AU2003264017B2 - Derivatives of 2-trifluormethyl-6-aminopurine as phosphodiesterase 4 inhibitors - Google Patents

Info

Publication number

AU2003264017B2

AU2003264017B2 AU2003264017A AU2003264017A AU2003264017B2 AU 2003264017 B2 AU2003264017 B2 AU 2003264017B2 AU 2003264017 A AU2003264017 A AU 2003264017A AU 2003264017 A AU2003264017 A AU 2003264017A AU 2003264017 B2 AU2003264017 B2 AU 2003264017B2

Authority

AU

Australia

Prior art keywords

alkyl

trifluoromethylpurine

alkoxy

halogenated

substituted

Prior art date

2002-08-08

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

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 12
• JPFOYYRMIMSYQZ-UHFFFAOYSA-N 2-(trifluoromethyl)-7h-purin-6-amine Chemical class NC1=NC(C(F)(F)F)=NC2=C1NC=N2 JPFOYYRMIMSYQZ-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 148
• 230000005764 inhibitory process Effects 0.000 claims abstract description 26
• 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims abstract 4
• 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims abstract 4
• 125000000217 alkyl group Chemical group 0.000 claims description 263
• -1 nitro, amino Chemical group 0.000 claims description 245
• 125000004432 carbon atom Chemical group C* 0.000 claims description 170
• 229910052736 halogen Inorganic materials 0.000 claims description 136
• 150000002367 halogens Chemical class 0.000 claims description 135
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 119
• 125000003545 alkoxy group Chemical group 0.000 claims description 117
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 98
• 125000006413 ring segment Chemical group 0.000 claims description 94
• 125000003118 aryl group Chemical group 0.000 claims description 88
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 75
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
• 238000000034 method Methods 0.000 claims description 66
• 125000001072 heteroaryl group Chemical group 0.000 claims description 61
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 58
• 125000004193 piperazinyl group Chemical group 0.000 claims description 54
• 125000003282 alkyl amino group Chemical group 0.000 claims description 52
• 125000002757 morpholinyl group Chemical group 0.000 claims description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
• 125000005842 heteroatom Chemical group 0.000 claims description 46
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 45
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 44
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 42
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
• 239000000203 mixture Substances 0.000 claims description 36
• 125000004043 oxo group Chemical group O=* 0.000 claims description 35
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 125000000623 heterocyclic group Chemical group 0.000 claims description 30
• 201000010099 disease Diseases 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 28
• YDAGLPIQWWSUJT-UHFFFAOYSA-N 2-(trifluoromethyl)-7h-purine Chemical compound FC(F)(F)C1=NC=C2NC=NC2=N1 YDAGLPIQWWSUJT-UHFFFAOYSA-N 0.000 claims description 25
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 23
• 230000000694 effects Effects 0.000 claims description 20
• 206010027175 memory impairment Diseases 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 18
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 16
• 102000004190 Enzymes Human genes 0.000 claims description 15
• 108090000790 Enzymes Proteins 0.000 claims description 15
• 125000004414 alkyl thio group Chemical group 0.000 claims description 15
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 230000003247 decreasing effect Effects 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 208000027866 inflammatory disease Diseases 0.000 claims description 10
• 208000028017 Psychotic disease Diseases 0.000 claims description 9
• 201000000980 schizophrenia Diseases 0.000 claims description 9
• 206010012289 Dementia Diseases 0.000 claims description 8
• 230000000172 allergic effect Effects 0.000 claims description 7
• 230000019771 cognition Effects 0.000 claims description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• 208000014674 injury Diseases 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• 208000027418 Wounds and injury Diseases 0.000 claims description 6
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
• 230000006378 damage Effects 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 5
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
• 208000023105 Huntington disease Diseases 0.000 claims description 5
• 208000018737 Parkinson disease Diseases 0.000 claims description 5
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 5
• 208000026935 allergic disease Diseases 0.000 claims description 5
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 206010013663 drug dependence Diseases 0.000 claims description 5
• 230000002708 enhancing effect Effects 0.000 claims description 5
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 208000008013 morphine dependence Diseases 0.000 claims description 5
• 230000004770 neurodegeneration Effects 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 5
• 208000011117 substance-related disease Diseases 0.000 claims description 5
• 208000020925 Bipolar disease Diseases 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 206010019196 Head injury Diseases 0.000 claims description 4
• 208000006011 Stroke Diseases 0.000 claims description 4
• 208000028683 bipolar I disease Diseases 0.000 claims description 4
• 230000007423 decrease Effects 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 206010021143 Hypoxia Diseases 0.000 claims description 3
• 230000007000 age related cognitive decline Effects 0.000 claims description 3
• 210000003169 central nervous system Anatomy 0.000 claims description 3
• 230000007954 hypoxia Effects 0.000 claims description 3
• 208000024714 major depressive disease Diseases 0.000 claims description 3
• DSJUVEXEQXMMNL-UHFFFAOYSA-N n-cyclopropyl-9-(2-piperazin-1-ylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3N=C(N=CC=3)N3CCNCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 DSJUVEXEQXMMNL-UHFFFAOYSA-N 0.000 claims description 3
• 206010003694 Atrophy Diseases 0.000 claims description 2
• 208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 2
• 201000004810 Vascular dementia Diseases 0.000 claims description 2
• 230000001154 acute effect Effects 0.000 claims description 2
• 230000032683 aging Effects 0.000 claims description 2
• 230000037444 atrophy Effects 0.000 claims description 2
• 208000025307 bipolar depression Diseases 0.000 claims description 2
• 230000002490 cerebral effect Effects 0.000 claims description 2
• 229910052740 iodine Inorganic materials 0.000 claims description 2
• 230000001537 neural effect Effects 0.000 claims description 2
• 208000020431 spinal cord injury Diseases 0.000 claims description 2
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims 2
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims 2
• JOHCVVJGGSABQY-UHFFFAOYSA-N carbon tetraiodide Chemical compound IC(I)(I)I JOHCVVJGGSABQY-UHFFFAOYSA-N 0.000 claims 2
• RPZYZUCIAZGVRX-UHFFFAOYSA-N 2-(fluoromethyl)-7H-purine Chemical compound FCC1=NC=C2NC=NC2=N1 RPZYZUCIAZGVRX-UHFFFAOYSA-N 0.000 claims 1
• 230000037396 body weight Effects 0.000 claims 1
• 230000007278 cognition impairment Effects 0.000 claims 1
• 230000002526 effect on cardiovascular system Effects 0.000 claims 1
• 239000002253 acid Substances 0.000 description 48
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
• 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 38
• 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 38
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 35
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
• 150000003857 carboxamides Chemical class 0.000 description 35
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 description 27
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 27
• 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 26
• 238000006243 chemical reaction Methods 0.000 description 26
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• 238000012360 testing method Methods 0.000 description 14
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
• 241000700159 Rattus Species 0.000 description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• 229940088598 enzyme Drugs 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 11
• 125000000714 pyrimidinyl group Chemical group 0.000 description 11
• 241000124008 Mammalia Species 0.000 description 10
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 230000002401 inhibitory effect Effects 0.000 description 10
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 8
• 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 8
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 8
• 229960005305 adenosine Drugs 0.000 description 8
• 125000002619 bicyclic group Chemical group 0.000 description 8
• 229940093499 ethyl acetate Drugs 0.000 description 8
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
• 125000003386 piperidinyl group Chemical group 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
• 101100296719 Caenorhabditis elegans pde-4 gene Proteins 0.000 description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 7
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 125000002632 imidazolidinyl group Chemical group 0.000 description 7
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 7
• 230000003834 intracellular effect Effects 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 230000015654 memory Effects 0.000 description 7
• 125000002950 monocyclic group Chemical group 0.000 description 7
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
• 125000001422 pyrrolinyl group Chemical group 0.000 description 7
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 208000010877 cognitive disease Diseases 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
• 239000003880 polar aprotic solvent Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 6
• 229950005741 rolipram Drugs 0.000 description 6
• 208000000044 Amnesia Diseases 0.000 description 5
• 108010044467 Isoenzymes Proteins 0.000 description 5
• UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 5
• 150000005215 alkyl ethers Chemical class 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
• 230000000926 neurological effect Effects 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 239000008188 pellet Substances 0.000 description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 5
• QFMAZXCBTNIYTN-UHFFFAOYSA-N 2-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]phenol Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1O QFMAZXCBTNIYTN-UHFFFAOYSA-N 0.000 description 4
• QVZKIFDPBKDGJA-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 QVZKIFDPBKDGJA-UHFFFAOYSA-N 0.000 description 4
• BJPNWVVDYIDTHK-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]phenol Chemical compound OC1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 BJPNWVVDYIDTHK-UHFFFAOYSA-N 0.000 description 4
• RPLPBDARRYLIAY-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]phenol Chemical compound C1=CC(O)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 RPLPBDARRYLIAY-UHFFFAOYSA-N 0.000 description 4
• 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 4
• FVMMQNJQAFFMGN-UHFFFAOYSA-N 9-(2,3-dimethoxyphenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(OC)=C1OC FVMMQNJQAFFMGN-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 229910004298 SiO 2 Inorganic materials 0.000 description 4
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
• 238000000540 analysis of variance Methods 0.000 description 4
• 230000003110 anti-inflammatory effect Effects 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 229910052791 calcium Inorganic materials 0.000 description 4
• 125000004663 dialkyl amino group Chemical group 0.000 description 4
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 235000013305 food Nutrition 0.000 description 4
• 125000002636 imidazolinyl group Chemical group 0.000 description 4
• 230000007787 long-term memory Effects 0.000 description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
• ITCCIISXKGSABT-UHFFFAOYSA-N methyl 2-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1C(=O)OC ITCCIISXKGSABT-UHFFFAOYSA-N 0.000 description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
• USVURLSKCYVUFD-UHFFFAOYSA-N n-methyl-9-(3-nitrophenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC([N+]([O-])=O)=C1 USVURLSKCYVUFD-UHFFFAOYSA-N 0.000 description 4
• DMLPLLDCYHLRKX-UHFFFAOYSA-N n-methyl-9-[3-(trifluoromethoxy)phenyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(OC(F)(F)F)=C1 DMLPLLDCYHLRKX-UHFFFAOYSA-N 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 208000011580 syndromic disease Diseases 0.000 description 4
• WXIBBDHMCUAWAG-UHFFFAOYSA-N 2-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]phenol Chemical compound OC1=CC=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 WXIBBDHMCUAWAG-UHFFFAOYSA-N 0.000 description 3
• MBTULFIFECUURA-UHFFFAOYSA-N 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound C1=NC(C)=CC(B2OC(C)(C)C(C)(C)O2)=C1 MBTULFIFECUURA-UHFFFAOYSA-N 0.000 description 3
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 3
• RRXWGSKNIDDRMP-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-thiophen-2-ylsulfonylbenzamide Chemical compound C=12N=CN(C=3C=C(C=CC=3)C(=O)NS(=O)(=O)C=3SC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 RRXWGSKNIDDRMP-UHFFFAOYSA-N 0.000 description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
• GRFXWPMEDWAEMH-UHFFFAOYSA-N 6-chloro-2-(trifluoromethyl)-7h-purine Chemical compound FC(F)(F)C1=NC(Cl)=C2NC=NC2=N1 GRFXWPMEDWAEMH-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 241000725303 Human immunodeficiency virus Species 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 208000026139 Memory disease Diseases 0.000 description 3
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000935 antidepressant agent Substances 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 208000010668 atopic eczema Diseases 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical class O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 230000006984 memory degeneration Effects 0.000 description 3
• 208000023060 memory loss Diseases 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• OLMUHYASBQKWQR-UHFFFAOYSA-N n-cyclopropyl-2-(trifluoromethyl)-7h-purin-6-amine Chemical compound C=12NC=NC2=NC(C(F)(F)F)=NC=1NC1CC1 OLMUHYASBQKWQR-UHFFFAOYSA-N 0.000 description 3
• FBHUZRHYRJBFKJ-UHFFFAOYSA-N n-cyclopropyl-9-(3-nitrophenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 FBHUZRHYRJBFKJ-UHFFFAOYSA-N 0.000 description 3
• BBZWZMZVWWYEEV-UHFFFAOYSA-N n-cyclopropyl-9-(3-phenylmethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 BBZWZMZVWWYEEV-UHFFFAOYSA-N 0.000 description 3
• REZNGPBTQSQGQG-UHFFFAOYSA-N n-cyclopropyl-9-[(2-fluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 REZNGPBTQSQGQG-UHFFFAOYSA-N 0.000 description 3
• XCOPCGLQHVDCOT-UHFFFAOYSA-N n-methyl-2-(trifluoromethyl)-7h-purin-6-amine Chemical compound CNC1=NC(C(F)(F)F)=NC2=C1NC=N2 XCOPCGLQHVDCOT-UHFFFAOYSA-N 0.000 description 3
• NPALSBVCCSTITO-UHFFFAOYSA-N n-methyl-9-(2-methylsulfinylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1S(C)=O NPALSBVCCSTITO-UHFFFAOYSA-N 0.000 description 3
• GNXJFUHRHBKSNY-UHFFFAOYSA-N n-methyl-9-(2-phenylmethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1OCC1=CC=CC=C1 GNXJFUHRHBKSNY-UHFFFAOYSA-N 0.000 description 3
• ORWXBLBRENXXHA-UHFFFAOYSA-N n-methyl-9-(3-methylsulfonylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(S(C)(=O)=O)=C1 ORWXBLBRENXXHA-UHFFFAOYSA-N 0.000 description 3
• QLYDCKVYZKNCLQ-UHFFFAOYSA-N n-methyl-9-[2-(trifluoromethoxy)phenyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1OC(F)(F)F QLYDCKVYZKNCLQ-UHFFFAOYSA-N 0.000 description 3
• UHPOOOQTQPYXEN-UHFFFAOYSA-N n-methyl-9-quinolin-8-yl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CN=C2C(N3C=4N=C(N=C(C=4N=C3)NC)C(F)(F)F)=CC=CC2=C1 UHPOOOQTQPYXEN-UHFFFAOYSA-N 0.000 description 3
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 125000003107 substituted aryl group Chemical group 0.000 description 3
• 150000003457 sulfones Chemical class 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 230000002792 vascular Effects 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 230000003936 working memory Effects 0.000 description 3
• UFYBTLOLWSABAU-UHFFFAOYSA-N (2-methylpyridin-4-yl)boronic acid Chemical compound CC1=CC(B(O)O)=CC=N1 UFYBTLOLWSABAU-UHFFFAOYSA-N 0.000 description 2
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
• FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 2
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 2
• GNCLPNMQEGMNTG-UHFFFAOYSA-N 2-methylpyridin-4-amine Chemical compound CC1=CC(N)=CC=N1 GNCLPNMQEGMNTG-UHFFFAOYSA-N 0.000 description 2
• VYOMMURRJYWRSN-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-(2,6-difluorophenyl)sulfonylbenzamide Chemical compound FC1=CC=CC(F)=C1S(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 VYOMMURRJYWRSN-UHFFFAOYSA-N 0.000 description 2
• TWSGUSHLSSFAII-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-(4-fluorophenyl)sulfonylbenzamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 TWSGUSHLSSFAII-UHFFFAOYSA-N 0.000 description 2
• XLDHAVUHBPMPNJ-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-[(6-ethoxy-1,3-benzothiazol-2-yl)sulfonyl]benzamide Chemical compound S1C2=CC(OCC)=CC=C2N=C1S(=O)(=O)NC(=O)C(C=1)=CC=CC=1N(C1=NC(=N2)C(F)(F)F)C=NC1=C2NC1CC1 XLDHAVUHBPMPNJ-UHFFFAOYSA-N 0.000 description 2
• MXMVYAASIMPIEK-UHFFFAOYSA-N 3-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]phenol Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(O)=C1 MXMVYAASIMPIEK-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
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• SZVYTDYZSICKAS-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-ethylsulfonylbenzamide Chemical compound C1=CC(C(=O)NS(=O)(=O)CC)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 SZVYTDYZSICKAS-UHFFFAOYSA-N 0.000 description 2
• JFBMFWHEXBLFCR-UHFFFAOYSA-N 4-bromo-2-methylpyridine Chemical compound CC1=CC(Br)=CC=N1 JFBMFWHEXBLFCR-UHFFFAOYSA-N 0.000 description 2
• YOWCCHJCRYGTHI-UHFFFAOYSA-N 6-chloro-9-[(2-fluorophenyl)methyl]-2-(trifluoromethyl)purine Chemical compound FC1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(Cl)=C2N=C1 YOWCCHJCRYGTHI-UHFFFAOYSA-N 0.000 description 2
• MNNDEJMLXVQHIL-UHFFFAOYSA-N 6-n'-cyclopropyl-2-(trifluoromethyl)purine-6,6-diamine Chemical compound N1=C(C(F)(F)F)N=C2N=CN=C2C1(N)NC1CC1 MNNDEJMLXVQHIL-UHFFFAOYSA-N 0.000 description 2
• VDQLGPMWSILBSR-UHFFFAOYSA-N 9-(2-methoxypyrimidin-4-yl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(OC)=N1 VDQLGPMWSILBSR-UHFFFAOYSA-N 0.000 description 2
• CEFGQJBABYWKTG-UHFFFAOYSA-N 9-(3-aminophenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(N)=C1 CEFGQJBABYWKTG-UHFFFAOYSA-N 0.000 description 2
• KMKGJPAUHYBNIF-UHFFFAOYSA-N 9-(3-iodophenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(I)=C1 KMKGJPAUHYBNIF-UHFFFAOYSA-N 0.000 description 2
• AUQRBGALEBSZLC-UHFFFAOYSA-N 9-cyclopentyl-n-ethyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NCC)=NC(C(F)(F)F)=NC=2N1C1CCCC1 AUQRBGALEBSZLC-UHFFFAOYSA-N 0.000 description 2
• AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 2
• 102000009346 Adenosine receptors Human genes 0.000 description 2
• 108050000203 Adenosine receptors Proteins 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 206010006458 Bronchitis chronic Diseases 0.000 description 2
• 102000000584 Calmodulin Human genes 0.000 description 2
• 108010041952 Calmodulin Proteins 0.000 description 2
• 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
• 206010012438 Dermatitis atopic Diseases 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 2
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 206010063837 Reperfusion injury Diseases 0.000 description 2
• 206010039085 Rhinitis allergic Diseases 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 229950006790 adenosine phosphate Drugs 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 125000005233 alkylalcohol group Chemical group 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 208000002205 allergic conjunctivitis Diseases 0.000 description 2
• 201000010105 allergic rhinitis Diseases 0.000 description 2
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 230000003109 amnesic effect Effects 0.000 description 2
• 230000001430 anti-depressive effect Effects 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 125000005418 aryl aryl group Chemical group 0.000 description 2
• 201000008937 atopic dermatitis Diseases 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 125000000068 chlorophenyl group Chemical group 0.000 description 2
• 125000006378 chloropyridyl group Chemical group 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 239000000544 cholinesterase inhibitor Substances 0.000 description 2
• 208000007451 chronic bronchitis Diseases 0.000 description 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
• 230000006735 deficit Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 125000004212 difluorophenyl group Chemical group 0.000 description 2
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 229960003530 donepezil Drugs 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 125000001207 fluorophenyl group Chemical group 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 231100000863 loss of memory Toxicity 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• WXHMEXHMKGNROM-UHFFFAOYSA-N methyl 3-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(C(=O)OC)=C1 WXHMEXHMKGNROM-UHFFFAOYSA-N 0.000 description 2
• 125000006384 methylpyridyl group Chemical group 0.000 description 2
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 2
• 208000027061 mild cognitive impairment Diseases 0.000 description 2
• 210000002464 muscle smooth vascular Anatomy 0.000 description 2
• PQUNUIADCKLZJA-UHFFFAOYSA-N n-(4-chloropyridin-3-yl)sulfonyl-3-[2-(trifluoromethyl)purin-9-yl]benzamide Chemical compound C12=NC(C(F)(F)F)=NC=C2N=CN1C(C=1)=CC=CC=1C(=O)NS(=O)(=O)C1=CN=CC=C1Cl PQUNUIADCKLZJA-UHFFFAOYSA-N 0.000 description 2
• FLEWACUGPSWNFZ-UHFFFAOYSA-N n-(5-chlorothiophen-2-yl)sulfonyl-3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzamide Chemical compound C=12N=CN(C=3C=C(C=CC=3)C(=O)NS(=O)(=O)C=3SC(Cl)=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 FLEWACUGPSWNFZ-UHFFFAOYSA-N 0.000 description 2
• FLAKFQRCBIJCTR-UHFFFAOYSA-N n-[2-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]phenyl]methanesulfonamide Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1NS(C)(=O)=O FLAKFQRCBIJCTR-UHFFFAOYSA-N 0.000 description 2
• LCGPEQZDVALZDN-UHFFFAOYSA-N n-[3-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]phenyl]methanesulfonamide Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(NS(C)(=O)=O)=C1 LCGPEQZDVALZDN-UHFFFAOYSA-N 0.000 description 2
• RPHIMXRTWFGURB-UHFFFAOYSA-N n-cyclopropyl-9-(2,6-dimethoxypyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=NC(OC)=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=N1 RPHIMXRTWFGURB-UHFFFAOYSA-N 0.000 description 2
• YPXHLRKKPFUCGC-UHFFFAOYSA-N n-cyclopropyl-9-(2-methoxypyridin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC(OC)=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 YPXHLRKKPFUCGC-UHFFFAOYSA-N 0.000 description 2
• SQBNAVJJBVFKDC-UHFFFAOYSA-N n-cyclopropyl-9-(2-methoxypyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=NC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=N1 SQBNAVJJBVFKDC-UHFFFAOYSA-N 0.000 description 2
• ISPYDKIJTULVNV-UHFFFAOYSA-N n-cyclopropyl-9-(2-methylpyridin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC(C)=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 ISPYDKIJTULVNV-UHFFFAOYSA-N 0.000 description 2
• NKVJQLYANHSARO-UHFFFAOYSA-N n-cyclopropyl-9-(2-morpholin-4-ylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3N=C(N=CC=3)N3CCOCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 NKVJQLYANHSARO-UHFFFAOYSA-N 0.000 description 2
• QLNXFZYBKKOXOP-UHFFFAOYSA-N n-cyclopropyl-9-(3-ethylsulfonylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound CCS(=O)(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 QLNXFZYBKKOXOP-UHFFFAOYSA-N 0.000 description 2
• FIJQKRCFKZEEOG-UHFFFAOYSA-N n-cyclopropyl-9-(3-methylpyridin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound CC1=CN=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 FIJQKRCFKZEEOG-UHFFFAOYSA-N 0.000 description 2
• IXGXREDVRBGPFC-UHFFFAOYSA-N n-cyclopropyl-9-(3-methylsulfonylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound CS(=O)(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 IXGXREDVRBGPFC-UHFFFAOYSA-N 0.000 description 2
• YNVYXWAVNOCSJL-UHFFFAOYSA-N n-cyclopropyl-9-(4,6-dimethoxypyrimidin-2-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=CC(OC)=NC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=N1 YNVYXWAVNOCSJL-UHFFFAOYSA-N 0.000 description 2
• FCSSNKZDXWAYIX-UHFFFAOYSA-N n-cyclopropyl-9-[(3-nitrophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound [O-][N+](=O)C1=CC=CC(CN2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 FCSSNKZDXWAYIX-UHFFFAOYSA-N 0.000 description 2
• WZCJAJTVQXPBIM-UHFFFAOYSA-N n-methyl-9-(2-methylsulfonylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(S(C)(=O)=O)=N1 WZCJAJTVQXPBIM-UHFFFAOYSA-N 0.000 description 2
• HZXFTAAVPQCQNL-UHFFFAOYSA-N n-methyl-9-(2-nitrophenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1[N+]([O-])=O HZXFTAAVPQCQNL-UHFFFAOYSA-N 0.000 description 2
• RDYUFYOWVZMIAN-UHFFFAOYSA-N n-methyl-9-(3-methylsulfanylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(SC)=C1 RDYUFYOWVZMIAN-UHFFFAOYSA-N 0.000 description 2
• MMMIMGNMHHUBFY-UHFFFAOYSA-N n-methyl-9-(3-phenylmethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C(C=1)=CC=CC=1OCC1=CC=CC=C1 MMMIMGNMHHUBFY-UHFFFAOYSA-N 0.000 description 2
• 210000000653 nervous system Anatomy 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
• 108010028584 nucleotidase Proteins 0.000 description 2
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000006186 oral dosage form Substances 0.000 description 2
• 239000007800 oxidant agent Substances 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 239000003444 phase transfer catalyst Substances 0.000 description 2
• RRRUXBQSQLKHEL-UHFFFAOYSA-N piclamilast Chemical compound COC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OC1CCCC1 RRRUXBQSQLKHEL-UHFFFAOYSA-N 0.000 description 2
• 229950005184 piclamilast Drugs 0.000 description 2
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
• 150000003462 sulfoxides Chemical class 0.000 description 2
• 230000002194 synthesizing effect Effects 0.000 description 2
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 241000701447 unidentified baculovirus Species 0.000 description 2
• 238000005303 weighing Methods 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• RCVDPBFUMYUKPB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1OC RCVDPBFUMYUKPB-UHFFFAOYSA-N 0.000 description 1
• CJMUIIBZOBKEGZ-UHFFFAOYSA-N (3-methoxypyridin-4-yl)boronic acid Chemical compound COC1=CN=CC=C1B(O)O CJMUIIBZOBKEGZ-UHFFFAOYSA-N 0.000 description 1
• KSERCJHSQPNSJM-UHFFFAOYSA-N (3-methylpyridin-4-yl)boronic acid Chemical compound CC1=CN=CC=C1B(O)O KSERCJHSQPNSJM-UHFFFAOYSA-N 0.000 description 1
• GJRHZPFGAFOKMY-SSDOTTSWSA-N (4r)-4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]pyrrolidin-2-one Chemical compound C=12N=CN([C@@H]3CC(=O)NC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 GJRHZPFGAFOKMY-SSDOTTSWSA-N 0.000 description 1
• GJRHZPFGAFOKMY-ZETCQYMHSA-N (4s)-4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]pyrrolidin-2-one Chemical compound C=12N=CN([C@H]3CC(=O)NC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 GJRHZPFGAFOKMY-ZETCQYMHSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• HJPRDDKCXVCFOH-UHFFFAOYSA-N 1,3-dibutyl-7-(2-oxopropyl)purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC(C)=O)C=N2 HJPRDDKCXVCFOH-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• HYUAYBXVWVDLJV-UHFFFAOYSA-N 1-[3-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]phenyl]ethanone Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(C(C)=O)=C1 HYUAYBXVWVDLJV-UHFFFAOYSA-N 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000006023 1-pentenyl group Chemical group 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
• VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
• SLPBZJPJRTYAPU-UHFFFAOYSA-N 2-(trifluoromethyl)-3,7-dihydropurin-6-one Chemical compound O=C1NC(C(F)(F)F)=NC2=C1N=CN2 SLPBZJPJRTYAPU-UHFFFAOYSA-N 0.000 description 1
• NOORXQVKQJQVNW-UHFFFAOYSA-N 2-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 NOORXQVKQJQVNW-UHFFFAOYSA-N 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• QWFLIRCUHQUGTI-UHFFFAOYSA-N 2-methyl-4-nitro-1-oxidopyridin-1-ium 2-methylpyridin-4-amine Chemical compound [N+](=O)([O-])C=1C=C([N+](=CC1)[O-])C.NC1=CC(=NC=C1)C QWFLIRCUHQUGTI-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 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 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• CZTGVGRZKNHNQQ-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-(2,4-difluorophenyl)sulfonylbenzamide Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 CZTGVGRZKNHNQQ-UHFFFAOYSA-N 0.000 description 1
• MRDYLPNERBVJNW-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-(5-methylpyridin-2-yl)sulfonylbenzamide Chemical compound N1=CC(C)=CC=C1S(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 MRDYLPNERBVJNW-UHFFFAOYSA-N 0.000 description 1
• KJEDLAOJYJUZCK-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-ethylsulfonylbenzamide Chemical compound CCS(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 KJEDLAOJYJUZCK-UHFFFAOYSA-N 0.000 description 1
• CRVPLYPHXZQKII-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-methylsulfonylbenzamide Chemical compound CS(=O)(=O)NC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 CRVPLYPHXZQKII-UHFFFAOYSA-N 0.000 description 1
• RZKPYUQPSIRDFL-UHFFFAOYSA-N 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzonitrile Chemical compound C=12N=CN(C=3C=C(C=CC=3)C#N)C2=NC(C(F)(F)F)=NC=1NC1CC1 RZKPYUQPSIRDFL-UHFFFAOYSA-N 0.000 description 1
• JSFADFFXZGJHTL-UHFFFAOYSA-N 3-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]-n-methylsulfonylbenzamide Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(C(=O)NS(C)(=O)=O)=C1 JSFADFFXZGJHTL-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• HLRJDJZOIOTKSF-UHFFFAOYSA-N 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=CN=CC=C1B1OC(C)(C)C(C)(C)O1 HLRJDJZOIOTKSF-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• NIGDWBHWHVHOAD-UHFFFAOYSA-N 4,6-dichloropyrimidin-5-amine Chemical compound NC1=C(Cl)N=CN=C1Cl NIGDWBHWHVHOAD-UHFFFAOYSA-N 0.000 description 1
• UTUUPXBCDMQYRR-HSZRJFAPSA-N 4-[(2r)-2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl]pyridine Chemical compound COC1=CC=C([C@H](CC=2C=CN=CC=2)C=2C=CC=CC=2)C=C1OC1CCCC1 UTUUPXBCDMQYRR-HSZRJFAPSA-N 0.000 description 1
• ZZHHSKQFFAMZBS-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-(4-fluorophenyl)sulfonylbenzamide;3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F.C1=CC(F)=CC=C1S(=O)(=O)NC(=O)C1=CC=C(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)C=C1 ZZHHSKQFFAMZBS-UHFFFAOYSA-N 0.000 description 1
• CDLKSWAZUAPSEC-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]-n-methylsulfonylbenzamide Chemical compound C1=CC(C(=O)NS(=O)(=O)C)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 CDLKSWAZUAPSEC-UHFFFAOYSA-N 0.000 description 1
• QSQXVRJSGGZOPY-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 QSQXVRJSGGZOPY-UHFFFAOYSA-N 0.000 description 1
• LPCAFJSJYJSOPB-UHFFFAOYSA-N 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoic acid methyl 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound C1(CC1)NC1=C2N=CN(C2=NC(=N1)C(F)(F)F)C1=CC=C(C=C1)C(=O)OC.C(=O)(O)C1=CC=C(C=C1)N1C2=NC(=NC(=C2N=C1)NC1CC1)C(F)(F)F LPCAFJSJYJSOPB-UHFFFAOYSA-N 0.000 description 1
• VUKNJKPTSLLLIJ-UHFFFAOYSA-N 4-[[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]methyl]benzonitrile Chemical compound C=12N=CN(CC=3C=CC(=CC=3)C#N)C2=NC(C(F)(F)F)=NC=1NC1CC1 VUKNJKPTSLLLIJ-UHFFFAOYSA-N 0.000 description 1
• GYUAOSJIGMDMNJ-UHFFFAOYSA-N 4-bromo-3-methylpyridine Chemical compound CC1=CN=CC=C1Br GYUAOSJIGMDMNJ-UHFFFAOYSA-N 0.000 description 1
• DFOHHQRGDOQMKG-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(Cl)=N1 DFOHHQRGDOQMKG-UHFFFAOYSA-N 0.000 description 1
• UPJKSWLLCONYMW-UHFFFAOYSA-N 5'-Adenosine monophosphate Natural products COc1cc(O)c(C(=O)C)c(OC2OC(COC3OC(C)C(O)C(O)C3O)C(O)C(O)C2O)c1 UPJKSWLLCONYMW-UHFFFAOYSA-N 0.000 description 1
• 102100022464 5'-nucleotidase Human genes 0.000 description 1
• TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 1
• RKNWCEIMJJFOKX-UHFFFAOYSA-N 9-(1,3-benzodioxol-5-yl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=C4OCOC4=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 RKNWCEIMJJFOKX-UHFFFAOYSA-N 0.000 description 1
• IYFFZJCWTVNPMM-UHFFFAOYSA-N 9-(1,3-benzodioxol-5-ylmethyl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=C4OCOC4=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 IYFFZJCWTVNPMM-UHFFFAOYSA-N 0.000 description 1
• JDXPAPAFHNGWCK-UHFFFAOYSA-N 9-(2-aminopyrimidin-4-yl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(N)=N1 JDXPAPAFHNGWCK-UHFFFAOYSA-N 0.000 description 1
• ZMMCBJXOCQAOSI-UHFFFAOYSA-N 9-(2-chloropyrimidin-4-yl)-n-ethyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NCC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(Cl)=N1 ZMMCBJXOCQAOSI-UHFFFAOYSA-N 0.000 description 1
• SRIGYBQUPJIVRK-UHFFFAOYSA-N 9-(2-cyclopentylethyl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CCC3CCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 SRIGYBQUPJIVRK-UHFFFAOYSA-N 0.000 description 1
• UZNGUNKFOXNYIW-UHFFFAOYSA-N 9-(2-fluoro-3-methoxyphenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC(OC)=C1F UZNGUNKFOXNYIW-UHFFFAOYSA-N 0.000 description 1
• YUKFCRJOEKNDEX-UHFFFAOYSA-N 9-(2-methoxyphenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=CC=C1OC YUKFCRJOEKNDEX-UHFFFAOYSA-N 0.000 description 1
• ANACSONWUSQSOH-UHFFFAOYSA-N 9-(2-phenylmethoxyphenyl)-2-(trifluoromethyl)purine Chemical class C12=NC(C(F)(F)F)=NC=C2N=CN1C1=CC=CC=C1OCC1=CC=CC=C1 ANACSONWUSQSOH-UHFFFAOYSA-N 0.000 description 1
• ZFOSGOAXYJUXER-UHFFFAOYSA-N 9-(3-chloropyridin-4-yl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C(=CN=CC=3)Cl)C2=NC(C(F)(F)F)=NC=1NC1CC1 ZFOSGOAXYJUXER-UHFFFAOYSA-N 0.000 description 1
• RBFHBWDECNKIRD-UHFFFAOYSA-N 9-(3-methoxyphenyl)-6-methyl-2-(trifluoromethyl)purin-8-amine Chemical compound COC1=CC=CC(N2C3=NC(=NC(C)=C3N=C2N)C(F)(F)F)=C1 RBFHBWDECNKIRD-UHFFFAOYSA-N 0.000 description 1
• PPCBBPWKYDWMSS-UHFFFAOYSA-N 9-(4-methoxyphenyl)-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=C(OC)C=C1 PPCBBPWKYDWMSS-UHFFFAOYSA-N 0.000 description 1
• ZRRYSWSWNIGGOA-UHFFFAOYSA-N 9-(5-chloropyridin-3-yl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=C(Cl)C=NC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 ZRRYSWSWNIGGOA-UHFFFAOYSA-N 0.000 description 1
• SYGBXDDKJMRRJP-UHFFFAOYSA-N 9-(cyclopentylmethyl)-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC3CCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 SYGBXDDKJMRRJP-UHFFFAOYSA-N 0.000 description 1
• MXBXLLNPEJXUCF-UHFFFAOYSA-N 9-[(2-chloro-4-fluorophenyl)methyl]-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound ClC1=CC(F)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 MXBXLLNPEJXUCF-UHFFFAOYSA-N 0.000 description 1
• XSEBRYNRLXTUDP-UHFFFAOYSA-N 9-[(2-chlorophenyl)methyl]-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C(=CC=CC=3)Cl)C2=NC(C(F)(F)F)=NC=1NC1CC1 XSEBRYNRLXTUDP-UHFFFAOYSA-N 0.000 description 1
• QWECFCKUHAMUOT-UHFFFAOYSA-N 9-[(2-fluorophenyl)methyl]-n-methyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1CC1=CC=CC=C1F QWECFCKUHAMUOT-UHFFFAOYSA-N 0.000 description 1
• NGSMCYGYWWUHDL-UHFFFAOYSA-N 9-[(2-fluorophenyl)methyl]-n-propan-2-yl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC(C)C)=NC(C(F)(F)F)=NC=2N1CC1=CC=CC=C1F NGSMCYGYWWUHDL-UHFFFAOYSA-N 0.000 description 1
• AEMVHGKSWPVHFH-UHFFFAOYSA-N 9-[(4-chlorophenyl)methyl]-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=CC(Cl)=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 AEMVHGKSWPVHFH-UHFFFAOYSA-N 0.000 description 1
• HMIOIKJEDCYUFC-UHFFFAOYSA-N 9-[(4-tert-butylphenyl)methyl]-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 HMIOIKJEDCYUFC-UHFFFAOYSA-N 0.000 description 1
• WFTKXVZQSPLNPC-UHFFFAOYSA-N 9-benzyl-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=CC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 WFTKXVZQSPLNPC-UHFFFAOYSA-N 0.000 description 1
• NZJYDIBIFZDPST-UHFFFAOYSA-N 9-butyl-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound N1=C(C(F)(F)F)N=C2N(CCCC)C=NC2=C1NC1CC1 NZJYDIBIFZDPST-UHFFFAOYSA-N 0.000 description 1
• WPWDCOIHEYJFAQ-UHFFFAOYSA-N 9-cycloheptyl-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C3CCCCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 WPWDCOIHEYJFAQ-UHFFFAOYSA-N 0.000 description 1
• KQCSZGQITSJOIE-UHFFFAOYSA-N 9-cyclohexyl-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C3CCCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 KQCSZGQITSJOIE-UHFFFAOYSA-N 0.000 description 1
• LLJBIHPUQXWNRP-UHFFFAOYSA-N 9-cyclopentyl-n-cyclopropyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C3CCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 LLJBIHPUQXWNRP-UHFFFAOYSA-N 0.000 description 1
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
• 208000002874 Acne Vulgaris Diseases 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 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 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 206010051113 Arterial restenosis Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
• 101100135858 Caenorhabditis elegans pde-2 gene Proteins 0.000 description 1
• 101100135867 Caenorhabditis elegans pde-3 gene Proteins 0.000 description 1
• 101100296726 Caenorhabditis elegans pde-5 gene Proteins 0.000 description 1
• 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
• 208000020446 Cardiac disease Diseases 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
• 239000004381 Choline salt Substances 0.000 description 1
• 208000032544 Cicatrix Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 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
• 208000020401 Depressive disease Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 206010016880 Folate deficiency Diseases 0.000 description 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
• 206010017865 Gastritis erosive Diseases 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
• 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 1
• 206010018691 Granuloma Diseases 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 206010018852 Haematoma Diseases 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 101001098805 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4A Proteins 0.000 description 1
• 101000988424 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4B Proteins 0.000 description 1
• 101000988423 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4C Proteins 0.000 description 1
• 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• 206010020649 Hyperkeratosis Diseases 0.000 description 1
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
• 208000031814 IgA Vasculitis Diseases 0.000 description 1
• 206010061216 Infarction Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 208000001126 Keratosis Diseases 0.000 description 1
• 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 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 206010026749 Mania Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027202 Meningitis bacterial Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 201000009053 Neurodermatitis Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
• 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
• 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
• 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
• 206010062519 Poor quality sleep Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 208000003251 Pruritus Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 1
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 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
• 206010042496 Sunburn Diseases 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000024780 Urticaria Diseases 0.000 description 1
• 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
• 229930003779 Vitamin B12 Natural products 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 206010000496 acne Diseases 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 125000005011 alkyl ether group Chemical group 0.000 description 1
• 208000004631 alopecia areata Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 238000006254 arylation reaction Methods 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 208000024998 atopic conjunctivitis Diseases 0.000 description 1
• 230000003416 augmentation Effects 0.000 description 1
• 201000009904 bacterial meningitis Diseases 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• UNXISIRQWPTTSN-UHFFFAOYSA-N boron;2,3-dimethylbutane-2,3-diol Chemical compound [B].[B].CC(C)(O)C(C)(C)O UNXISIRQWPTTSN-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 102100037092 cAMP-specific 3',5'-cyclic phosphodiesterase 4A Human genes 0.000 description 1
• 102100029168 cAMP-specific 3',5'-cyclic phosphodiesterase 4B Human genes 0.000 description 1
• 102100029169 cAMP-specific 3',5'-cyclic phosphodiesterase 4C Human genes 0.000 description 1
• 102100029170 cAMP-specific 3',5'-cyclic phosphodiesterase 4D Human genes 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 230000005792 cardiovascular activity Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004803 chlorobenzyl group Chemical group 0.000 description 1
• 239000002026 chloroform extract Substances 0.000 description 1
• 150000005698 chloropyrimidines Chemical class 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 235000019417 choline salt Nutrition 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 230000003931 cognitive performance Effects 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000002178 crystalline material Substances 0.000 description 1
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
• 125000002946 cyanobenzyl group Chemical group 0.000 description 1
• 229940095074 cyclic amp Drugs 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 210000000172 cytosol Anatomy 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000000593 degrading effect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 229950004687 denbufylline Drugs 0.000 description 1
• 238000009795 derivation Methods 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000003255 drug test Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000002895 emetic Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• LJJVZJSGXHJIPP-UHFFFAOYSA-N ethylpentyl Chemical group [CH2+]CCC[CH]C[CH2-] LJJVZJSGXHJIPP-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000004175 fluorobenzyl group Chemical group 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 230000027119 gastric acid secretion Effects 0.000 description 1
• 239000007897 gelcap Substances 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 229940005494 general anesthetics Drugs 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 150000002315 glycerophosphates Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005241 heteroarylamino group Chemical class 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 208000003906 hydrocephalus Diseases 0.000 description 1
• 229960000443 hydrochloric acid Drugs 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 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
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000000865 liniment Substances 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 238000003760 magnetic stirring Methods 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Chemical class 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 102000006240 membrane receptors Human genes 0.000 description 1
• 210000003071 memory t lymphocyte Anatomy 0.000 description 1
• 230000009681 mesenchymal cell proliferation Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
• DTPWOYNXPUBEPC-UHFFFAOYSA-N methyl 2-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound COC(=O)C1=CC=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 DTPWOYNXPUBEPC-UHFFFAOYSA-N 0.000 description 1
• BXDARZXQWSSUAJ-UHFFFAOYSA-N methyl 3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 BXDARZXQWSSUAJ-UHFFFAOYSA-N 0.000 description 1
• NBOUIDWLNULGNK-UHFFFAOYSA-N methyl 4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 NBOUIDWLNULGNK-UHFFFAOYSA-N 0.000 description 1
• CHKPOXQGJVKVLZ-UHFFFAOYSA-N methyl 4-[6-(methylamino)-2-(trifluoromethyl)purin-9-yl]benzoate Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=C(C(=O)OC)C=C1 CHKPOXQGJVKVLZ-UHFFFAOYSA-N 0.000 description 1
• 125000006178 methyl benzyl group Chemical group 0.000 description 1
• NTPLXRHDUXRPNE-UHFFFAOYSA-N methyl p-methoxyphenyl ketone Natural products COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000001483 mobilizing effect Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• VLLARGUTJGPKPD-UHFFFAOYSA-N n-(3-chlorophenyl)sulfonyl-3-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzamide Chemical compound C=12N=CN(C=3C=C(C=CC=3)C(=O)NS(=O)(=O)C=3C=C(Cl)C=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 VLLARGUTJGPKPD-UHFFFAOYSA-N 0.000 description 1
• KXGYPKYIJFYZAX-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[6-(cyclopropylamino)-2-(trifluoromethyl)purin-9-yl]benzamide Chemical compound C=12N=CN(C=3C=CC(=CC=3)C(=O)NS(=O)(=O)C=3C=CC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 KXGYPKYIJFYZAX-UHFFFAOYSA-N 0.000 description 1
• IPPOJAWZDNNQJQ-UHFFFAOYSA-N n-cyclohexyl-9-[(2-fluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CCCCC3)=C2N=C1 IPPOJAWZDNNQJQ-UHFFFAOYSA-N 0.000 description 1
• YRNPFZZMUSPABG-UHFFFAOYSA-N n-cyclopentyl-9-[(2-fluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CCCC3)=C2N=C1 YRNPFZZMUSPABG-UHFFFAOYSA-N 0.000 description 1
• PYHQVLZNOBYPIA-UHFFFAOYSA-N n-cyclopropyl-2-(trifluoromethyl)-9-[6-(trifluoromethyl)pyridin-3-yl]purin-6-amine Chemical compound C1=NC(C(F)(F)F)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 PYHQVLZNOBYPIA-UHFFFAOYSA-N 0.000 description 1
• UHWNUNPMKIHCTN-UHFFFAOYSA-N n-cyclopropyl-2-(trifluoromethyl)-9-[[3-(trifluoromethyl)phenyl]methyl]purin-6-amine Chemical compound FC(F)(F)C1=CC=CC(CN2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 UHWNUNPMKIHCTN-UHFFFAOYSA-N 0.000 description 1
• DDFVFIKMISUUKQ-UHFFFAOYSA-N n-cyclopropyl-2-(trifluoromethyl)-9-[[4-(trifluoromethyl)phenyl]methyl]purin-6-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 DDFVFIKMISUUKQ-UHFFFAOYSA-N 0.000 description 1
• CPEYHHMCSTVDJU-UHFFFAOYSA-N n-cyclopropyl-9-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=C4OCCOC4=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 CPEYHHMCSTVDJU-UHFFFAOYSA-N 0.000 description 1
• CRPDGPFKQKDZPH-UHFFFAOYSA-N n-cyclopropyl-9-(2-methoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=CC=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 CRPDGPFKQKDZPH-UHFFFAOYSA-N 0.000 description 1
• LLITYJWUFQEXRU-UHFFFAOYSA-N n-cyclopropyl-9-(2-methylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound CC1=NC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=N1 LLITYJWUFQEXRU-UHFFFAOYSA-N 0.000 description 1
• WIOIBLVNYMHCSH-UHFFFAOYSA-N n-cyclopropyl-9-(2-piperidin-1-ylethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CCN3CCCCC3)C2=NC(C(F)(F)F)=NC=1NC1CC1 WIOIBLVNYMHCSH-UHFFFAOYSA-N 0.000 description 1
• OHKXZCGGQZQIHS-UHFFFAOYSA-N n-cyclopropyl-9-(3,4-dimethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=C(OC)C(OC)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 OHKXZCGGQZQIHS-UHFFFAOYSA-N 0.000 description 1
• IBYXGDTZGMKKMH-UHFFFAOYSA-N n-cyclopropyl-9-(3,5-dimethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=CC(OC)=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 IBYXGDTZGMKKMH-UHFFFAOYSA-N 0.000 description 1
• TVGHEELFVQQEGT-UHFFFAOYSA-N n-cyclopropyl-9-(3-ethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound CCOC1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 TVGHEELFVQQEGT-UHFFFAOYSA-N 0.000 description 1
• USFJDMHZYMLQBW-UHFFFAOYSA-N n-cyclopropyl-9-(3-methoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound COC1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 USFJDMHZYMLQBW-UHFFFAOYSA-N 0.000 description 1
• PHOCGBLWEGWKMK-UHFFFAOYSA-N n-cyclopropyl-9-(4-fluorophenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(F)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 PHOCGBLWEGWKMK-UHFFFAOYSA-N 0.000 description 1
• NOJPIVFTNXRWAH-UHFFFAOYSA-N n-cyclopropyl-9-(4-methoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(OC)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 NOJPIVFTNXRWAH-UHFFFAOYSA-N 0.000 description 1
• XCGJLTHUMMRUDS-UHFFFAOYSA-N n-cyclopropyl-9-(4-methylphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(C)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 XCGJLTHUMMRUDS-UHFFFAOYSA-N 0.000 description 1
• DDPUUNZFJSZKOH-UHFFFAOYSA-N n-cyclopropyl-9-(4-phenylmethoxyphenyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 DDPUUNZFJSZKOH-UHFFFAOYSA-N 0.000 description 1
• SRCGWYYAGSHHEH-UHFFFAOYSA-N n-cyclopropyl-9-(furan-3-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC3=COC=C3)C2=NC(C(F)(F)F)=NC=1NC1CC1 SRCGWYYAGSHHEH-UHFFFAOYSA-N 0.000 description 1
• OEIYIOTUKKBRPM-UHFFFAOYSA-N n-cyclopropyl-9-(pyridin-2-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3N=CC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 OEIYIOTUKKBRPM-UHFFFAOYSA-N 0.000 description 1
• CNIZOUFJAGRUPY-UHFFFAOYSA-N n-cyclopropyl-9-(pyridin-4-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=CN=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 CNIZOUFJAGRUPY-UHFFFAOYSA-N 0.000 description 1
• JYZOGEZUHOYAFT-UHFFFAOYSA-N n-cyclopropyl-9-(thiophen-2-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3SC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 JYZOGEZUHOYAFT-UHFFFAOYSA-N 0.000 description 1
• FCBPXPNQDBXORJ-UHFFFAOYSA-N n-cyclopropyl-9-(thiophen-3-ylmethyl)-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC3=CSC=C3)C2=NC(C(F)(F)F)=NC=1NC1CC1 FCBPXPNQDBXORJ-UHFFFAOYSA-N 0.000 description 1
• ZQOKWLPUINQDKS-UHFFFAOYSA-N n-cyclopropyl-9-[(2,3-dichlorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C(=C(Cl)C=CC=3)Cl)C2=NC(C(F)(F)F)=NC=1NC1CC1 ZQOKWLPUINQDKS-UHFFFAOYSA-N 0.000 description 1
• QQTGDFVGYWLYFD-UHFFFAOYSA-N n-cyclopropyl-9-[(2,3-difluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC=CC(CN2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1F QQTGDFVGYWLYFD-UHFFFAOYSA-N 0.000 description 1
• TVBFCMSDDSINBT-UHFFFAOYSA-N n-cyclopropyl-9-[(2,4-dichlorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C(=CC(Cl)=CC=3)Cl)C2=NC(C(F)(F)F)=NC=1NC1CC1 TVBFCMSDDSINBT-UHFFFAOYSA-N 0.000 description 1
• GDKACZRIPUNQSR-UHFFFAOYSA-N n-cyclopropyl-9-[(2,4-difluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC(F)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 GDKACZRIPUNQSR-UHFFFAOYSA-N 0.000 description 1
• QKCCIQWVABSVTI-UHFFFAOYSA-N n-cyclopropyl-9-[(2,6-dichloropyridin-4-yl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=C(Cl)N=C(Cl)C=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 QKCCIQWVABSVTI-UHFFFAOYSA-N 0.000 description 1
• OCKIHYYRWLHELG-UHFFFAOYSA-N n-cyclopropyl-9-[(2,6-difluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC=CC(F)=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 OCKIHYYRWLHELG-UHFFFAOYSA-N 0.000 description 1
• XFOJVGDVZUYXNL-UHFFFAOYSA-N n-cyclopropyl-9-[(2-methylphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound CC1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 XFOJVGDVZUYXNL-UHFFFAOYSA-N 0.000 description 1
• CIBVZVZWXSVNHR-UHFFFAOYSA-N n-cyclopropyl-9-[(2-nitrophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound [O-][N+](=O)C1=CC=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 CIBVZVZWXSVNHR-UHFFFAOYSA-N 0.000 description 1
• PZMCAAYSTIYCLZ-UHFFFAOYSA-N n-cyclopropyl-9-[(2-phenylphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C(=CC=CC=3)C=3C=CC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 PZMCAAYSTIYCLZ-UHFFFAOYSA-N 0.000 description 1
• LUDMYZBDDKCHME-UHFFFAOYSA-N n-cyclopropyl-9-[(3,4-dichlorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=C(Cl)C(Cl)=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 LUDMYZBDDKCHME-UHFFFAOYSA-N 0.000 description 1
• HOGSRMSTKGTPSW-UHFFFAOYSA-N n-cyclopropyl-9-[(3,4-difluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=C(F)C(F)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 HOGSRMSTKGTPSW-UHFFFAOYSA-N 0.000 description 1
• RCBIUVFVVRPENA-UHFFFAOYSA-N n-cyclopropyl-9-[(3,4-dimethoxyphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=C(OC)C(OC)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 RCBIUVFVVRPENA-UHFFFAOYSA-N 0.000 description 1
• YXLKQIUVMZTYOY-UHFFFAOYSA-N n-cyclopropyl-9-[(3,5-difluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC1=CC(F)=CC(CN2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 YXLKQIUVMZTYOY-UHFFFAOYSA-N 0.000 description 1
• RAQSZBUUIYOKSU-UHFFFAOYSA-N n-cyclopropyl-9-[(3-methylphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound CC1=CC=CC(CN2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 RAQSZBUUIYOKSU-UHFFFAOYSA-N 0.000 description 1
• JUAXIASQWZRBEQ-UHFFFAOYSA-N n-cyclopropyl-9-[(3-phenylmethoxyphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(CC=3C=C(OCC=4C=CC=CC=4)C=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 JUAXIASQWZRBEQ-UHFFFAOYSA-N 0.000 description 1
• DQARMIFMNNYOLY-UHFFFAOYSA-N n-cyclopropyl-9-[(4-ethylphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(CC)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 DQARMIFMNNYOLY-UHFFFAOYSA-N 0.000 description 1
• FJKKFFRDWKXBOK-UHFFFAOYSA-N n-cyclopropyl-9-[(4-fluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 FJKKFFRDWKXBOK-UHFFFAOYSA-N 0.000 description 1
• SUYGGIVGHLOLRK-UHFFFAOYSA-N n-cyclopropyl-9-[(4-methoxyphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(OC)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 SUYGGIVGHLOLRK-UHFFFAOYSA-N 0.000 description 1
• DBAPUGOULXHOOA-UHFFFAOYSA-N n-cyclopropyl-9-[(4-nitrophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 DBAPUGOULXHOOA-UHFFFAOYSA-N 0.000 description 1
• RBJYVRYLFPKXLG-UHFFFAOYSA-N n-cyclopropyl-9-[(4-propan-2-ylphenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(C(C)C)=CC=C1CN1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 RBJYVRYLFPKXLG-UHFFFAOYSA-N 0.000 description 1
• JWFDQSVXCORIOH-UHFFFAOYSA-N n-cyclopropyl-9-[3-(trifluoromethoxy)phenyl]-2-(trifluoromethyl)purin-6-amine Chemical compound FC(F)(F)OC1=CC=CC(N2C3=NC(=NC(NC4CC4)=C3N=C2)C(F)(F)F)=C1 JWFDQSVXCORIOH-UHFFFAOYSA-N 0.000 description 1
• OQYPSHQXLUFXAN-UHFFFAOYSA-N n-cyclopropyl-9-[4-(dimethylamino)phenyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=CC(N(C)C)=CC=C1N1C2=NC(C(F)(F)F)=NC(NC3CC3)=C2N=C1 OQYPSHQXLUFXAN-UHFFFAOYSA-N 0.000 description 1
• WANCBESMGPKQJN-UHFFFAOYSA-N n-cyclopropyl-9-ethyl-2-(trifluoromethyl)purin-6-amine Chemical compound N1=C(C(F)(F)F)N=C2N(CC)C=NC2=C1NC1CC1 WANCBESMGPKQJN-UHFFFAOYSA-N 0.000 description 1
• AWKWDDHHEXDEES-UHFFFAOYSA-N n-cyclopropyl-9-phenyl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=CC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 AWKWDDHHEXDEES-UHFFFAOYSA-N 0.000 description 1
• VKXCQVQUQRBBAU-UHFFFAOYSA-N n-cyclopropyl-9-propan-2-yl-2-(trifluoromethyl)purin-6-amine Chemical compound N1=C(C(F)(F)F)N=C2N(C(C)C)C=NC2=C1NC1CC1 VKXCQVQUQRBBAU-UHFFFAOYSA-N 0.000 description 1
• VTMXECZTVKZKCK-UHFFFAOYSA-N n-cyclopropyl-9-pyridin-3-yl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=NC=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 VTMXECZTVKZKCK-UHFFFAOYSA-N 0.000 description 1
• RKPULIUKZOLQCA-UHFFFAOYSA-N n-cyclopropyl-9-pyridin-4-yl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C=3C=CN=CC=3)C2=NC(C(F)(F)F)=NC=1NC1CC1 RKPULIUKZOLQCA-UHFFFAOYSA-N 0.000 description 1
• VPUNYYUMVGYEEH-UHFFFAOYSA-N n-cyclopropyl-9-thiophen-3-yl-2-(trifluoromethyl)purin-6-amine Chemical compound C=12N=CN(C3=CSC=C3)C2=NC(C(F)(F)F)=NC=1NC1CC1 VPUNYYUMVGYEEH-UHFFFAOYSA-N 0.000 description 1
• GIQUWNHXATXJAX-UHFFFAOYSA-N n-ethyl-2-(trifluoromethyl)-7h-purin-6-amine Chemical compound CCNC1=NC(C(F)(F)F)=NC2=C1NC=N2 GIQUWNHXATXJAX-UHFFFAOYSA-N 0.000 description 1
• CWVJMPBKUNRECD-UHFFFAOYSA-N n-ethyl-9-[(2-fluorophenyl)methyl]-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NCC)=NC(C(F)(F)F)=NC=2N1CC1=CC=CC=C1F CWVJMPBKUNRECD-UHFFFAOYSA-N 0.000 description 1
• PPDXTAIQBMVBQG-UHFFFAOYSA-N n-methyl-9-(2-methylsulfanylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(SC)=N1 PPDXTAIQBMVBQG-UHFFFAOYSA-N 0.000 description 1
• JZWMMKBJISBKPY-UHFFFAOYSA-N n-methyl-9-(2-methylsulfinylpyrimidin-4-yl)-2-(trifluoromethyl)purin-6-amine Chemical compound C1=NC=2C(NC)=NC(C(F)(F)F)=NC=2N1C1=CC=NC(S(C)=O)=N1 JZWMMKBJISBKPY-UHFFFAOYSA-N 0.000 description 1
• JGMJZSOMCXGRET-UHFFFAOYSA-N n-methyl-9-[2-(methylamino)pyrimidin-4-yl]-2-(trifluoromethyl)purin-6-amine Chemical compound CNC1=NC=CC(N2C3=NC(=NC(NC)=C3N=C2)C(F)(F)F)=N1 JGMJZSOMCXGRET-UHFFFAOYSA-N 0.000 description 1
• NQTNSBGSMDOIML-UHFFFAOYSA-N n-methyl-9-[3-(methylamino)phenyl]-2-(trifluoromethyl)purin-6-amine Chemical compound CNC1=CC=CC(N2C3=NC(=NC(NC)=C3N=C2)C(F)(F)F)=C1 NQTNSBGSMDOIML-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 230000000626 neurodegenerative effect Effects 0.000 description 1
• 230000004766 neurogenesis Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 150000002814 niacins Chemical class 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000012223 nuclear import Effects 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• GNKZMNRKLCTJAY-UHFFFAOYSA-N p-methylphenyl methyl ketone Natural products CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 1
• 229910052763 palladium Inorganic materials 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
• 229960001476 pentoxifylline Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
• 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 229960004838 phosphoric acid Drugs 0.000 description 1
• 125000005547 pivalate group Chemical group 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 230000009090 positive inotropic effect Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 208000020016 psychiatric disease Diseases 0.000 description 1
• 230000000506 psychotropic effect Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 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
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 239000011369 resultant mixture Substances 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 201000004700 rosacea Diseases 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 231100000241 scar Toxicity 0.000 description 1
• 230000037387 scars Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 208000008742 seborrheic dermatitis Diseases 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 101150114085 soc-2 gene Proteins 0.000 description 1
• 238000009987 spinning Methods 0.000 description 1
• LZCVVMQABORALM-UHFFFAOYSA-N spiro[2.5]octyl Chemical group [CH]1CC11CCCCC1 LZCVVMQABORALM-UHFFFAOYSA-N 0.000 description 1
• LMUMMJCCZMWLEN-UHFFFAOYSA-N spiro[3.3]heptyl Chemical group [CH]1CCC11CCC1 LMUMMJCCZMWLEN-UHFFFAOYSA-N 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 239000001384 succinic acid Chemical class 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• JOKPITBUODAHEN-UHFFFAOYSA-N sulfanylideneplatinum Chemical compound [Pt]=S JOKPITBUODAHEN-UHFFFAOYSA-N 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 229940032330 sulfuric acid Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 150000003567 thiocyanates Chemical class 0.000 description 1
• 125000001806 thionaphthenyl group Chemical group 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 125000005389 trialkylsiloxy group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 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 1
• 102000003390 tumor necrosis factor Human genes 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 201000002327 urinary tract obstruction Diseases 0.000 description 1
• 201000005539 vernal conjunctivitis Diseases 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 235000019163 vitamin B12 Nutrition 0.000 description 1
• 239000011715 vitamin B12 Substances 0.000 description 1
• 208000002670 vitamin B12 deficiency Diseases 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 230000003313 weakening effect Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1