DK149892B - Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf - Google Patents

Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf Download PDF

Info

Publication number: DK149892B
Authority: DK; Denmark
Prior art keywords: group; alk; het; ring; compound
Prior art date: 1980-01-07

Application number

DK003281AA

Other languages

Danish (da)

English (en)

Other versions

DK3281A (da

Inventor

Mikkel Josef Gacek

Kjell Undheim

Original Assignee

Nyegaard & Co As

Priority date (The priority date 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 date listed.)

1980-01-07

Filing date

1981-01-06

Publication date

1986-10-20

1981-01-06 Application filed by Nyegaard & Co As filed Critical Nyegaard & Co As

1981-07-08 Publication of DK3281A publication Critical patent/DK3281A/da

1986-10-20 Publication of DK149892B publication Critical patent/DK149892B/da

Links

150000003839 salts Chemical class 0.000 title claims abstract description 20
238000000034 method Methods 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 58
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
125000005843 halogen group Chemical group 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 7
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
125000001424 substituent group Chemical group 0.000 claims abstract description 6
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
229920006395 saturated elastomer Polymers 0.000 claims abstract 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract 2
125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
229910052760 oxygen Inorganic materials 0.000 claims abstract 2
229910052717 sulfur Inorganic materials 0.000 claims abstract 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 20
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 19
230000002378 acidificating effect Effects 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical group C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
125000003158 alcohol group Chemical group 0.000 claims 1
125000005236 alkanoylamino group Chemical group 0.000 claims 1
238000007363 ring formation reaction Methods 0.000 claims 1
230000002159 abnormal effect Effects 0.000 abstract description 15
230000031864 metaphase Effects 0.000 abstract description 9
230000004663 cell proliferation Effects 0.000 abstract description 6
238000006798 ring closing metathesis reaction Methods 0.000 abstract description 5
125000002837 carbocyclic group Chemical group 0.000 abstract description 3
230000022131 cell cycle Effects 0.000 abstract description 3
125000000714 pyrimidinyl group Chemical group 0.000 abstract description 3
229940127089 cytotoxic agent Drugs 0.000 abstract description 2
239000002254 cytotoxic agent Substances 0.000 abstract description 2
125000004442 acylamino group Chemical group 0.000 abstract 1
230000029936 alkylation Effects 0.000 abstract 1
238000005804 alkylation reaction Methods 0.000 abstract 1
230000026030 halogenation Effects 0.000 abstract 1
238000005658 halogenation reaction Methods 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 128
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
239000007787 solid Substances 0.000 description 56
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
235000019439 ethyl acetate Nutrition 0.000 description 42
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 29
239000000203 mixture Substances 0.000 description 27
239000013078 crystal Substances 0.000 description 26
210000004027 cell Anatomy 0.000 description 25
239000000725 suspension Substances 0.000 description 25
239000000243 solution Substances 0.000 description 24
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 23
OCSYCDVQABSEPJ-UHFFFAOYSA-N 5-chloro-1h-pyrimidin-2-one Chemical compound OC1=NC=C(Cl)C=N1 OCSYCDVQABSEPJ-UHFFFAOYSA-N 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 20
239000012071 phase Substances 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
239000003814 drug Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 11
-1 methyl Chemical compound 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 10
239000006260 foam Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000006071 cream Substances 0.000 description 8
239000003208 petroleum Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
230000018199 S phase Effects 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
230000011278 mitosis Effects 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 5
239000012267 brine Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
230000032823 cell division Effects 0.000 description 5
238000011161 development Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
230000006820 DNA synthesis Effects 0.000 description 4
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 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000002585 base Substances 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
231100000433 cytotoxic Toxicity 0.000 description 4
230000001472 cytotoxic effect Effects 0.000 description 4
238000010828 elution Methods 0.000 description 4
KBAODSJOEVGXBY-UHFFFAOYSA-N ethyl 4-(bromomethyl)-2-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1CBr KBAODSJOEVGXBY-UHFFFAOYSA-N 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 4
FUOHKPSBGLXIRL-UHFFFAOYSA-N 2-(chloromethyl)thiophene Chemical compound ClCC1=CC=CS1 FUOHKPSBGLXIRL-UHFFFAOYSA-N 0.000 description 3
GRLWQORZOWPFCM-UHFFFAOYSA-N 5-chloro-1h-pyrimidin-2-one;hydrochloride Chemical compound Cl.ClC=1C=NC(=O)NC=1 GRLWQORZOWPFCM-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
241000400611 Eucalyptus deanei Species 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
BLBVWRXRVAAJCG-UHFFFAOYSA-N ethyl 2-(bromomethyl)-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(CBr)=NC=1C BLBVWRXRVAAJCG-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
230000000394 mitotic effect Effects 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000012360 testing method Methods 0.000 description 3
229930192474 thiophene Natural products 0.000 description 3
238000001665 trituration Methods 0.000 description 3
UAQJEIWAMCLVTE-UHFFFAOYSA-N (3-methylthiophen-2-yl)methanol Chemical compound CC=1C=CSC=1CO UAQJEIWAMCLVTE-UHFFFAOYSA-N 0.000 description 2
DBRSLMCLMMFHEF-UHFFFAOYSA-N (5-bromothiophen-2-yl)methanol Chemical compound OCC1=CC=C(Br)S1 DBRSLMCLMMFHEF-UHFFFAOYSA-N 0.000 description 2
YFUJJGBBAUDCDX-UHFFFAOYSA-N 1-(3-bromo-2-hydroxypropyl)-5-chloropyrimidin-2-one Chemical compound BrCC(O)CN1C=C(Cl)C=NC1=O YFUJJGBBAUDCDX-UHFFFAOYSA-N 0.000 description 2
KMJUNPBVHKPUPN-UHFFFAOYSA-N 1-[(5-bromothiophen-2-yl)methyl]-5-chloropyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CC=C(Br)S1 KMJUNPBVHKPUPN-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
VDQDBLVLPNTJSS-UHFFFAOYSA-N 4-(chloromethyl)-n-trityl-1,3-thiazol-2-amine Chemical compound ClCC1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 VDQDBLVLPNTJSS-UHFFFAOYSA-N 0.000 description 2
MXDXAOQUIXLTBW-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1.CC1=CC=C(S(O)(=O)=O)C=C1 MXDXAOQUIXLTBW-UHFFFAOYSA-N 0.000 description 2
NDCXNAAPTYFDOM-UHFFFAOYSA-N 5-chloro-1-(2-thiophen-2-ylethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CCC1=CC=CS1 NDCXNAAPTYFDOM-UHFFFAOYSA-N 0.000 description 2
JJORBTDLCYWNSG-UHFFFAOYSA-N 5-chloro-1-(oxiran-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1OC1 JJORBTDLCYWNSG-UHFFFAOYSA-N 0.000 description 2
YZOKITXZQWCTGN-UHFFFAOYSA-N 5-chloro-1-[(3-methylthiophen-2-yl)methyl]pyrimidin-2-one Chemical compound C1=CSC(CN2C(N=CC(Cl)=C2)=O)=C1C YZOKITXZQWCTGN-UHFFFAOYSA-N 0.000 description 2
HLXKPNAHHFWHON-UHFFFAOYSA-N 5-chloro-4-hydrazinyl-6-methyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C(NN)=NC(=O)N1CC1=CC=CS1 HLXKPNAHHFWHON-UHFFFAOYSA-N 0.000 description 2
SFWCFDOIDFKHKC-UHFFFAOYSA-N 5-chloro-6-methyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C=NC(=O)N1CC1=CC=CS1 SFWCFDOIDFKHKC-UHFFFAOYSA-N 0.000 description 2
PTXQXRKOPZRLGT-UHFFFAOYSA-N 5-chloro-6-methyl-4-methylsulfanyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C(SC)=NC(=O)N1CC1=CC=CS1 PTXQXRKOPZRLGT-UHFFFAOYSA-N 0.000 description 2
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
239000004342 Benzoyl peroxide Substances 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
230000010337 G2 phase Effects 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 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
206010028980 Neoplasm Diseases 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
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 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
230000000340 anti-metabolite Effects 0.000 description 2
229940100197 antimetabolite Drugs 0.000 description 2
239000002256 antimetabolite Substances 0.000 description 2
235000019400 benzoyl peroxide Nutrition 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000001816 cooling Methods 0.000 description 2
BXOIIRQIGYJTTB-UHFFFAOYSA-N ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1C BXOIIRQIGYJTTB-UHFFFAOYSA-N 0.000 description 2
SFFBELXPCFGXAY-UHFFFAOYSA-N ethyl 2-[(5-chloro-2-oxopyrimidin-1-yl)methyl]-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OCC)SC(CN2C(N=CC(Cl)=C2)=O)=N1 SFFBELXPCFGXAY-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
229960001330 hydroxycarbamide Drugs 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000047 product Substances 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
QIEQDFYXVYQLLU-UHFFFAOYSA-N pyrimidin-4-ylhydrazine Chemical compound NNC1=CC=NC=N1 QIEQDFYXVYQLLU-UHFFFAOYSA-N 0.000 description 2
229910001923 silver oxide Inorganic materials 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
230000001360 synchronised effect Effects 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
BHGUSWOZYFZTMG-UHFFFAOYSA-N (1-methylpyrrol-2-yl)methanol Chemical compound CN1C=CC=C1CO BHGUSWOZYFZTMG-UHFFFAOYSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
VOZFDEJGHQWZHU-UHFFFAOYSA-N (5-methylfuran-2-yl)methanol Chemical compound CC1=CC=C(CO)O1 VOZFDEJGHQWZHU-UHFFFAOYSA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
RCNHNMBERMTYGW-UHFFFAOYSA-N 1-(1-benzothiophen-3-ylmethyl)-5-chloropyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CSC2=CC=CC=C12 RCNHNMBERMTYGW-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
QZOBOLDDGXPTBP-UHFFFAOYSA-N 2-(bromomethyl)thiophene Chemical compound BrCC1=CC=CS1 QZOBOLDDGXPTBP-UHFFFAOYSA-N 0.000 description 1
JHDSVVPTMIYVGV-UHFFFAOYSA-N 2-(chloromethyl)-1-benzothiophene Chemical compound C1=CC=C2SC(CCl)=CC2=C1 JHDSVVPTMIYVGV-UHFFFAOYSA-N 0.000 description 1
XRWMHJJHPQTTLQ-UHFFFAOYSA-N 2-(chloromethyl)thiirane Chemical compound ClCC1CS1 XRWMHJJHPQTTLQ-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
VZWOXDYRBDIHMA-UHFFFAOYSA-N 2-methyl-1,3-thiazole Chemical compound CC1=NC=CS1 VZWOXDYRBDIHMA-UHFFFAOYSA-N 0.000 description 1
VMJOFTHFJMLIKL-UHFFFAOYSA-N 2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1 VMJOFTHFJMLIKL-UHFFFAOYSA-N 0.000 description 1
KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
BSQKBHXYEKVKMN-UHFFFAOYSA-N 3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=CSC=1C=O BSQKBHXYEKVKMN-UHFFFAOYSA-N 0.000 description 1
MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 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
NMAKJOWVEDTHOA-UHFFFAOYSA-N 4-(chloromethyl)-1,3-thiazol-2-amine;hydron;chloride Chemical compound Cl.NC1=NC(CCl)=CS1 NMAKJOWVEDTHOA-UHFFFAOYSA-N 0.000 description 1
NIFAUKBQIAURIM-UHFFFAOYSA-N 4-(chloromethyl)-3,5-dimethyl-1,2-oxazole Chemical compound CC1=NOC(C)=C1CCl NIFAUKBQIAURIM-UHFFFAOYSA-N 0.000 description 1
PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 description 1
FYYLSCWWCHQDFX-UHFFFAOYSA-N 4-thiophen-2-ylbutan-1-ol Chemical compound OCCCCC1=CC=CS1 FYYLSCWWCHQDFX-UHFFFAOYSA-N 0.000 description 1
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
QNFOTGKAEBDUPX-UHFFFAOYSA-N 5-bromo-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Br)C=NC(=O)N1CC1=CC=CS1 QNFOTGKAEBDUPX-UHFFFAOYSA-N 0.000 description 1
VTUDATOSQGYWML-UHFFFAOYSA-N 5-bromo-1h-pyrimidin-2-one Chemical compound OC1=NC=C(Br)C=N1 VTUDATOSQGYWML-UHFFFAOYSA-N 0.000 description 1
GFBVUFQNHLUCPX-UHFFFAOYSA-N 5-bromothiophene-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)S1 GFBVUFQNHLUCPX-UHFFFAOYSA-N 0.000 description 1
APCVAMOUCCXCFN-UHFFFAOYSA-N 5-chloro-1-(3-thiophen-2-ylprop-2-enyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC=CC1=CC=CS1 APCVAMOUCCXCFN-UHFFFAOYSA-N 0.000 description 1
WLHNELCFJBMRSO-UHFFFAOYSA-N 5-chloro-1-(4-thiophen-2-ylbutyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CCCCC1=CC=CS1 WLHNELCFJBMRSO-UHFFFAOYSA-N 0.000 description 1
GRIDMINJJHUQBM-UHFFFAOYSA-N 5-chloro-1-(furan-3-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=COC=C1 GRIDMINJJHUQBM-UHFFFAOYSA-N 0.000 description 1
MHNQAWJKUIZGHT-UHFFFAOYSA-N 5-chloro-1-(pyridin-3-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CC=CN=C1 MHNQAWJKUIZGHT-UHFFFAOYSA-N 0.000 description 1
OBGFTKPMUYHRQZ-UHFFFAOYSA-N 5-chloro-1-(pyridin-4-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CC=NC=C1 OBGFTKPMUYHRQZ-UHFFFAOYSA-N 0.000 description 1
XPWPSXHGRIWZPO-UHFFFAOYSA-N 5-chloro-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CC=CS1 XPWPSXHGRIWZPO-UHFFFAOYSA-N 0.000 description 1
XEWJNYQNOYEQIC-UHFFFAOYSA-N 5-chloro-1-(thiophen-3-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CSC=C1 XEWJNYQNOYEQIC-UHFFFAOYSA-N 0.000 description 1
FCPCSBRNZOQTJH-UHFFFAOYSA-N 5-chloro-1-[(1-methylpyrrol-2-yl)methyl]pyrimidin-2-one Chemical compound CN1C=CC=C1CN1C(=O)N=CC(Cl)=C1 FCPCSBRNZOQTJH-UHFFFAOYSA-N 0.000 description 1
SQEBZDDEYRIBOD-UHFFFAOYSA-N 5-chloro-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]pyrimidin-2-one Chemical compound CC1=NOC(C)=C1CN1C(=O)N=CC(Cl)=C1 SQEBZDDEYRIBOD-UHFFFAOYSA-N 0.000 description 1
PDLBDDVSGLXVTE-UHFFFAOYSA-N 5-chloro-1-[(5-methylfuran-2-yl)methyl]pyrimidin-2-one Chemical compound O1C(C)=CC=C1CN1C(=O)N=CC(Cl)=C1 PDLBDDVSGLXVTE-UHFFFAOYSA-N 0.000 description 1
RJIUYCGKSDTSIT-UHFFFAOYSA-N 5-chloro-1-[[2-(tritylamino)-1,3-thiazol-4-yl]methyl]pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 RJIUYCGKSDTSIT-UHFFFAOYSA-N 0.000 description 1
GUJCXTLRTCFHCN-UHFFFAOYSA-N 5-chloro-6-methyl-4-methylsulfanyl-1h-pyrimidin-2-one Chemical compound CSC1=NC(=O)NC(C)=C1Cl GUJCXTLRTCFHCN-UHFFFAOYSA-N 0.000 description 1
TXKYRAZAKMNKBA-UHFFFAOYSA-N 5-fluoro-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(F)C=NC(=O)N1CC1=CC=CS1 TXKYRAZAKMNKBA-UHFFFAOYSA-N 0.000 description 1
HPABFFGQPLJKBP-UHFFFAOYSA-N 5-fluoro-1H-pyrimidin-2-one Chemical compound OC1=NC=C(F)C=N1 HPABFFGQPLJKBP-UHFFFAOYSA-N 0.000 description 1
HPHMDDGVXBDOLU-UHFFFAOYSA-N 5-iodo-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(I)C=NC(=O)N1CC1=CC=CS1 HPHMDDGVXBDOLU-UHFFFAOYSA-N 0.000 description 1
PVHCYDBPRLPQMP-UHFFFAOYSA-N 5-iodo-1h-pyrimidin-2-one Chemical compound OC1=NC=C(I)C=N1 PVHCYDBPRLPQMP-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
230000027311 M phase Effects 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
125000004036 acetal group Chemical group 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000007824 aliphatic compounds Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
230000031016 anaphase Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000007423 decrease Effects 0.000 description 1
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000009982 effect on human Effects 0.000 description 1
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
125000005677 ethinylene group Chemical class [*:2]C#C[*:1] 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
FRIQFMISUZBMQA-UHFFFAOYSA-N ethyl 4-[(5-chloro-2-oxopyrimidin-1-yl)methyl]-2-methyl-1,3-thiazole-5-carboxylate Chemical compound S1C(C)=NC(CN2C(N=CC(Cl)=C2)=O)=C1C(=O)OCC FRIQFMISUZBMQA-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000003147 glycosyl group Chemical group 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
230000028993 immune response Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
210000005229 liver cell Anatomy 0.000 description 1
239000006210 lotion Substances 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
230000002264 mitodepressive effect Effects 0.000 description 1
230000035773 mitosis phase Effects 0.000 description 1
238000004264 monolayer culture Methods 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
NBUKMHXINQOFDI-UHFFFAOYSA-N n-[4-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CCl)=CS1 NBUKMHXINQOFDI-UHFFFAOYSA-N 0.000 description 1
GDYLSBQKTHPMHJ-UHFFFAOYSA-N n-[4-[(5-chloro-2-oxopyrimidin-1-yl)methyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CN2C(N=CC(Cl)=C2)=O)=C1 GDYLSBQKTHPMHJ-UHFFFAOYSA-N 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
230000009701 normal cell proliferation Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000031877 prophase Effects 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
KEAYESYHFKHZAL-BJUDXGSMSA-N sodium-22 Chemical compound [22Na] KEAYESYHFKHZAL-BJUDXGSMSA-N 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
230000016853 telophase Effects 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
125000002053 thietanyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000014616 translation Effects 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
239000011345 viscous material Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)

DK003281AA 1980-01-07 1981-01-06 Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf DK149892B (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8000381		1980-01-07
GB8000381		1980-01-07

Publications (2)

Publication Number	Publication Date
DK3281A DK3281A (da)	1981-07-08
DK149892B true DK149892B (da)	1986-10-20

Family

ID=10510470

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK003281AA DK149892B (da)	1980-01-07	1981-01-06	Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf

Country Status (13)

Country	Link
US (1)	US4399140A (de)
EP (1)	EP0032131B1 (de)
JP (1)	JPS56150087A (de)
AT (1)	ATE4715T1 (de)
AU (1)	AU543939B2 (de)
CA (1)	CA1168239A (de)
DE (1)	DE3160886D1 (de)
DK (1)	DK149892B (de)
ES (2)	ES498337A0 (de)
IE (1)	IE50765B1 (de)
NO (1)	NO810024L (de)
NZ (1)	NZ195947A (de)
ZA (1)	ZA8164B (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1160226A (en) *	1980-07-15	1984-01-10	Gordon H. Phillipps	Substituted pyrimidin-2-ones, the salts thereof, processes for their preparation, pharmaceutical compositions containing them and a method therefor
NZ197715A (en) *	1980-07-15	1984-12-14	Glaxo Group Ltd	Substituted pyrimin-2-ones and pharmaceutical compositions
US4596870A (en) *	1981-01-09	1986-06-24	Nyegaard & Co. A.S.	Substituted pyrimidin-2-ones and the salts thereof
EP0087326B1 (de) *	1982-02-24	1987-05-13	Nycomed As	Substituierte Pyrimidin-2-one und deren Salze
SU1235864A1 (ru) *	1983-03-11	1986-06-07	Отделение ордена Ленина института химической физики АН СССР	Нитроксильные производные 5-фторурацила,обладающие противоопухолевой активностью
CN103130732A (zh) *	2011-11-22	2013-06-05	上海博康精细化工有限公司	3,5-二甲基-4-氯甲基异噁唑的制备方法
US20160002204A1 (en) *	2014-07-03	2016-01-07	Board Of Regents, The University Of Texas System	Gls1 inhibitors for treating disease
PL3164394T3 (pl)	2014-07-03	2020-09-07	Board Of Regents, The University Of Texas System	Inhibitory GLS1 do leczenia chorób
CN107921044B (zh)	2015-06-30	2022-01-21	德州大学系统董事会	用于治疗疾病的gls1抑制剂
KR102777513B1 (ko)	2015-12-22	2025-03-06	더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템	(ｒ)-1-(4-(6-(2-(4-(3,3-디플루오로시클로부톡시)-6-메틸피리딘-2-일)아세트아미도)피리다진-3-일)-2-플루오로부틸)-ｎ-메틸-1ｈ-1,2,3-트리아졸-4-카르복사미드의 염 형태 및 다형체
US10722487B2 (en)	2017-10-18	2020-07-28	Board Of Regents, The University Of Texas System	Glutaminase inhibitor therapy

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3833586A (en) *	1971-03-25	1974-09-03	Morton Norwich Products Inc	1-(substituted benzyl)-2-(1h)pyrimidones and 1-(substituted benzyl)tetrahydro-2-(1h)pyrimidones
GB1561290A (en) *	1975-10-16	1980-02-20	Nyegaard & Co As	Pyrimid - 2 - ones
US4003900A (en) *	1976-03-11	1977-01-18	Morton-Norwich Products, Inc.	1-Benzyl-5-chloro-2-(1H)-pyrimidone
US4052399A (en) *	1976-09-13	1977-10-04	Morton-Norwich Products, Inc.	1-[2-(Hexahydro-1H-azepino)ethyl]-2(1H)pyrimidone dihydrochloride
US4052400A (en) *	1976-10-29	1977-10-04	Morton-Norwich Products, Inc.	Hypertensive 1-substituted 2(1h)-pyrimidones

1981
- 1981-01-05 ES ES498337A patent/ES498337A0/es active Granted
- 1981-01-06 NO NO810024A patent/NO810024L/no unknown
- 1981-01-06 AT AT81300031T patent/ATE4715T1/de not_active IP Right Cessation
- 1981-01-06 US US06/222,959 patent/US4399140A/en not_active Expired - Fee Related
- 1981-01-06 CA CA000367958A patent/CA1168239A/en not_active Expired
- 1981-01-06 DE DE8181300031T patent/DE3160886D1/de not_active Expired
- 1981-01-06 IE IE13/81A patent/IE50765B1/en unknown
- 1981-01-06 JP JP63181A patent/JPS56150087A/ja active Pending
- 1981-01-06 DK DK003281AA patent/DK149892B/da unknown
- 1981-01-06 EP EP81300031A patent/EP0032131B1/de not_active Expired
- 1981-01-06 NZ NZ195947A patent/NZ195947A/xx unknown
- 1981-01-06 ZA ZA00810064A patent/ZA8164B/xx unknown
- 1981-01-06 AU AU66016/81A patent/AU543939B2/en not_active Ceased
1982
- 1982-02-01 ES ES509219A patent/ES8304946A1/es not_active Expired

Also Published As

Publication number	Publication date
AU543939B2 (en)	1985-05-09
ES509219A0 (es)	1983-03-16
NZ195947A (en)	1983-09-02
US4399140A (en)	1983-08-16
EP0032131B1 (de)	1983-09-21
IE810013L (en)	1981-07-07
ATE4715T1 (de)	1983-10-15
DK3281A (da)	1981-07-08
NO810024L (no)	1981-07-08
JPS56150087A (en)	1981-11-20
CA1168239A (en)	1984-05-29
ES8304946A1 (es)	1983-03-16
AU6601681A (en)	1981-07-16
ES8205399A1 (es)	1982-06-01
IE50765B1 (en)	1986-07-09
ZA8164B (en)	1982-03-31
ES498337A0 (es)	1982-06-01
EP0032131A1 (de)	1981-07-15
DE3160886D1 (en)	1983-10-27

Publication	Publication Date	Title
AU2014274644B2 (en)	2019-11-14	New thienopyrimidine derivatives, a process for their preparation and pharmaceutical compositions containing them
AU2017226004B2 (en)	2021-07-22	Inhibitors of WDR5 protein-protein binding
CA2990089C (en)	2020-11-03	New aminoacid derivatives, a process for their preparation and pharmaceutical compositions containing them
CA2990084A1 (en)	2016-12-29	Bicyclic derivatives, a process for their preparation and pharmaceutical compositions containing them
TW202108590A (zh)	2021-03-01	新穎羥基酸衍生物，其製備方法及含彼等之醫藥組合物
CZ300984B6 (cs)	2009-09-30	Benzazolové deriváty, jejich použití a farmaceutický prostredek
CA2899646A1 (en)	2014-09-18	Substituted xanthines and methods of use thereof
CA2823969A1 (en)	2012-07-12	2,4-diamino-6,7-dihydro-5h-pyrrolo[2,3]pyrimidine derivatives as fak/pyk2 inhibitors
WO2007040440A1 (en)	2007-04-12	New pyrimidine derivatives and their use in therapy as well as the use of pyrimidine derivatives in the manufacture of a medicament for prevention and/or treatment of alzheimer’s disease
HUE031540T2 (en)	2017-07-28	N- (4- (azaindazol-6-yl) phenyl) sulfonamides and their use as medicaments
EP3596084A1 (de)	2020-01-22	9,10,11,12-tetrahydro-8h-[1,4]diazepino[5',6':4,5]thieno[3,2-f]chinolin-8-on-verbindungen und verwendungen davon
JP2021513530A (ja)	2021-05-27	テトラヒドロイソキノリン化合物、その調製方法、そのような化合物を含む医薬組成物およびその使用
WO2024099440A1 (zh)	2024-05-16	一种稠环化合物、其用途及含其的药物组合物
CN114539225B (zh)	2024-02-20	2-氨基-嘧啶类化合物
EP0032131B1 (de)	1983-09-21	5-Halo-pyrimidin-2-one, ihre Salze, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Zusammensetzungen
EA016178B1 (ru)	2012-02-28	Соединения имидазолидинониламинопиримидина
Cao et al.	2024	Discovery of novel pyrazolo [1, 5-a] pyrimidine derivatives as selective ROCK2 inhibitors with anti-breast cancer migration and invasion activities
WO2017108204A1 (en)	2017-06-29	Novel substituted spiro-[indoline heterocycloalkane] compounds as phosphodiesterase inhibitors
CN103408540A (zh)	2013-11-27	2-唑环取代噻吩类plk1抑制剂及其用途
CN118176195A (zh)	2024-06-11	吡唑[3,4-d]嘧啶-3-酮类化合物及其医药用途
KR20190017996A (ko)	2019-02-20	Akt 억제제인 디히드로피라졸로아제핀계 화합물
KR100468352B1 (ko)	2005-01-27	신규 피라졸로피리미딘계 유도체, 그의 제조방법 및 이를 유효성분으로 하는 약학적 조성물
CN110229157A (zh)	2019-09-13	嘧啶并五元芳香杂环类化合物、其制备方法及用途
NO812432L (no)	1982-01-18	Fremgangsmaate for fremstilling av terapeutisk aktive pyrimidin-2-on-derivater.
CN119462522A (zh)	2025-02-18	N2-3-氟-5-取代苯基-2-氨基嘧啶类衍生物、其制备方法及医药用途