CZ20014163A3 - Deriváty purinu, způsob jejich přípravy a farmaceutické kompozice tyto deriváty obsahující - Google Patents

Info

Publication number

CZ20014163A3

CZ20014163A3 CZ20014163A CZ20014163A CZ20014163A3 CZ 20014163 A3 CZ20014163 A3 CZ 20014163A3 CZ 20014163 A CZ20014163 A CZ 20014163A CZ 20014163 A CZ20014163 A CZ 20014163A CZ 20014163 A3 CZ20014163 A3 CZ 20014163A3

Authority

CZ

Czechia

Prior art keywords

radical

formula

radicals

carbon atoms

phenyl

Prior art date

1999-05-21

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims description 118
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 14
• 230000008569 process Effects 0.000 title claims description 7
• 238000002360 preparation method Methods 0.000 title claims description 6
• 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 6
• 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
• -1 -CH2- heterocyclic Chemical group 0.000 claims abstract description 527
• 150000003839 salts Chemical class 0.000 claims abstract description 47
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
• 239000001257 hydrogen Substances 0.000 claims abstract description 31
• 239000003814 drug Substances 0.000 claims abstract description 23
• 125000003118 aryl group Chemical group 0.000 claims abstract description 22
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
• 239000001301 oxygen Substances 0.000 claims abstract description 11
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
• 150000002367 halogens Chemical group 0.000 claims abstract description 7
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
• 229940079593 drug Drugs 0.000 claims abstract description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 179
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 143
• 150000003254 radicals Chemical class 0.000 claims description 134
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 120
• 125000004432 carbon atom Chemical group C* 0.000 claims description 108
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 84
• 238000006243 chemical reaction Methods 0.000 claims description 68
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 59
• 150000001875 compounds Chemical class 0.000 claims description 43
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
• 239000002253 acid Substances 0.000 claims description 33
• 150000002148 esters Chemical class 0.000 claims description 32
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 30
• 239000011707 mineral Substances 0.000 claims description 30
• 125000000524 functional group Chemical group 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 23
• 229920006395 saturated elastomer Polymers 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 150000007524 organic acids Chemical class 0.000 claims description 17
• 125000006239 protecting group Chemical group 0.000 claims description 17
• 150000005840 aryl radicals Chemical class 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
• 150000007530 organic bases Chemical class 0.000 claims description 16
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
• 150000007522 mineralic acids Chemical class 0.000 claims description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 235000005985 organic acids Nutrition 0.000 claims description 13
• WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 11
• 125000004429 atom Chemical group 0.000 claims description 11
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• 125000004434 sulfur atom Chemical group 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 7
• 125000003158 alcohol group Chemical group 0.000 claims description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• BQOWUDKEXDCGQS-UHFFFAOYSA-N [CH]1CCCC1 Chemical compound [CH]1CCCC1 BQOWUDKEXDCGQS-UHFFFAOYSA-N 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 244000005700 microbiome Species 0.000 claims description 6
• 238000007254 oxidation reaction Methods 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• 241000233866 Fungi Species 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 150000002576 ketones Chemical group 0.000 claims description 5
• 230000009223 neuronal apoptosis Effects 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 238000006722 reduction reaction Methods 0.000 claims description 5
• 239000011593 sulfur Chemical group 0.000 claims description 5
• CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• FIULGFJIHJJXMT-UHFFFAOYSA-N [C]1[N]C=CC=C1 Chemical compound [C]1[N]C=CC=C1 FIULGFJIHJJXMT-UHFFFAOYSA-N 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 230000002927 anti-mitotic effect Effects 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 238000002512 chemotherapy Methods 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 150000003462 sulfoxides Chemical class 0.000 claims description 4
• PNDPNCSMYVPNAC-UFLMWKHXSA-N Cl.Cl.C1C[C@@H](N)CC[C@@H]1NC1=NC(NC=2C=CC(CC#N)=CC=2)=C(N=CN2C3CCCC3)C2=N1 Chemical compound Cl.Cl.C1C[C@@H](N)CC[C@@H]1NC1=NC(NC=2C=CC(CC#N)=CC=2)=C(N=CN2C3CCCC3)C2=N1 PNDPNCSMYVPNAC-UFLMWKHXSA-N 0.000 claims description 3
• WIVQGHIWCTZDGQ-GVVKCMBXSA-N Cl.Cl.CCC(CC)n1cnc2c(Nc3ccc(OC(F)(F)F)cc3)nc(N[C@H]3CC[C@H](N)CC3)nc12 Chemical compound Cl.Cl.CCC(CC)n1cnc2c(Nc3ccc(OC(F)(F)F)cc3)nc(N[C@H]3CC[C@H](N)CC3)nc12 WIVQGHIWCTZDGQ-GVVKCMBXSA-N 0.000 claims description 3
• FPYRELIZACSYJN-KWQHRWRSSA-N Cl.Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(NCCNCc2ccc(Cl)cc2)c2ncn(C3CCCC3)c2n1 Chemical compound Cl.Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(NCCNCc2ccc(Cl)cc2)c2ncn(C3CCCC3)c2n1 FPYRELIZACSYJN-KWQHRWRSSA-N 0.000 claims description 3
• 208000030852 Parasitic disease Diseases 0.000 claims description 3
• 150000001299 aldehydes Chemical class 0.000 claims description 3
• 229910021529 ammonia Inorganic materials 0.000 claims description 3
• 230000002555 anti-neurodegenerative effect Effects 0.000 claims description 3
• KLQNJBAFEFFWQZ-UHFFFAOYSA-N benzoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C1=CC=CC=C1 KLQNJBAFEFFWQZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 238000003379 elimination reaction Methods 0.000 claims description 3
• 238000005886 esterification reaction Methods 0.000 claims description 3
• 230000004770 neurodegeneration Effects 0.000 claims description 3
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
• 150000002923 oximes Chemical group 0.000 claims description 3
• 238000007127 saponification reaction Methods 0.000 claims description 3
• 150000003457 sulfones Chemical class 0.000 claims description 3
• LKMOGYXCKJCDQJ-GJFNAKTISA-N Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)C#N)c2ncn(C3CCCC3)c2n1 Chemical compound Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)C#N)c2ncn(C3CCCC3)c2n1 LKMOGYXCKJCDQJ-GJFNAKTISA-N 0.000 claims description 2
• PJCXALXYKSPAJD-IYARVYRRSA-N N[C@H]1CC[C@@H](CC1)Nc1nc(NCCNCc2ccc(Cl)c(c2)C(F)(F)F)c2ncn(C3CCCC3)c2n1 Chemical compound N[C@H]1CC[C@@H](CC1)Nc1nc(NCCNCc2ccc(Cl)c(c2)C(F)(F)F)c2ncn(C3CCCC3)c2n1 PJCXALXYKSPAJD-IYARVYRRSA-N 0.000 claims description 2
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
• 239000003638 chemical reducing agent Substances 0.000 claims description 2
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
• 239000012948 isocyanate Substances 0.000 claims description 2
• 150000002513 isocyanates Chemical class 0.000 claims description 2
• 150000002823 nitrates Chemical class 0.000 claims description 2
• NHRJSUXFBHVDJS-FGQYVNHASA-N Cl.Cl.Cl.NCCNc1nc(N[C@H]2CC[C@H](N)CC2)nc2n(cnc12)C1CCCC1 Chemical compound Cl.Cl.Cl.NCCNc1nc(N[C@H]2CC[C@H](N)CC2)nc2n(cnc12)C1CCCC1 NHRJSUXFBHVDJS-FGQYVNHASA-N 0.000 claims 1
• 201000007201 aphasia Diseases 0.000 claims 1
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
• 125000001422 pyrrolinyl group Chemical group 0.000 claims 1
• 239000002002 slurry Substances 0.000 claims 1
• 125000000565 sulfonamide group Chemical group 0.000 claims 1
• 125000004001 thioalkyl group Chemical group 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 abstract description 5
• 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 abstract description 2
• 150000002431 hydrogen Chemical group 0.000 abstract 6
• 239000005864 Sulphur Substances 0.000 abstract 2
• 101100294106 Caenorhabditis elegans nhr-3 gene Chemical group 0.000 abstract 1
• 239000000047 product Substances 0.000 description 553
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 410
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 380
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 294
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 247
• 239000012429 reaction media Substances 0.000 description 208
• 238000001035 drying Methods 0.000 description 189
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 172
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 148
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 145
• 239000000243 solution Substances 0.000 description 126
• 239000000377 silicon dioxide Substances 0.000 description 122
• 238000001704 evaporation Methods 0.000 description 117
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 110
• 230000008020 evaporation Effects 0.000 description 104
• VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 94
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 91
• 239000000908 ammonium hydroxide Substances 0.000 description 91
• 238000000926 separation method Methods 0.000 description 90
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
• 239000013078 crystal Substances 0.000 description 88
• 238000004587 chromatography analysis Methods 0.000 description 78
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 74
• 239000002904 solvent Substances 0.000 description 74
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 72
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 64
• 238000000746 purification Methods 0.000 description 60
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 56
• 238000000605 extraction Methods 0.000 description 52
• 230000002829 reductive effect Effects 0.000 description 52
• 239000012895 dilution Substances 0.000 description 42
• 238000010790 dilution Methods 0.000 description 42
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• 239000011780 sodium chloride Substances 0.000 description 30
• 238000001914 filtration Methods 0.000 description 24
• 239000000203 mixture Substances 0.000 description 23
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 20
• 238000002425 crystallisation Methods 0.000 description 20
• 230000008025 crystallization Effects 0.000 description 20
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 17
• 235000010755 mineral Nutrition 0.000 description 17
• 238000003756 stirring Methods 0.000 description 17
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 16
• BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 13
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
• 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 10
• 238000005406 washing Methods 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
• GIZCKBSSWNIUMZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(CN)C=C1 GIZCKBSSWNIUMZ-UHFFFAOYSA-N 0.000 description 8
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 229940093915 gynecological organic acid Drugs 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 238000007796 conventional method Methods 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
• IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 5
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• 238000006482 condensation reaction Methods 0.000 description 5
• 238000010828 elution Methods 0.000 description 5
• 238000002329 infrared spectrum Methods 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 229940098779 methanesulfonic acid Drugs 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 150000003212 purines Chemical class 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• LQLOGZQVKUNBRX-UHFFFAOYSA-N (3-iodophenyl)methanamine Chemical compound NCC1=CC=CC(I)=C1 LQLOGZQVKUNBRX-UHFFFAOYSA-N 0.000 description 4
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
• ZPFSQNUOEIAPRQ-PVPJKCDMSA-N Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)N2CCOCC2)c2ncn(C3CCCC3)c2n1 Chemical compound Cl.Cl.N[C@H]1CC[C@@H](CC1)Nc1nc(Nc2ccc(cc2)N2CCOCC2)c2ncn(C3CCCC3)c2n1 ZPFSQNUOEIAPRQ-PVPJKCDMSA-N 0.000 description 4
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
• 241000196324 Embryophyta Species 0.000 description 4
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
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