 phosphorylation reaction Methods 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 10
• 108090000790 Enzymes Proteins 0.000 description 10
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 10
• 125000005843 halogen group Chemical group 0.000 description 10
• 239000012280 lithium aluminium hydride Substances 0.000 description 10
• 230000003287 optical effect Effects 0.000 description 10
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 230000004913 activation Effects 0.000 description 9
• 238000005859 coupling reaction Methods 0.000 description 9
• 125000000753 cycloalkyl group Chemical group 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 230000037361 pathway Effects 0.000 description 9
• 102000004169 proteins and genes Human genes 0.000 description 9
• 230000001105 regulatory effect Effects 0.000 description 9
• 150000003333 secondary alcohols Chemical class 0.000 description 9
• 230000019491 signal transduction Effects 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• KYGYPNIZCSHFEW-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-phenylethanamine;hydron;chloride Chemical compound Cl.C=1C=C(Cl)C=CC=1C(CN)C1=CC=CC=C1 KYGYPNIZCSHFEW-UHFFFAOYSA-N 0.000 description 8
• 241000124008 Mammalia Species 0.000 description 8
• 108091007960 PI3Ks Proteins 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 8
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 8
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 230000012010 growth Effects 0.000 description 8
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 8
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 8
• 150000007523 nucleic acids Chemical class 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 239000007818 Grignard reagent Substances 0.000 description 7
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• 210000001744 T-lymphocyte Anatomy 0.000 description 7
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 239000011248 coating agent Substances 0.000 description 7
• 238000000576 coating method Methods 0.000 description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• 150000004795 grignard reagents Chemical class 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000002798 polar solvent Substances 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• 239000000523 sample Substances 0.000 description 7
• 238000012216 screening Methods 0.000 description 7
• 238000010561 standard procedure Methods 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• 239000003643 water by type Substances 0.000 description 7
• OUHLMDHGCXLZMY-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-chlorophenyl)propanoic acid Chemical compound C=1C=C(Br)C=CC=1C(CC(=O)O)C1=CC=C(Cl)C=C1 OUHLMDHGCXLZMY-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 6
• 238000003747 Grignard reaction Methods 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 6
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 230000002378 acidificating effect Effects 0.000 description 6
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 230000008878 coupling Effects 0.000 description 6
• 238000010168 coupling process Methods 0.000 description 6
• 150000002081 enamines Chemical class 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• 125000000524 functional group Chemical group 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 208000026278 immune system disease Diseases 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• 108020004707 nucleic acids Proteins 0.000 description 6
• 102000039446 nucleic acids Human genes 0.000 description 6
• 125000004430 oxygen atom Chemical group O* 0.000 description 6
• XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 150000005599 propionic acid derivatives Chemical class 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 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 6
• PYBKDRNCZGEHQJ-UHFFFAOYSA-N 2-(4-bromophenyl)-2-(4-chlorophenyl)-n-methylethanamine Chemical group C=1C=C(Br)C=CC=1C(CNC)C1=CC=C(Cl)C=C1 PYBKDRNCZGEHQJ-UHFFFAOYSA-N 0.000 description 5
• 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 5
• IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 5
• 239000000427 antigen Substances 0.000 description 5
• 108091007433 antigens Proteins 0.000 description 5
• 102000036639 antigens Human genes 0.000 description 5
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 125000002843 carboxylic acid group Chemical group 0.000 description 5
• 230000030833 cell death Effects 0.000 description 5
• 230000033077 cellular process Effects 0.000 description 5
• 229940095074 cyclic amp Drugs 0.000 description 5
• 238000010511 deprotection reaction Methods 0.000 description 5
• 238000003745 diagnosis Methods 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 239000000945 filler Substances 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 238000005755 formation reaction Methods 0.000 description 5
• 150000004678 hydrides Chemical class 0.000 description 5
• 230000028993 immune response Effects 0.000 description 5
• 238000007901 in situ hybridization Methods 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 150000002576 ketones Chemical class 0.000 description 5
• 230000007246 mechanism Effects 0.000 description 5
• 108020004999 messenger RNA Proteins 0.000 description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
• 230000002018 overexpression Effects 0.000 description 5
• 235000011181 potassium carbonates Nutrition 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• QVDKHOVJPVFDOG-UHFFFAOYSA-N 2-(4-bromophenyl)-2-(4-methoxyphenyl)-n-methylethanamine Chemical compound C=1C=C(OC)C=CC=1C(CNC)C1=CC=C(Br)C=C1 QVDKHOVJPVFDOG-UHFFFAOYSA-N 0.000 description 4
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 4
• SCHLKIFDLYYRIE-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-chlorophenyl)-n-methylpropanamide Chemical compound C=1C=C(Br)C=CC=1C(CC(=O)NC)C1=CC=C(Cl)C=C1 SCHLKIFDLYYRIE-UHFFFAOYSA-N 0.000 description 4
• 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 4
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
• 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 4
• 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 238000010240 RT-PCR analysis Methods 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 4
• 230000005856 abnormality Effects 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 150000008360 acrylonitriles Chemical class 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 125000006242 amine protecting group Chemical group 0.000 description 4
• 235000011114 ammonium hydroxide Nutrition 0.000 description 4
• 230000001363 autoimmune Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
• YIOCIFXUGBYCJR-UHFFFAOYSA-N bis(4-chlorophenyl)acetic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)C1=CC=C(Cl)C=C1 YIOCIFXUGBYCJR-UHFFFAOYSA-N 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 238000002648 combination therapy Methods 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 230000004064 dysfunction Effects 0.000 description 4
• 210000001035 gastrointestinal tract Anatomy 0.000 description 4
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 4
• 238000009396 hybridization Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 210000004698 lymphocyte Anatomy 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• 230000002611 ovarian Effects 0.000 description 4
• MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000003586 protic polar solvent Substances 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 238000006722 reduction reaction Methods 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 239000012279 sodium borohydride Substances 0.000 description 4
• 229910000033 sodium borohydride Inorganic materials 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 239000011593 sulfur Substances 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• 230000003827 upregulation Effects 0.000 description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 3
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
• ZVIDYKRNLNAXFT-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)ethanol Chemical compound C=1C=C(Cl)C=CC=1C(CO)C1=CC=C(Cl)C=C1 ZVIDYKRNLNAXFT-UHFFFAOYSA-N 0.000 description 3
• UUZYFBXKWIQKTF-UHFFFAOYSA-N 2-(3-bromophenyl)acetonitrile Chemical compound BrC1=CC=CC(CC#N)=C1 UUZYFBXKWIQKTF-UHFFFAOYSA-N 0.000 description 3
• GNUDAJTUCJEBEI-UHFFFAOYSA-N 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound CC1=NNC(C)=C1B1OC(C)(C)C(C)(C)O1 GNUDAJTUCJEBEI-UHFFFAOYSA-N 0.000 description 3
• UISZWYORHKBZTP-UHFFFAOYSA-N 7-methoxy-n,n-dimethyl-1h-indazole-3-carboxamide Chemical compound COC1=CC=CC2=C1NN=C2C(=O)N(C)C UISZWYORHKBZTP-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
• 108091006027 G proteins Proteins 0.000 description 3
• 102000030782 GTP binding Human genes 0.000 description 3
• 108091000058 GTP-Binding Proteins 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 206010018364 Glomerulonephritis Diseases 0.000 description 3
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 208000008589 Obesity Diseases 0.000 description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
• 101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 3
• 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 3
• 101710156940 RAC-beta serine/threonine-protein kinase Proteins 0.000 description 3
• 102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 3
• 101710103995 RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 208000005718 Stomach Neoplasms Diseases 0.000 description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 125000005907 alkyl ester group Chemical group 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 208000026935 allergic disease Diseases 0.000 description 3
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 239000003125 aqueous solvent Substances 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 3
• 230000027455 binding Effects 0.000 description 3
• 239000012472 biological sample Substances 0.000 description 3
• 125000005621 boronate group Chemical class 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 208000016097 disease of metabolism Diseases 0.000 description 3
• 125000004185 ester group Chemical group 0.000 description 3
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
• 230000002496 gastric effect Effects 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
• 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 230000004153 glucose metabolism Effects 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 210000002865 immune cell Anatomy 0.000 description 3
• 230000000415 inactivating effect Effects 0.000 description 3
• 230000002779 inactivation Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 230000002452 interceptive effect Effects 0.000 description 3
• BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 3
• 239000003550 marker Substances 0.000 description 3
• 208000030159 metabolic disease Diseases 0.000 description 3
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 125000006574 non-aromatic ring group Chemical group 0.000 description 3
• 235000020824 obesity Nutrition 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 3
• 230000001686 pro-survival effect Effects 0.000 description 3
• 230000002035 prolonged effect Effects 0.000 description 3
• 229940080818 propionamide Drugs 0.000 description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 3
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 230000008707 rearrangement Effects 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 238000007142 ring opening reaction Methods 0.000 description 3
• 239000012047 saturated solution Substances 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• 150000003431 steroids Chemical class 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 229940124530 sulfonamide Drugs 0.000 description 3
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 3
• 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 3
• VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 3
• LJKBUKUTDSVGIX-UHFFFAOYSA-N (4-bromophenyl)-(4-chlorophenyl)methanol Chemical compound C=1C=C(Br)C=CC=1C(O)C1=CC=C(Cl)C=C1 LJKBUKUTDSVGIX-UHFFFAOYSA-N 0.000 description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
• QGGFPJXPRUNQJX-UHFFFAOYSA-N 1-(4-bromophenyl)-2-(methylamino)ethanol Chemical compound CNCC(O)C1=CC=C(Br)C=C1 QGGFPJXPRUNQJX-UHFFFAOYSA-N 0.000 description 2
• PIJOWNYIEJSLJS-UHFFFAOYSA-N 1-(4-bromophenyl)-3-imidazol-1-ylpropan-1-ol Chemical compound C=1C=C(Br)C=CC=1C(O)CCN1C=CN=C1 PIJOWNYIEJSLJS-UHFFFAOYSA-N 0.000 description 2
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• ZMHWRGRAUCWINC-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)-n-methylpropanamide Chemical compound C=1C=C(Cl)C=CC=1C(C)(C(=O)NC)C1=CC=C(Cl)C=C1 ZMHWRGRAUCWINC-UHFFFAOYSA-N 0.000 description 2
• PLAJRWVPXJKVML-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)acetaldehyde Chemical compound C1=CC(Cl)=CC=C1C(C=O)C1=CC=C(Cl)C=C1 PLAJRWVPXJKVML-UHFFFAOYSA-N 0.000 description 2
• WXIUIUMOKHXLTE-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)propanoic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(O)=O)(C)C1=CC=C(Cl)C=C1 WXIUIUMOKHXLTE-UHFFFAOYSA-N 0.000 description 2
• OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 2
• JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 2
• KBDGYEUBGBWOMC-UHFFFAOYSA-N 2-(3-bromophenyl)-3-phenylpropanenitrile Chemical compound BrC1=CC=CC(C(CC=2C=CC=CC=2)C#N)=C1 KBDGYEUBGBWOMC-UHFFFAOYSA-N 0.000 description 2
• WXMLRJXLEVSVPI-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(4-iodophenyl)oxirane Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(I)=CC=2)OC1 WXMLRJXLEVSVPI-UHFFFAOYSA-N 0.000 description 2
• PNKKPFLBOWGVSF-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-phenylethanamine Chemical compound C=1C=C(Cl)C=CC=1C(CN)C1=CC=CC=C1 PNKKPFLBOWGVSF-UHFFFAOYSA-N 0.000 description 2
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
• QEHHLNLZIYNHFD-UHFFFAOYSA-N 2-[4-[4-[4-(1h-pyrazol-4-yl)phenyl]piperidin-4-yl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 QEHHLNLZIYNHFD-UHFFFAOYSA-N 0.000 description 2
• UYWMXDZBPJKBIK-UHFFFAOYSA-N 2-[4-[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]phenyl]-3-phenylpropanenitrile Chemical compound N1N=C(C(F)(F)F)C(C=2C=CC(=CC=2)C(CC=2C=CC=CC=2)C#N)=C1C UYWMXDZBPJKBIK-UHFFFAOYSA-N 0.000 description 2
• GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 2
• PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical compound [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• KWGDZXNLACICEA-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(3,4-difluorophenyl)-n-methylpropanamide Chemical compound C=1C=C(F)C(F)=CC=1C(CC(=O)NC)C1=CC=C(Br)C=C1 KWGDZXNLACICEA-UHFFFAOYSA-N 0.000 description 2
• WCBDVJFDALPLOA-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-chlorophenyl)propan-1-amine Chemical compound C=1C=C(Br)C=CC=1C(CCN)C1=CC=C(Cl)C=C1 WCBDVJFDALPLOA-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 2
• CWAWARVOQVUECX-UHFFFAOYSA-N 4-(4-bromophenyl)-4-(4-chlorophenyl)-1-methylpiperidine Chemical compound C1CN(C)CCC1(C=1C=CC(Br)=CC=1)C1=CC=C(Cl)C=C1 CWAWARVOQVUECX-UHFFFAOYSA-N 0.000 description 2
• HMEHLWUVHGJFIM-UHFFFAOYSA-N 4-(4-bromophenyl)-4-(4-chlorophenyl)piperidine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(Br)=CC=2)CCNCC1 HMEHLWUVHGJFIM-UHFFFAOYSA-N 0.000 description 2
• YHAHQHWOMTWBPW-UHFFFAOYSA-N 4-(4-bromophenyl)-5-methyl-1h-pyrazole Chemical compound CC1=NNC=C1C1=CC=C(Br)C=C1 YHAHQHWOMTWBPW-UHFFFAOYSA-N 0.000 description 2
• UPPCPNIWSRMOQZ-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-phenylpiperidine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC=CC=2)CCNCC1 UPPCPNIWSRMOQZ-UHFFFAOYSA-N 0.000 description 2
• YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
• YAJGKCZOZXZUOG-UHFFFAOYSA-N 4-[1-(4-bromophenyl)-2-(methylamino)ethyl]phenol Chemical compound C=1C=C(Br)C=CC=1C(CNC)C1=CC=C(O)C=C1 YAJGKCZOZXZUOG-UHFFFAOYSA-N 0.000 description 2
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
• ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 2
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 2
• AAQFMGLCMDYAOZ-UHFFFAOYSA-N 6-(3-methyl-1-tritylpyrazol-4-yl)pyridine-3-carbonitrile Chemical compound CC1=NN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1C1=CC=C(C#N)C=N1 AAQFMGLCMDYAOZ-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• XKJMBINCVNINCA-UHFFFAOYSA-N Alfalone Chemical compound CON(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XKJMBINCVNINCA-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 229920001651 Cyanoacrylate Polymers 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 102000001301 EGF receptor Human genes 0.000 description 2
• 108060006698 EGF receptor Proteins 0.000 description 2
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
• 108091008794 FGF receptors Proteins 0.000 description 2
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma 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
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• 102000004310 Ion Channels Human genes 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• JQGPBDSMTHZOMO-UHFFFAOYSA-N OBO.C=1C=NNC=1 Chemical compound OBO.C=1C=NNC=1 JQGPBDSMTHZOMO-UHFFFAOYSA-N 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 108091008606 PDGF receptors Proteins 0.000 description 2
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
• 229910000564 Raney nickel Inorganic materials 0.000 description 2
• 229910004298 SiO 2 Inorganic materials 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• 150000007960 acetonitrile Chemical class 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
• KZNCFIIFMFCSHL-UHFFFAOYSA-N benzyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)NC(C)C(=O)OCC1=CC=CC=C1 KZNCFIIFMFCSHL-UHFFFAOYSA-N 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052796 boron Inorganic materials 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 230000032823 cell division Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 238000006482 condensation reaction Methods 0.000 description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
• 238000006114 decarboxylation reaction Methods 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• 238000002405 diagnostic procedure Methods 0.000 description 2
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical group C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
• 238000003821 enantio-separation Methods 0.000 description 2
• 238000004146 energy storage Methods 0.000 description 2
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
• PACGICOUEJZOPW-UHFFFAOYSA-N ethyl 3-(4-bromophenyl)-3-(4-chlorophenyl)-2-cyanopropanoate Chemical compound C=1C=C(Br)C=CC=1C(C(C#N)C(=O)OCC)C1=CC=C(Cl)C=C1 PACGICOUEJZOPW-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 108091006104 gene-regulatory proteins Proteins 0.000 description 2
• 102000034356 gene-regulatory proteins Human genes 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 125000000468 ketone group Chemical group 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• RMXGWLUCCKWPGK-UHFFFAOYSA-M magnesium;1,2-dichlorobenzene-5-ide;bromide Chemical compound [Mg+2].[Br-].ClC1=CC=[C-]C=C1Cl RMXGWLUCCKWPGK-UHFFFAOYSA-M 0.000 description 2
• QCFRAUYDPLRPCI-UHFFFAOYSA-M magnesium;1-methanidyl-4-methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=C([CH2-])C=C1 QCFRAUYDPLRPCI-UHFFFAOYSA-M 0.000 description 2
• ZMPYQGQHGLLBQI-UHFFFAOYSA-M magnesium;chlorobenzene;bromide Chemical compound [Mg+2].[Br-].ClC1=CC=C[C-]=C1 ZMPYQGQHGLLBQI-UHFFFAOYSA-M 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
• KXQSTXDOVLZJKQ-UHFFFAOYSA-N methyl 2,2-bis(4-chlorophenyl)propanoate Chemical compound C=1C=C(Cl)C=CC=1C(C)(C(=O)OC)C1=CC=C(Cl)C=C1 KXQSTXDOVLZJKQ-UHFFFAOYSA-N 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000006199 nebulizer Substances 0.000 description 2
• 230000009826 neoplastic cell growth Effects 0.000 description 2
• 125000002560 nitrile group Chemical group 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 2
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
• 150000002989 phenols Chemical class 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000000861 pro-apoptotic effect Effects 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 210000005267 prostate cell Anatomy 0.000 description 2
• 239000003197 protein kinase B inhibitor Substances 0.000 description 2
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 229910052701 rubidium Inorganic materials 0.000 description 2
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 150000003456 sulfonamides Chemical class 0.000 description 2
• 235000011149 sulphuric acid Nutrition 0.000 description 2
• 230000004654 survival pathway Effects 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• FKSHHLBULFBFLH-UHFFFAOYSA-N tert-butyl 4-(4-bromophenyl)-4-[4-(2-methoxyethoxy)phenyl]piperidine-1-carboxylate Chemical compound C1=CC(OCCOC)=CC=C1C1(C=2C=CC(Br)=CC=2)CCN(C(=O)OC(C)(C)C)CC1 FKSHHLBULFBFLH-UHFFFAOYSA-N 0.000 description 2
• 150000003568 thioethers Chemical class 0.000 description 2
• 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• 235000012431 wafers Nutrition 0.000 description 2
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
• YMEUBHUXXVUFID-UHFFFAOYSA-N (4-chlorophenyl)-(4-iodophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=C(I)C=C1 YMEUBHUXXVUFID-UHFFFAOYSA-N 0.000 description 1
• LUAAXIJQXNSKGX-UHFFFAOYSA-N (4-chlorophenyl)-[6-(3-methyl-1-tritylpyrazol-4-yl)pyridin-3-yl]methanone Chemical compound CC1=NN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1C(N=C1)=CC=C1C(=O)C1=CC=C(Cl)C=C1 LUAAXIJQXNSKGX-UHFFFAOYSA-N 0.000 description 1
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
• CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• CFMMTXJMIJRUSH-UHFFFAOYSA-N 1-(4-bromophenyl)propan-2-one Chemical compound CC(=O)CC1=CC=C(Br)C=C1 CFMMTXJMIJRUSH-UHFFFAOYSA-N 0.000 description 1
• JYDHZOIDIWUHDB-UHFFFAOYSA-N 1-(4-phenylpiperidin-4-yl)ethanone;hydrochloride Chemical group Cl.C=1C=CC=CC=1C1(C(=O)C)CCNCC1 JYDHZOIDIWUHDB-UHFFFAOYSA-N 0.000 description 1
• BDIJPBVLZALCFW-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]-4-methyl-1,4-diazepan-4-ium;chloride Chemical compound [Cl-].C1C[NH+](C)CCCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 BDIJPBVLZALCFW-UHFFFAOYSA-N 0.000 description 1
• BCIBADNRBANBEW-UHFFFAOYSA-N 1-[2,2-bis(4-chlorophenyl)ethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)CN1CCNCC1 BCIBADNRBANBEW-UHFFFAOYSA-N 0.000 description 1
• PVPLCPMPSGIRSI-UHFFFAOYSA-N 1-[3-(4-bromophenyl)-3-(4-chlorophenyl)propyl]imidazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Br)=CC=1)CCN1C=NC=C1 PVPLCPMPSGIRSI-UHFFFAOYSA-N 0.000 description 1
• LCQXROFSCQEKMY-UHFFFAOYSA-N 1-[3-(4-bromophenyl)-3-phenoxypropyl]imidazole Chemical compound C1=CC(Br)=CC=C1C(OC=1C=CC=CC=1)CCN1C=NC=C1 LCQXROFSCQEKMY-UHFFFAOYSA-N 0.000 description 1
• HEJXJZAGWFPZHN-UHFFFAOYSA-N 1-[4-[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]phenyl]-3-phenylpropan-2-amine Chemical compound N1N=C(C(F)(F)F)C(C=2C=CC(CC(N)CC=3C=CC=CC=3)=CC=2)=C1C HEJXJZAGWFPZHN-UHFFFAOYSA-N 0.000 description 1
• PTLFMGDNZYQISN-UHFFFAOYSA-N 1-[bis(4-chlorophenyl)methyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)N1CCNCC1 PTLFMGDNZYQISN-UHFFFAOYSA-N 0.000 description 1
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
• AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
• ALBNOJHFBUICLB-UHFFFAOYSA-N 1-phenyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=CC=CC=1C(N)CC(C=C1)=CC=C1C=1C=NNC=1 ALBNOJHFBUICLB-UHFFFAOYSA-N 0.000 description 1
• WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• VZLKQEPNZIWSFF-UHFFFAOYSA-N 1-pyrrolidin-1-ylpiperidine Chemical compound C1CCCN1N1CCCCC1 VZLKQEPNZIWSFF-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
• AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical group C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• LYXZQUGNMPVGRS-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)-n,n-dimethylacetamide Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)N(C)C)C1=CC=C(Cl)C=C1 LYXZQUGNMPVGRS-UHFFFAOYSA-N 0.000 description 1
• YSFPMDGNOAHTTQ-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)-n-methylpropan-1-amine Chemical compound C=1C=C(Cl)C=CC=1C(C)(CNC)C1=CC=C(Cl)C=C1 YSFPMDGNOAHTTQ-UHFFFAOYSA-N 0.000 description 1
• KDDFOSJQPZKUJZ-UHFFFAOYSA-N 2,2-bis(4-chlorophenyl)ethanamine Chemical compound C=1C=C(Cl)C=CC=1C(CN)C1=CC=C(Cl)C=C1 KDDFOSJQPZKUJZ-UHFFFAOYSA-N 0.000 description 1
• HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
• OYJGEOAXBALSMM-UHFFFAOYSA-N 2,3-dihydro-1,3-thiazole Chemical compound C1NC=CS1 OYJGEOAXBALSMM-UHFFFAOYSA-N 0.000 description 1
• MWFLUYFYHANMCM-UHFFFAOYSA-N 2-(2-hydroxyethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCO)C(=O)C2=C1 MWFLUYFYHANMCM-UHFFFAOYSA-N 0.000 description 1
• RZQSUNKASWLJQA-UHFFFAOYSA-N 2-(3-chlorophenoxy)-n-methyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNC)OC1=CC=CC(Cl)=C1 RZQSUNKASWLJQA-UHFFFAOYSA-N 0.000 description 1
• UFICLMKYXIECIQ-UHFFFAOYSA-N 2-(4-bromophenyl)-2-(4-chlorophenyl)-n-ethylethanamine Chemical compound C=1C=C(Br)C=CC=1C(CNCC)C1=CC=C(Cl)C=C1 UFICLMKYXIECIQ-UHFFFAOYSA-N 0.000 description 1
• VTEAULOXLZLNME-UHFFFAOYSA-N 2-(4-bromophenyl)-3-phenylpropanenitrile Chemical group C1=CC(Br)=CC=C1C(C#N)CC1=CC=CC=C1 VTEAULOXLZLNME-UHFFFAOYSA-N 0.000 description 1
• YXAPARTWKCFYAE-UHFFFAOYSA-N 2-(4-bromophenyl)-n-methyl-2-(4-phenoxyphenyl)ethanamine Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1C(CNC)C1=CC=C(Br)C=C1 YXAPARTWKCFYAE-UHFFFAOYSA-N 0.000 description 1
• AVSIOYBNMUXBLV-UHFFFAOYSA-N 2-(4-bromophenyl)-n-methyl-2-(4-pyrazin-2-yloxyphenyl)ethanamine Chemical compound C=1C=C(OC=2N=CC=NC=2)C=CC=1C(CNC)C1=CC=C(Br)C=C1 AVSIOYBNMUXBLV-UHFFFAOYSA-N 0.000 description 1
• BFUMYLPYIWPJRZ-UHFFFAOYSA-N 2-(4-bromophenyl)-n-methyl-2-phenoxyethanamine Chemical compound C=1C=C(Br)C=CC=1C(CNC)OC1=CC=CC=C1 BFUMYLPYIWPJRZ-UHFFFAOYSA-N 0.000 description 1
• MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 1
• NNINSLOEPXEZOZ-UHFFFAOYSA-N 2-(4-bromophenyl)oxirane Chemical compound C1=CC(Br)=CC=C1C1OC1 NNINSLOEPXEZOZ-UHFFFAOYSA-N 0.000 description 1
• XMRGJITVFDERNT-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(4-iodophenyl)morpholine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(I)=CC=2)OCCNC1 XMRGJITVFDERNT-UHFFFAOYSA-N 0.000 description 1
• PHFKKUIVIIPBAI-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]acetaldehyde Chemical compound C1=CC(Cl)=CC=C1C(C=O)C1=CC=C(C2=CNN=C2)C=C1 PHFKKUIVIIPBAI-UHFFFAOYSA-N 0.000 description 1
• YTIXTVUIMQCOOX-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]acetamide Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(C(=O)N)C1=CC=C(Cl)C=C1 YTIXTVUIMQCOOX-UHFFFAOYSA-N 0.000 description 1
• CNKMDQTUJJUOBH-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-methyl-2-[6-(3-methyl-1-tritylpyrazol-4-yl)pyridin-3-yl]-n-(1-phenylethyl)ethenamine Chemical compound C=1C=CC=CC=1C(C)N(C)C=C(C=1C=NC(=CC=1)C=1C(=NN(C=1)C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)C)C1=CC=C(Cl)C=C1 CNKMDQTUJJUOBH-UHFFFAOYSA-N 0.000 description 1
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• BXXJGENYVURAQR-UHFFFAOYSA-N 2-[2-[(4-bromophenyl)-(4-chlorophenyl)methoxy]ethyl]isoindole-1,3-dione Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Br)=CC=1)OCCN1C(=O)C2=CC=CC=C2C1=O BXXJGENYVURAQR-UHFFFAOYSA-N 0.000 description 1
• XRMWCHWBHVNCNC-UHFFFAOYSA-N 2-[3-(1h-pyrazol-4-yl)phenyl]acetonitrile Chemical compound N#CCC1=CC=CC(C2=CNN=C2)=C1 XRMWCHWBHVNCNC-UHFFFAOYSA-N 0.000 description 1
• RQEFJCHYIXFXEO-UHFFFAOYSA-N 2-[4-(5-methyl-1h-pyrazol-4-yl)phenyl]-2-phenylethanamine Chemical compound CC1=NNC=C1C1=CC=C(C(CN)C=2C=CC=CC=2)C=C1 RQEFJCHYIXFXEO-UHFFFAOYSA-N 0.000 description 1
• STGCUJKOESZGQS-UHFFFAOYSA-N 2-[4-[3-methyl-1-(oxan-2-yl)pyrazol-4-yl]phenyl]-2-phenylethanamine Chemical compound CC1=NN(C2OCCCC2)C=C1C(C=C1)=CC=C1C(CN)C1=CC=CC=C1 STGCUJKOESZGQS-UHFFFAOYSA-N 0.000 description 1
• BFFLGOKYQWOEHU-UHFFFAOYSA-N 2-[4-[5-methyl-1-(oxan-2-yl)-3-(trifluoromethyl)pyrazol-4-yl]phenyl]-3-phenylpropanenitrile Chemical compound CC1=C(C=2C=CC(=CC=2)C(CC=2C=CC=CC=2)C#N)C(C(F)(F)F)=NN1C1CCCCO1 BFFLGOKYQWOEHU-UHFFFAOYSA-N 0.000 description 1
• TYXNIYCXPUUFPT-UHFFFAOYSA-N 2-[4-[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]phenyl]-1-phenylethanamine Chemical compound N1N=C(C(F)(F)F)C(C=2C=CC(CC(N)C=3C=CC=CC=3)=CC=2)=C1C TYXNIYCXPUUFPT-UHFFFAOYSA-N 0.000 description 1
• HPPUYQKRXRMGJI-UHFFFAOYSA-N 2-[4-[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]phenyl]-3-phenylpropan-1-amine Chemical compound N1N=C(C(F)(F)F)C(C=2C=CC(=CC=2)C(CN)CC=2C=CC=CC=2)=C1C HPPUYQKRXRMGJI-UHFFFAOYSA-N 0.000 description 1
• SEBSRWXMUYLWDW-UHFFFAOYSA-N 2-[4-[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]phenyl]acetonitrile Chemical compound N1N=C(C(F)(F)F)C(C=2C=CC(CC#N)=CC=2)=C1C SEBSRWXMUYLWDW-UHFFFAOYSA-N 0.000 description 1
• NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical class C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
• UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
• QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
• WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 1
• DIWCDMHFVAOTCR-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-n-methyl-3-[4-(1h-pyrazol-4-yl)phenyl]propanamide Chemical compound C=1C=C(F)C(F)=CC=1C(CC(=O)NC)C(C=C1)=CC=C1C=1C=NNC=1 DIWCDMHFVAOTCR-UHFFFAOYSA-N 0.000 description 1
• XEMDFESAXKSEGI-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CN=C1 XEMDFESAXKSEGI-UHFFFAOYSA-N 0.000 description 1
• WHHXGILMTJNKIE-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(3-chlorophenoxy)-n-methylpropan-1-amine Chemical compound C=1C=C(Br)C=CC=1C(CCNC)OC1=CC=CC(Cl)=C1 WHHXGILMTJNKIE-UHFFFAOYSA-N 0.000 description 1
• CABCIMZURWFWFM-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-chlorophenyl)-n-methylpropan-1-amine Chemical compound C=1C=C(Br)C=CC=1C(CCNC)C1=CC=C(Cl)C=C1 CABCIMZURWFWFM-UHFFFAOYSA-N 0.000 description 1
• VJZZMVWCBMZMTC-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-chlorophenyl)propanamide Chemical compound C=1C=C(Br)C=CC=1C(CC(=O)N)C1=CC=C(Cl)C=C1 VJZZMVWCBMZMTC-UHFFFAOYSA-N 0.000 description 1
• ASNHBIOMMPKUCJ-UHFFFAOYSA-N 3-(4-bromophenyl)-3-(4-fluorophenyl)propanoic acid Chemical compound C=1C=C(Br)C=CC=1C(CC(=O)O)C1=CC=C(F)C=C1 ASNHBIOMMPKUCJ-UHFFFAOYSA-N 0.000 description 1
• QLJLUDCLPSRPFI-UHFFFAOYSA-N 3-[[2-(4-chlorophenyl)-2-[4-(1h-pyrazol-4-yl)phenyl]ethyl]amino]propan-1-ol Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CNCCCO)C1=CC=C(Cl)C=C1 QLJLUDCLPSRPFI-UHFFFAOYSA-N 0.000 description 1
• HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 description 1
• JDFDHBSESGTDAL-UHFFFAOYSA-N 3-methoxypropan-1-ol Chemical compound COCCCO JDFDHBSESGTDAL-UHFFFAOYSA-N 0.000 description 1
• XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
• YCVAGNVTZICLNM-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzofuran Chemical compound C1CCCC2=C1C=CO2 YCVAGNVTZICLNM-UHFFFAOYSA-N 0.000 description 1
• MJWJFFSKNOOQFZ-UHFFFAOYSA-N 4-(4-bromophenyl)-4-(4-chlorophenyl)piperidine;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C1(C=2C=CC(Br)=CC=2)CCNCC1 MJWJFFSKNOOQFZ-UHFFFAOYSA-N 0.000 description 1
• QNLXJYQUWCNYBH-UHFFFAOYSA-N 4-(4-bromophenyl)piperidin-4-ol Chemical compound C=1C=C(Br)C=CC=1C1(O)CCNCC1 QNLXJYQUWCNYBH-UHFFFAOYSA-N 0.000 description 1
• FVJZMDKZNWUQCO-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-(4-iodophenyl)piperidine Chemical compound C1=CC(Cl)=CC=C1C1(C=2C=CC(I)=CC=2)CCNCC1 FVJZMDKZNWUQCO-UHFFFAOYSA-N 0.000 description 1
• PQFSNVZECRYZDW-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-[4-(3-methyl-1-tritylpyrazol-4-yl)phenyl]piperidine Chemical compound CC1=NN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1C(C=C1)=CC=C1C1(C=2C=CC(Cl)=CC=2)CCNCC1 PQFSNVZECRYZDW-UHFFFAOYSA-N 0.000 description 1
• GJUCYUSBYRIQMF-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperidine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C2(CCNCC2)C=2C=CC(Cl)=CC=2)C=C1 GJUCYUSBYRIQMF-UHFFFAOYSA-N 0.000 description 1
• GVBDZLGRVUJEFW-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-[4-(5-methyl-1h-pyrazol-4-yl)phenyl]piperidine Chemical compound CC1=NNC=C1C1=CC=C(C2(CCNCC2)C=2C=CC(Cl)=CC=2)C=C1 GVBDZLGRVUJEFW-UHFFFAOYSA-N 0.000 description 1
• LQLJNIMZZWZZLE-UHFFFAOYSA-N 4-(iminomethylideneamino)-n,n-dimethylpentan-1-amine;hydrochloride Chemical compound Cl.N=C=NC(C)CCCN(C)C LQLJNIMZZWZZLE-UHFFFAOYSA-N 0.000 description 1
• JDQHJOPZQIJCEA-UHFFFAOYSA-N 4-[4-(3-methoxypropoxy)phenyl]-4-[4-(1h-pyrazol-4-yl)phenyl]piperidine Chemical compound C1=CC(OCCCOC)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 JDQHJOPZQIJCEA-UHFFFAOYSA-N 0.000 description 1
• FYHSNVLCJJIDBN-UHFFFAOYSA-N 4-[4-(4-bromophenyl)piperidin-4-yl]phenol Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(Br)=CC=2)CCNCC1 FYHSNVLCJJIDBN-UHFFFAOYSA-N 0.000 description 1
• HLBRXOVHXRAVBQ-UHFFFAOYSA-N 4-[4-[1-(4-chlorophenyl)-2-pyrrolidin-1-ylethyl]phenyl]-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(=CC=1)C1=CNN=C1)CN1CCCC1 HLBRXOVHXRAVBQ-UHFFFAOYSA-N 0.000 description 1
• VBIDRMWBZZTFRK-UHFFFAOYSA-N 4-[4-[4-(1h-pyrazol-4-yl)phenyl]piperidin-4-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1(C=2C=CC(=CC=2)C2=CNN=C2)CCNCC1 VBIDRMWBZZTFRK-UHFFFAOYSA-N 0.000 description 1
• DEUZQAZONXREGN-UHFFFAOYSA-N 4-[4-[4-(1h-pyrazol-4-yl)phenyl]piperidin-4-yl]pyridine Chemical group C1CNCCC1(C=1C=CC(=CC=1)C1=CNN=C1)C1=CC=NC=C1 DEUZQAZONXREGN-UHFFFAOYSA-N 0.000 description 1
• ZXVFKQRZKKGVNJ-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carbonitrile Chemical compound BrC=1C=NNC=1C#N ZXVFKQRZKKGVNJ-UHFFFAOYSA-N 0.000 description 1
• GAOXIBSDLFALAS-UHFFFAOYSA-N 4-bromo-5-methyl-1-(oxan-2-yl)-3-(trifluoromethyl)pyrazole Chemical compound CC1=C(Br)C(C(F)(F)F)=NN1C1OCCCC1 GAOXIBSDLFALAS-UHFFFAOYSA-N 0.000 description 1
• PDSOUBXNWWZCNB-UHFFFAOYSA-N 4-bromo-5-methyl-3-(trifluoromethyl)-1h-pyrazole Chemical compound CC=1NN=C(C(F)(F)F)C=1Br PDSOUBXNWWZCNB-UHFFFAOYSA-N 0.000 description 1
• WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
• WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical group OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• ORIQLMBUPMABDV-UHFFFAOYSA-N 6-chloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C=N1 ORIQLMBUPMABDV-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 101100297694 Arabidopsis thaliana PIP2-7 gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• JTNOEBCRBCPYGJ-GOSISDBHSA-N C1(=CC=CC=C1)C([PH2]=O)(C1=CC=CC=C1)N([C@H](C)C1=CC=CC=C1)C Chemical compound C1(=CC=CC=C1)C([PH2]=O)(C1=CC=CC=C1)N([C@H](C)C1=CC=CC=C1)C JTNOEBCRBCPYGJ-GOSISDBHSA-N 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• 229940126074 CDK kinase inhibitor Drugs 0.000 description 1
• 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 102100026550 Caspase-9 Human genes 0.000 description 1
• 108090000566 Caspase-9 Proteins 0.000 description 1
• 241001227713 Chiron Species 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 101150065749 Churc1 gene Proteins 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
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 241001634576 Colona Species 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• 102100034770 Cyclin-dependent kinase inhibitor 3 Human genes 0.000 description 1
• PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 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
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 102100021238 Dynamin-2 Human genes 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 102100030013 Endoribonuclease Human genes 0.000 description 1
• 101710199605 Endoribonuclease Proteins 0.000 description 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• 108090000852 Forkhead Transcription Factors Proteins 0.000 description 1
• 102100035427 Forkhead box protein O1 Human genes 0.000 description 1
• 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
• 102000051325 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 108010001483 Glycogen Synthase Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 108010025076 Holoenzymes Proteins 0.000 description 1
• 101000945639 Homo sapiens Cyclin-dependent kinase inhibitor 3 Proteins 0.000 description 1
• 101000817607 Homo sapiens Dynamin-2 Proteins 0.000 description 1
• 101000877727 Homo sapiens Forkhead box protein O1 Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 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 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 206010022489 Insulin Resistance Diseases 0.000 description 1
• 102000000588 Interleukin-2 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 208000032382 Ischaemic stroke Diseases 0.000 description 1
• 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
• 102000016397 Methyltransferase Human genes 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 238000006845 Michael addition reaction Methods 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000021642 Muscular disease Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 201000009623 Myopathy Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-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
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
• VYEAHXRPWKOEMY-UHFFFAOYSA-N O-(9H-fluoren-9-ylmethyl)hydroxylamine Chemical compound C1=CC=C2C(CON)C3=CC=CC=C3C2=C1 VYEAHXRPWKOEMY-UHFFFAOYSA-N 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 101150107050 PSA2 gene Proteins 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
• BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 102000014750 Phosphorylase Kinase Human genes 0.000 description 1
• 108010064071 Phosphorylase Kinase Proteins 0.000 description 1
• 108010073135 Phosphorylases Proteins 0.000 description 1
• 102000009097 Phosphorylases Human genes 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
• 102100038239 Protein Churchill Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 101100456541 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MEC3 gene Proteins 0.000 description 1
• 101100483663 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UFD1 gene Proteins 0.000 description 1
• 101001117144 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) [Pyruvate dehydrogenase (acetyl-transferring)] kinase 1, mitochondrial Proteins 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 102000004584 Somatomedin Receptors Human genes 0.000 description 1
• 108010017622 Somatomedin Receptors Proteins 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 108091008605 VEGF receptors Proteins 0.000 description 1
• 244000126014 Valeriana officinalis Species 0.000 description 1
• 235000013832 Valeriana officinalis Nutrition 0.000 description 1
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 125000005042 acyloxymethyl group Chemical group 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 108060000200 adenylate cyclase Proteins 0.000 description 1
• 102000030621 adenylate cyclase Human genes 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 125000002723 alicyclic group Chemical group 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 201000009961 allergic asthma Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 238000010976 amide bond formation reaction Methods 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 229940051880 analgesics and antipyretics pyrazolones Drugs 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000012223 aqueous fraction Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 150000008378 aryl ethers Chemical class 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
• 210000003567 ascitic fluid Anatomy 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
• JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 150000001556 benzimidazoles Chemical class 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
• JZXGNEDXFODMIJ-UHFFFAOYSA-N benzyl n-[2-(4-bromophenyl)-2-(4-fluorophenyl)ethyl]carbamate Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(Br)=CC=1)CNC(=O)OCC1=CC=CC=C1 JZXGNEDXFODMIJ-UHFFFAOYSA-N 0.000 description 1
• RRIWSQXXBIFKQM-UHFFFAOYSA-N benzylcarbamic acid Chemical group OC(=O)NCC1=CC=CC=C1 RRIWSQXXBIFKQM-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical group BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
• 125000005998 bromoethyl group Chemical group 0.000 description 1
• 125000004799 bromophenyl group Chemical group 0.000 description 1
• SRGKFVAASLQVBO-BTJKTKAUSA-N brompheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 SRGKFVAASLQVBO-BTJKTKAUSA-N 0.000 description 1
• 229960003108 brompheniramine maleate Drugs 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229930188620 butyrolactone Natural products 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 239000007963 capsule composition Substances 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• JJWKPURADFRFRB-UHFFFAOYSA-N carbonyl sulfide Chemical compound O=C=S JJWKPURADFRFRB-UHFFFAOYSA-N 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 239000003729 cation exchange resin Substances 0.000 description 1
• 229940023913 cation exchange resins Drugs 0.000 description 1
• 150000001767 cationic compounds Chemical class 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000009134 cell regulation Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 description 1
• 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
• 239000013611 chromosomal DNA Substances 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 239000007979 citrate buffer Substances 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004802 cyanophenyl group Chemical group 0.000 description 1
• 150000003950 cyclic amides Chemical group 0.000 description 1
• 239000002755 cyclic amp dependent protein kinase inhibitor Substances 0.000 description 1
• 150000001923 cyclic compounds Chemical class 0.000 description 1
• 150000004292 cyclic ethers Chemical group 0.000 description 1
• 150000004294 cyclic thioethers Chemical group 0.000 description 1
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
• 150000001924 cycloalkanes Chemical class 0.000 description 1
• 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
• KDUIUFJBNGTBMD-VXMYFEMYSA-N cyclooctatetraene Chemical compound C1=C\C=C/C=C\C=C1 KDUIUFJBNGTBMD-VXMYFEMYSA-N 0.000 description 1
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000009849 deactivation Effects 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 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 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 125000004212 difluorophenyl group Chemical group 0.000 description 1
• IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 description 1
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• IWXAQMPHDLOLAH-UHFFFAOYSA-N diphenylphosphorylmethanamine Chemical compound C=1C=CC=CC=1P(=O)(CN)C1=CC=CC=C1 IWXAQMPHDLOLAH-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 230000008143 early embryonic development Effects 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 102000015694 estrogen receptors Human genes 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• NHGHYWZQJLQGJY-UHFFFAOYSA-N ethyl 2-[4-[4-(4-bromophenyl)piperidin-4-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C1(C=2C=CC(Br)=CC=2)CCNCC1 NHGHYWZQJLQGJY-UHFFFAOYSA-N 0.000 description 1
• MJGTUYOCBQBORS-UHFFFAOYSA-N ethyl 3-(4-bromophenyl)-2-cyanoprop-2-enoate Chemical compound CCOC(=O)C(C#N)=CC1=CC=C(Br)C=C1 MJGTUYOCBQBORS-UHFFFAOYSA-N 0.000 description 1
• QJGRQWWEJMVSSC-UHFFFAOYSA-N ethyl 4-(4-bromophenyl)-4-(4-chlorophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1(C=1C=CC(Br)=CC=1)C1=CC=C(Cl)C=C1 QJGRQWWEJMVSSC-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 210000003020 exocrine pancreas Anatomy 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000007888 film coating Substances 0.000 description 1
• 238000009501 film coating Methods 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 239000002223 garnet Substances 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
• 229960004666 glucagon Drugs 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 125000003106 haloaryl group Chemical group 0.000 description 1
• 150000005171 halobenzenes Chemical class 0.000 description 1
• 125000005216 haloheteroaryl group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
• 230000037417 hyperactivation Effects 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 238000003018 immunoassay Methods 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 230000006882 induction of apoptosis Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910001411 inorganic cation Inorganic materials 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• SNHMUERNLJLMHN-IDEBNGHGSA-N iodobenzene Chemical group I[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 SNHMUERNLJLMHN-IDEBNGHGSA-N 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical group CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• HMORFZOLRLQTTR-UHFFFAOYSA-M magnesium;1-bromo-4-methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=C(Br)C=C1 HMORFZOLRLQTTR-UHFFFAOYSA-M 0.000 description 1
• YLVLCBHNULZXLQ-UHFFFAOYSA-M magnesium;2h-naphthalen-2-ide;bromide Chemical group [Mg+2].[Br-].C1=[C-]C=CC2=CC=CC=C21 YLVLCBHNULZXLQ-UHFFFAOYSA-M 0.000 description 1
• QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
• OFDIPUNYMRLSER-UHFFFAOYSA-M magnesium;n,n-dimethylaniline;bromide Chemical group [Mg+2].[Br-].CN(C)C1=CC=[C-]C=C1 OFDIPUNYMRLSER-UHFFFAOYSA-M 0.000 description 1
• MPMNUCMJDPWNCV-UHFFFAOYSA-M magnesium;phenoxybenzene;bromide Chemical compound [Mg+2].[Br-].C=1C=[C-]C=CC=1OC1=CC=CC=C1 MPMNUCMJDPWNCV-UHFFFAOYSA-M 0.000 description 1
• FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• 150000005573 methoxybenzenes Chemical class 0.000 description 1
• FIHLIVMWNUSLRU-UHFFFAOYSA-N methyl 2,2-bis(4-chlorophenyl)acetate Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)OC)C1=CC=C(Cl)C=C1 FIHLIVMWNUSLRU-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
• 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 230000000869 mutational effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• PJCLMNOZUMMYTJ-UHFFFAOYSA-N n,n-dimethyl-2-phenyl-2-[4-(1h-pyrazol-4-yl)phenyl]ethanamine Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CN(C)C)C1=CC=CC=C1 PJCLMNOZUMMYTJ-UHFFFAOYSA-N 0.000 description 1
• YCAFDYGANIWYNW-UHFFFAOYSA-N n,n-dimethyl-4-[3-(methylamino)-1-[4-(1h-pyrazol-4-yl)phenyl]propyl]aniline Chemical compound C=1C=C(C2=CNN=C2)C=CC=1C(CCNC)C1=CC=C(N(C)C)C=C1 YCAFDYGANIWYNW-UHFFFAOYSA-N 0.000 description 1
• MRHQBBSKCLIMRH-UHFFFAOYSA-N n-(acetamidomethoxymethyl)acetamide Chemical compound CC(=O)NCOCNC(C)=O MRHQBBSKCLIMRH-UHFFFAOYSA-N 0.000 description 1
• GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• RCSSHZGQHHEHPZ-UHFFFAOYSA-N n-methyl-1-phenylethanamine Chemical compound CNC(C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-UHFFFAOYSA-N 0.000 description 1
• OIWAUZXCTYOMCK-UHFFFAOYSA-N n-methyl-6-phenoxy-6-[4-(1h-pyrazol-4-yl)phenyl]cyclohexa-2,4-dien-1-amine Chemical compound CNC1C=CC=CC1(C=1C=CC(=CC=1)C1=CNN=C1)OC1=CC=CC=C1 OIWAUZXCTYOMCK-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 230000001338 necrotic effect Effects 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000003957 neurotransmitter release Effects 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 108020004017 nuclear receptors Proteins 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 235000016709 nutrition Nutrition 0.000 description 1
• LUHFJLLCZSYACL-UHFFFAOYSA-N o-(2,2,2-trichloroethyl)hydroxylamine Chemical compound NOCC(Cl)(Cl)Cl LUHFJLLCZSYACL-UHFFFAOYSA-N 0.000 description 1
• GWCBVFMHGHMALR-UHFFFAOYSA-N o-(2-trimethylsilylethyl)hydroxylamine Chemical compound C[Si](C)(C)CCON GWCBVFMHGHMALR-UHFFFAOYSA-N 0.000 description 1
• HFMYNBFAXIDOIO-UHFFFAOYSA-N o-[2-(benzenesulfonyl)ethyl]hydroxylamine Chemical compound NOCCS(=O)(=O)C1=CC=CC=C1 HFMYNBFAXIDOIO-UHFFFAOYSA-N 0.000 description 1
• XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
• KKVUFSINQFSJNK-UHFFFAOYSA-N o-tert-butylhydroxylamine Chemical compound CC(C)(C)ON KKVUFSINQFSJNK-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 229940127084 other anti-cancer agent Drugs 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• CQDAMYNQINDRQC-UHFFFAOYSA-N oxatriazole Chemical compound C1=NN=NO1 CQDAMYNQINDRQC-UHFFFAOYSA-N 0.000 description 1
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical class C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• 229950010364 phenpromethamine Drugs 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 238000002428 photodynamic therapy Methods 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 125000005543 phthalimide group Chemical group 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
• 210000004910 pleural fluid Anatomy 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 239000002157 polynucleotide Substances 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 230000016833 positive regulation of signal transduction Effects 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000004262 preparative liquid chromatography Methods 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 229940043437 protein kinase A inhibitor Drugs 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 230000004850 protein–protein interaction Effects 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 229910052705 radium Inorganic materials 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 230000004188 regulation of glucose levels Effects 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 230000007076 release of cytoplasmic sequestered NF-kappaB Effects 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 206010039083 rhinitis Diseases 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 206010039667 schwannoma Diseases 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 230000008054 signal transmission Effects 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008227 sterile water for injection Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 125000005504 styryl group Chemical group 0.000 description 1
• 239000006190 sub-lingual tablet Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000005156 substituted alkylene group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 238000000967 suction filtration Methods 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical group NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
• MBDNRNMVTZADMQ-UHFFFAOYSA-N sulfolene Chemical compound O=S1(=O)CC=CC1 MBDNRNMVTZADMQ-UHFFFAOYSA-N 0.000 description 1
• 150000003457 sulfones Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• AYRCQEYIRSRBFV-UHFFFAOYSA-N tert-butyl 4-(4-bromophenyl)-4-(4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C=1C=CC(Br)=CC=1)C1=CC=C(O)C=C1 AYRCQEYIRSRBFV-UHFFFAOYSA-N 0.000 description 1
• JPZNXPLBQAITHI-UHFFFAOYSA-N tert-butyl 4-(4-bromophenyl)-4-[4-(3-methoxypropoxy)phenyl]piperidine-1-carboxylate Chemical compound C1=CC(OCCCOC)=CC=C1C1(C=2C=CC(Br)=CC=2)CCN(C(=O)OC(C)(C)C)CC1 JPZNXPLBQAITHI-UHFFFAOYSA-N 0.000 description 1
• NZTXNQCBJPCVMR-UHFFFAOYSA-N tert-butyl 4-[2,2-bis(4-chlorophenyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 NZTXNQCBJPCVMR-UHFFFAOYSA-N 0.000 description 1
• LLNFGZBTKPDBCT-UHFFFAOYSA-N tert-butyl n-[2-(4-bromophenyl)-2-(4-hydroxyphenyl)ethyl]-n-methylcarbamate Chemical compound C=1C=C(Br)C=CC=1C(CN(C)C(=O)OC(C)(C)C)C1=CC=C(O)C=C1 LLNFGZBTKPDBCT-UHFFFAOYSA-N 0.000 description 1
• DFTKQDLKQXTTKT-UHFFFAOYSA-N tert-butyl n-[2-(4-bromophenyl)-2-hydroxyethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC(O)C1=CC=C(Br)C=C1 DFTKQDLKQXTTKT-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical group 0.000 description 1
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• 150000003556 thioamides Chemical class 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 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
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical group OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
• 235000019798 tripotassium phosphate Nutrition 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 239000000225 tumor suppressor protein Substances 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 208000011479 upper respiratory tract disease Diseases 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 125000005500 uronium group Chemical group 0.000 description 1
• 235000016788 valerian Nutrition 0.000 description 1
• 239000002966 varnish Substances 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1