SK7022003A3 - Pyrazinoquinoxaline derivatives as serotonin agonists and antagonists - Google Patents

Info

Publication number

SK7022003A3

SK7022003A3 SK702-2003A SK7022003A SK7022003A3 SK 7022003 A3 SK7022003 A3 SK 7022003A3 SK 7022003 A SK7022003 A SK 7022003A SK 7022003 A3 SK7022003 A3 SK 7022003A3

Authority

SK

Slovakia

Prior art keywords

phenyl

substituted

alkyl

occurrence

independently selected

Prior art date

2000-12-20

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• 239000003420 antiserotonin agent Substances 0.000 title abstract description 7
• 239000000952 serotonin receptor agonist Substances 0.000 title abstract description 7
• CVSGFMWKZVZOJD-UHFFFAOYSA-N pyrazino[2,3-f]quinoxaline Chemical class C1=CN=C2C3=NC=CN=C3C=CC2=N1 CVSGFMWKZVZOJD-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 142
• 150000003839 salts Chemical class 0.000 claims abstract description 33
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 201000000980 schizophrenia Diseases 0.000 claims abstract description 13
• 208000008589 Obesity Diseases 0.000 claims abstract description 10
• 235000020824 obesity Nutrition 0.000 claims abstract description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• -1 2,3-dihydro-1H-inden-2-yl Chemical group 0.000 claims description 705
• MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims description 493
• 125000000217 alkyl group Chemical group 0.000 claims description 371
• 125000000304 alkynyl group Chemical group 0.000 claims description 166
• 229910052739 hydrogen Inorganic materials 0.000 claims description 162
• 125000003342 alkenyl group Chemical group 0.000 claims description 158
• VEAUDLLZYJVHRI-UHFFFAOYSA-N Trichlormethine Chemical compound Cl.ClCCN(CCCl)CCCl VEAUDLLZYJVHRI-UHFFFAOYSA-N 0.000 claims description 141
• 125000003118 aryl group Chemical group 0.000 claims description 134
• 229910052757 nitrogen Inorganic materials 0.000 claims description 132
• 229910052717 sulfur Inorganic materials 0.000 claims description 130
• 125000005842 heteroatom Chemical group 0.000 claims description 127
• 229910052760 oxygen Inorganic materials 0.000 claims description 125
• 125000000623 heterocyclic group Chemical group 0.000 claims description 121
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 113
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 112
• 125000003545 alkoxy group Chemical group 0.000 claims description 108
• 229910052736 halogen Inorganic materials 0.000 claims description 108
• 150000002367 halogens Chemical class 0.000 claims description 108
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
• 229910052799 carbon Inorganic materials 0.000 claims description 85
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 67
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 67
• 125000001188 haloalkyl group Chemical group 0.000 claims description 65
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 60
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 59
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 53
• 239000000460 chlorine Substances 0.000 claims description 50
• 238000000034 method Methods 0.000 claims description 47
• 229910052801 chlorine Inorganic materials 0.000 claims description 46
• 229910052731 fluorine Inorganic materials 0.000 claims description 46
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 44
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 43
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 42
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 41
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 24
• 125000002837 carbocyclic group Chemical group 0.000 claims description 24
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 21
• 125000001153 fluoro group Chemical group F* 0.000 claims description 20
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 18
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 14
• 125000004414 alkyl thio group Chemical group 0.000 claims description 14
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 claims description 13
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 13
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 12
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 claims description 12
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
• 229910052794 bromium Inorganic materials 0.000 claims description 12
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 12
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
• 125000001624 naphthyl group Chemical group 0.000 claims description 12
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 10
• 235000010290 biphenyl Nutrition 0.000 claims description 10
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 9
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 9
• 125000001041 indolyl group Chemical group 0.000 claims description 9
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 8
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 8
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 8
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 8
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
• 101150065749 Churc1 gene Proteins 0.000 claims description 8
• 102100038239 Protein Churchill Human genes 0.000 claims description 8
• 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 claims description 8
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 241000282414 Homo sapiens Species 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
• FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 claims description 6
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 6
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
• 125000005002 aryl methyl group Chemical group 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims description 5
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 5
• 125000005916 2-methylpentyl group Chemical group 0.000 claims description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 5
• 125000005917 3-methylpentyl group Chemical group 0.000 claims description 5
• 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 4
• 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 claims description 4
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 4
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
• RMAINTGPKFNBDP-UHFFFAOYSA-N 2-methylphenol Chemical group [CH2]C1=CC=CC=C1O RMAINTGPKFNBDP-UHFFFAOYSA-N 0.000 claims description 4
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 4
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 4
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 4
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 claims description 4
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 claims description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 4
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 4
• 239000002485 serotonin 2C agonist Substances 0.000 claims description 4
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
• 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 125000004125 inden-2-yl group Chemical group [H]C1=C(*)C([H])([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 16
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 1
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 1
• 239000004305 biphenyl Substances 0.000 claims 1
• 239000002484 serotonin 2C antagonist Substances 0.000 claims 1
• 125000003107 substituted aryl group Chemical group 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 17
• 238000011282 treatment Methods 0.000 abstract description 17
• 239000004480 active ingredient Substances 0.000 abstract description 13
• 208000019901 Anxiety disease Diseases 0.000 abstract description 12
• 230000036506 anxiety Effects 0.000 abstract description 12
• 208000019695 Migraine disease Diseases 0.000 abstract description 8
• 208000028017 Psychotic disease Diseases 0.000 abstract description 8
• 208000018522 Gastrointestinal disease Diseases 0.000 abstract description 7
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• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 36
• 238000006243 chemical reaction Methods 0.000 description 31
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
• 238000002360 preparation method Methods 0.000 description 21
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
• 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 16
• 108091005479 5-HT2 receptors Proteins 0.000 description 16
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• 230000000694 effects Effects 0.000 description 16
• 239000000243 solution Substances 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• 239000002253 acid Substances 0.000 description 13
• 150000003951 lactams Chemical class 0.000 description 13
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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• 238000003556 assay Methods 0.000 description 12
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• 238000003786 synthesis reaction Methods 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 235000019439 ethyl acetate Nutrition 0.000 description 10
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
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