NO129205B - - Google Patents

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Info

Publication number: NO129205B
Authority: NO; Norway
Prior art keywords: pyrimidine; thieno; acid; morpholino; general formula
Prior art date: 1970-01-28

Application number

NO00283/71A

Other languages

English (en)

Norwegian (no)

Inventor

E Woitun

G Ohnacker

B Narr

U Horch

R Kadatz

Original Assignee

Thomae Gmbh Dr K

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.)

1970-01-28

Filing date

1971-01-27

Publication date

1974-03-11

1970-01-28 Priority claimed from DE19702003714 external-priority patent/DE2003714C/de

1970-11-26 Priority claimed from DE19702058085 external-priority patent/DE2058085A1/de

1970-11-26 Priority claimed from DE19702058086 external-priority patent/DE2058086A1/de

1971-01-27 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1974-03-11 Publication of NO129205B publication Critical patent/NO129205B/no

Links

150000001875 compounds Chemical class 0.000 claims description 43
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 26
239000002253 acid Substances 0.000 claims description 16
125000005843 halogen group Chemical group 0.000 claims description 13
239000003513 alkali Substances 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
238000000034 method Methods 0.000 claims description 11
125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 9
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 6
150000007522 mineralic acids Chemical class 0.000 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
235000005985 organic acids Nutrition 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
150000003230 pyrimidines Chemical class 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 124
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
238000002844 melting Methods 0.000 description 26
230000008018 melting Effects 0.000 description 26
235000011121 sodium hydroxide Nutrition 0.000 description 21
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 20
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
-1 carbethoxy- Chemical class 0.000 description 17
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 15
239000000284 extract Substances 0.000 description 15
238000010992 reflux Methods 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
239000002904 solvent Substances 0.000 description 14
238000001816 cooling Methods 0.000 description 13
239000000203 mixture Substances 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
239000004202 carbamide Substances 0.000 description 8
229960005141 piperazine Drugs 0.000 description 8
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
238000000354 decomposition reaction Methods 0.000 description 7
239000000047 product Substances 0.000 description 7
HKQMXHKNXRNUCF-UHFFFAOYSA-N 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C=12SC=CC2=NC(Cl)=NC=1N1CCOCC1 HKQMXHKNXRNUCF-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
210000001772 blood platelet Anatomy 0.000 description 6
238000009835 boiling Methods 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
239000005457 ice water Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 4
AQECFYPZMBRCIA-UHFFFAOYSA-N 2,4-dichlorothieno[3,2-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2SC=CC2=N1 AQECFYPZMBRCIA-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
230000007017 scission Effects 0.000 description 4
239000007858 starting material Substances 0.000 description 4
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
LQMMFVPUIVBYII-UHFFFAOYSA-N 2-methylmorpholine Chemical compound CC1CNCCO1 LQMMFVPUIVBYII-UHFFFAOYSA-N 0.000 description 3
CQSJDKGNONPQOQ-UHFFFAOYSA-N 3-aminothiophene-2-carboxylic acid Chemical compound NC=1C=CSC=1C(O)=O CQSJDKGNONPQOQ-UHFFFAOYSA-N 0.000 description 3
RNKPGHAHWMALFH-UHFFFAOYSA-N 4-(2-chloro-6-methylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C=12SC(C)=CC2=NC(Cl)=NC=1N1CCOCC1 RNKPGHAHWMALFH-UHFFFAOYSA-N 0.000 description 3
FYBPFTXUSFHANO-UHFFFAOYSA-N 4-(2-piperazin-1-ylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C1CNCCN1C1=NC(N2CCOCC2)=C(SC=C2)C2=N1 FYBPFTXUSFHANO-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
125000004414 alkyl thio group Chemical group 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
239000011521 glass Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000002594 sorbent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
ZDKZDOFEASCBMV-UHFFFAOYSA-N 2,4-dichloro-6-methylthieno[3,2-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2SC(C)=CC2=N1 ZDKZDOFEASCBMV-UHFFFAOYSA-N 0.000 description 2
HVUOYFFUWXEBMH-UHFFFAOYSA-N 2,4-dichloro-6-phenylthieno[3,2-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N1)C=C(S2)C2=CC=CC=C2)Cl HVUOYFFUWXEBMH-UHFFFAOYSA-N 0.000 description 2
WUXYWALKGQDXFI-UHFFFAOYSA-N 2,4-dichloro-7-methylthieno[3,2-d]pyrimidine Chemical compound N1=C(Cl)N=C2C(C)=CSC2=C1Cl WUXYWALKGQDXFI-UHFFFAOYSA-N 0.000 description 2
HPVVGJNZPMFWCI-UHFFFAOYSA-N 4-(2-chloro-6-phenylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C=12SC(C=3C=CC=CC=3)=CC2=NC(Cl)=NC=1N1CCOCC1 HPVVGJNZPMFWCI-UHFFFAOYSA-N 0.000 description 2
OYYSLCSAIRASKS-UHFFFAOYSA-N 4-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound N1=C(Cl)N=C2C(C)=CSC2=C1N1CCOCC1 OYYSLCSAIRASKS-UHFFFAOYSA-N 0.000 description 2
CNIDFKMQNJFLLR-UHFFFAOYSA-N 4-(6-methyl-2-piperazin-1-ylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound CC1=CC=2N=C(N=C(C2S1)N1CCOCC1)N1CCNCC1 CNIDFKMQNJFLLR-UHFFFAOYSA-N 0.000 description 2
XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-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
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000011324 bead Substances 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
150000007530 organic bases Chemical group 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
210000004623 platelet-rich plasma Anatomy 0.000 description 2
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 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
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 1
GIFBAFFFIHWBDP-UHFFFAOYSA-N 2,4-dichloro-6,7-dimethylthieno[3,2-d]pyrimidine Chemical compound ClC=1N=C(C2=C(N1)C(=C(S2)C)C)Cl GIFBAFFFIHWBDP-UHFFFAOYSA-N 0.000 description 1
NSMWYRLQHIXVAP-UHFFFAOYSA-N 2,5-dimethylpiperazine Chemical compound CC1CNC(C)CN1 NSMWYRLQHIXVAP-UHFFFAOYSA-N 0.000 description 1
HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
ZKBCQBSOBYLQKT-UHFFFAOYSA-N 4-(2-methylsulfanylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C=12SC=CC2=NC(SC)=NC=1N1CCOCC1 ZKBCQBSOBYLQKT-UHFFFAOYSA-N 0.000 description 1
JFIOBUYFSZTPKN-UHFFFAOYSA-N 4-(2-methylsulfonylthieno[3,2-d]pyrimidin-4-yl)morpholine Chemical compound C=12SC=CC2=NC(S(=O)(=O)C)=NC=1N1CCOCC1 JFIOBUYFSZTPKN-UHFFFAOYSA-N 0.000 description 1
ZEWWLZDNTOZATC-UHFFFAOYSA-N 4-thieno[3,2-d]pyrimidin-4-ylmorpholine Chemical class C1COCCN1C1=NC=NC2=C1SC=C2 ZEWWLZDNTOZATC-UHFFFAOYSA-N 0.000 description 1
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
XHCGHKKQNCZIHY-UHFFFAOYSA-N C(=O)(OCC)N1CCN(CC1)C=1N=C(C2=C(N1)C=CS2)S(=O)(=O)C Chemical compound C(=O)(OCC)N1CCN(CC1)C=1N=C(C2=C(N1)C=CS2)S(=O)(=O)C XHCGHKKQNCZIHY-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000012491 analyte Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
239000007767 bonding agent Substances 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical group C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 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
YICRPERKKBDRSP-UHFFFAOYSA-N methyl 3-amino-4-methylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC=C(C)C=1N YICRPERKKBDRSP-UHFFFAOYSA-N 0.000 description 1
QESSCNMSOLRYBO-UHFFFAOYSA-N methyl 3-amino-5-phenylthiophene-2-carboxylate Chemical compound NC1=C(C(=O)OC)SC(C=2C=CC=CC=2)=C1 QESSCNMSOLRYBO-UHFFFAOYSA-N 0.000 description 1
TWEQNZZOOFKOER-UHFFFAOYSA-N methyl 3-aminothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1N TWEQNZZOOFKOER-UHFFFAOYSA-N 0.000 description 1
NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229960003506 piperazine hexahydrate Drugs 0.000 description 1
AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
229940116357 potassium thiocyanate Drugs 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
239000008096 xylene Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

NO00283/71A 1970-01-28 1971-01-27 NO129205B (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE19702003714 DE2003714C (de)		1970-01-28	2 Piperazino 4 morpholino thieno eckige Klammer auf 3,2 d eckige Klammer zu pyrimidin und dessen Saureadditions salze
DE19702058085 DE2058085A1 (de)	1970-11-26	1970-11-26	Neues Verfahren zur Herstellung von 4-Morpholino-thieno[3,2-d]pyrimidinen
DE19702058086 DE2058086A1 (de)	1970-11-26	1970-11-26	Neue 4-Morpholino-thieno[3,2-d]pyrimidine,deren Salze und Verfahren zur Herstellung

Publications (1)

Publication Number	Publication Date
NO129205B true NO129205B (ja)	1974-03-11

Family

ID=27182372

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO00283/71A NO129205B (ja)	1970-01-28	1971-01-27

Country Status (9)

Country	Link
US (1)	US3763156A (ja)
AU (1)	AU2468871A (ja)
BE (1)	BE762135A (ja)
ES (2)	ES387554A1 (ja)
FR (1)	FR2081464B1 (ja)
GB (1)	GB1309182A (ja)
IL (1)	IL36079A0 (ja)
NL (1)	NL7101043A (ja)
NO (1)	NO129205B (ja)

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US6608053B2 (en) *	2000-04-27	2003-08-19	Yamanouchi Pharmaceutical Co., Ltd.	Fused heteroaryl derivatives
GB0423653D0 (en) *	2004-10-25	2004-11-24	Piramed Ltd	Pharmaceutical compounds
EP1847543A1 (de)	2006-04-19	2007-10-24	Boehringer Ingelheim Pharma GmbH & Co. KG	Dihydrothienopyrimidine zur Behandlung von entzündlichen Erkrankungen
EA013108B1 (ru) *	2006-04-19	2010-02-26	Бёрингер Ингельхайм Интернациональ Гмбх	Дигидротиенопиримидины для лечения воспалительных заболеваний
US7846929B2 (en) *	2006-04-26	2010-12-07	Genentech, Inc.	Phosphoinositide 3-kinase inhibitor compounds and methods of use
KR101422301B1 (ko)	2006-04-26	2014-07-30	에프. 호프만-라 로슈 아게	약학적 화합물
ES2347187T3 (es)	2006-04-26	2010-10-26	F. Hoffmann-La Roche Ag	Derivado de tieno(3,2-d)pirimidina, util como un inhibidor de pi3k.
US9487533B2 (en) *	2006-12-07	2016-11-08	Genentech, Inc.	Phosphoinositide 3-kinase inhibitor compounds and methods of use
BRPI0717923A2 (pt)	2006-12-07	2013-10-22	Genentech In	'' composto, composição farmacêutica, método para tratar um câncer, processo para a produção de uma composição farmacêutica, usos, métodos para inibir ou modular a atividade da lipídeo quinase e kit ' '
EP2207781B1 (en)	2007-09-24	2012-11-28	Genentech, Inc.	Thiazolopyrimidine p13k inhibitor compounds and methods of use
EP2380891B1 (de) *	2007-10-19	2013-12-11	Boehringer Ingelheim International Gmbh	Substituierte Piperidino-Dihydrothienopyrimidine
ATE537175T1 (de)	2007-10-19	2011-12-15	Boehringer Ingelheim Int	Neue piperazino-dihydrothienopyrimidin-derivate
KR20100075930A (ko) *	2007-10-19	2010-07-05	베링거 인겔하임 인터내셔날 게엠베하	헤테로사이클-치환된 피페라지노-디하이드로티에노피리미딘
EP2214675B1 (en)	2007-10-25	2013-11-20	Genentech, Inc.	Process for making thienopyrimidine compounds
GB0721095D0 (en) *	2007-10-26	2007-12-05	Piramed Ltd	Pharmaceutical compounds
AU2010224125B2 (en)	2009-03-12	2015-05-14	Genentech, Inc.	Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents for the treatment of hematopoietic malignancies
SG175708A1 (en) *	2009-05-27	2011-12-29	Genentech Inc	Bicyclic pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use
SG182247A1 (en) *	2009-05-27	2012-08-30	Hoffmann La Roche	Bicyclic indole-pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use
CA2776944A1 (en) *	2009-10-12	2011-05-12	F. Hoffmann-La Roche Ag	Combinations of a pi3k inhibitor and a mek inhibitor
CN103038643A (zh)	2010-04-16	2013-04-10	基因泰克公司	作为pi3k/akt激酶途径抑制剂效能的预测性生物标记的foxo3a
US20140004209A1 (en)	2010-12-22	2014-01-02	Genentech, Inc.	Autophagy inducer and inhibitor combination therapy for the treatment of neoplasms
US9802954B2 (en)	2011-08-24	2017-10-31	Boehringer Ingelheim International Gmbh	Piperidino-dihydrothienopyrimidine sulfoxides and their use for treating COPD and asthma
US20130059866A1 (en)	2011-08-24	2013-03-07	Boehringer Ingelheim International Gmbh	Novel piperidino-dihydrothienopyrimidine sulfoxides and their use for treating copd and asthma
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1971
- 1971-01-22 US US00108988A patent/US3763156A/en not_active Expired - Lifetime
- 1971-01-23 ES ES387554A patent/ES387554A1/es not_active Expired
- 1971-01-23 ES ES387553A patent/ES387553A1/es not_active Expired
- 1971-01-26 AU AU24688/71A patent/AU2468871A/en not_active Expired
- 1971-01-27 BE BE762135A patent/BE762135A/xx unknown
- 1971-01-27 NL NL7101043A patent/NL7101043A/xx unknown
- 1971-01-27 IL IL36079A patent/IL36079A0/xx unknown
- 1971-01-27 NO NO00283/71A patent/NO129205B/no unknown
- 1971-01-28 FR FR7102796A patent/FR2081464B1/fr not_active Expired
- 1971-04-19 GB GB2046471A patent/GB1309182A/en not_active Expired

Also Published As

Publication number	Publication date
ES387554A1 (es)	1974-01-16
ES387553A1 (es)	1974-01-16
AU2468871A (en)	1972-07-27
IL36079A0 (en)	1971-03-24
FR2081464B1 (ja)	1975-04-18
FR2081464A1 (ja)	1971-12-03
GB1309182A (en)	1973-03-07
BE762135A (fr)	1971-07-27
NL7101043A (ja)	1971-07-30
US3763156A (en)	1973-10-02

Publication	Publication Date	Title
NO129205B (ja)	1974-03-11
CA2985547C (en)	2024-02-20	Substituted tetrahydroquinolinone compounds as ror gamma modulators
JP2896532B2 (ja)	1999-05-31	新規なピリミジン誘導体およびその製造方法
FI63587C (fi)	1983-07-11	Foerfarande foer framstaellning av anti-inflammatoriska halogenerade 4-hydroxi-2-alkyl-3-karbamoyl-2h-tieno-1,2-tiazin-1,1-dioxidderivat
FI65435C (fi)	1984-05-10	Foerfarande foer framstaellning av immunitet raglerande och arrit motstaoende 5-(4-pyridyl)-6-(4-fluorfenyl)-2,3-dihydr oiidazo-(2,1-b)tiazol
CN105518005A (zh)	2016-04-20	作为rock抑制剂的三环吡啶-甲酰胺衍生物
JPH0784470B2 (ja)	1995-09-13	活性化合物、その製法及びそれを含む医薬組成物
NO179674B (no)	1996-08-19	Analogifremgangsmåte for fremstilling av terapeutisk aktive, heterosykliske N-oksidderivater av substituerte benzo[5,6Åsyklo-heptapyridiner
NO144514B (no)	1981-06-09	Skaftbefestigelse for husholdnings- og haveredskaper
CN102112450A (zh)	2011-06-29	5-炔基-嘧啶
CA3061209A1 (en)	2019-10-23	Compound used as autophagy regulator, and preparation method therefor and uses thereof
NO161373B (no)	1989-05-02	Analogifremgangsmaate for fremstilling av terapeutisk aktive pteridin-derivater.
NO152373B (no)	1985-06-10	Analogifremgangsmaate for fremstilling av farmakologisk aktive 8-fenyl-purin-derivater
NO160920B (no)	1989-03-06	Analogifremgangsm te for fremstilling av terapeutisk aktive 2-piperazino-pteridin-derivater.
FI61899C (fi)	1982-10-11	Foerfarande foer framstaellning av antiflogistiska och antitrombotiska 6-substituerad-3-amino-4-fenyl-1h-pyrazolo(3,4-b)pyridiner
DD216019A5 (de)	1984-11-28	Verfahren zur herstellung heterocyclisch ankondensierter pyrazolo (3,4-d) pyridin-3-one
JPH0499768A (ja)	1992-03-31	４―（４―フェニルピリジン―２―イル）ピペラジン―１―オキシド誘導体
NO172392B (no)	1993-04-05	Analogifremgangsmaate for fremstilling av 1h,3h-(1,2-c)-pyrrolo-7-tiazolkarboksamider
JP5635592B2 (ja)	2014-12-03	５−アルキニル−ピリジン
US3843663A (en)	1974-10-22	1,8-naphthyridine compounds
CS207619B2 (en)	1981-08-31	Method of making the new derivatives of 5,11-dihydro-6h-pyrido 2,3-b 1,4 benzodiazepin-6-on
NO812529L (no)	1982-01-25	Analogifremgangsmaate for fremstilling av terapeutisk aktive dibenzo-diazepin-derivater
DE2200764A1 (de)	1973-07-12	Neue thieno eckige klammer aff 2,3-d eckige klammer zu pyrimidine und verfahren zu ihrer herstellung
JPS58128384A (ja)	1983-07-30	ベンゾジオキシン化合物、その製造方法、および精神作用障害治療用医薬組成物
JPH07505394A (ja)	1995-06-15	橋渡しビスアリールカルビノール誘導体，組成物および使用法