CH593281A5 - Antibacterial piperazine derivs and inters - prepd. from 4-substd. amino-2-substd. pyrimidine-5-carboxylic acid esters - Google Patents

Antibacterial piperazine derivs and inters - prepd. from 4-substd. amino-2-substd. pyrimidine-5-carboxylic acid esters

Info

Publication number: CH593281A5
Authority: CH; Switzerland
Prior art keywords: ethyl; pyrimidine; piperazinyl; product; compound
Prior art date: 1973-04-03

Application number

CH205474A

Other languages

German (de)

English (en)

Original Assignee

Dainippon Pharmaceutical Co

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.)

1973-04-03

Filing date

1974-02-14

Publication date

1977-11-30

1973-04-03 Priority claimed from JP3845373A external-priority patent/JPS5546400B2/ja

1973-05-21 Priority claimed from JP5654473A external-priority patent/JPS565753B2/ja

1973-06-07 Priority claimed from JP6446473A external-priority patent/JPS565755B2/ja

1974-02-14 Application filed by Dainippon Pharmaceutical Co filed Critical Dainippon Pharmaceutical Co

1977-11-30 Publication of CH593281A5 publication Critical patent/CH593281A5/de

Links

230000000844 anti-bacterial effect Effects 0.000 title abstract description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title abstract 4
IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical class OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 title 1
125000002252 acyl group Chemical group 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 11
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 claims abstract description 7
150000003839 salts Chemical class 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 54
-1 4-methyl -1-piperazinyl Chemical group 0.000 claims description 36
239000000047 product Substances 0.000 claims description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 24
239000000203 mixture Substances 0.000 claims description 24
238000000034 method Methods 0.000 claims description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 19
239000002904 solvent Substances 0.000 claims description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
238000010438 heat treatment Methods 0.000 claims description 13
238000001816 cooling Methods 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
239000007787 solid Substances 0.000 claims description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
239000013067 intermediate product Substances 0.000 claims description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 7
238000010992 reflux Methods 0.000 claims description 7
239000007858 starting material Substances 0.000 claims description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
239000007788 liquid Substances 0.000 claims description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
CNRWEHBBGLCEHG-UHFFFAOYSA-N ethyl 3-(ethylamino)propanoate Chemical compound CCNCCC(=O)OCC CNRWEHBBGLCEHG-UHFFFAOYSA-N 0.000 claims description 4
238000002329 infrared spectrum Methods 0.000 claims description 4
238000000746 purification Methods 0.000 claims description 4
YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 claims description 4
238000007363 ring formation reaction Methods 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 3
CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 claims description 3
238000003756 stirring Methods 0.000 claims description 3
RUVUQOOKKGVDNN-UHFFFAOYSA-N 3-(ethylamino)propanenitrile Chemical compound CCNCCC#N RUVUQOOKKGVDNN-UHFFFAOYSA-N 0.000 claims description 2
ADIBMWKWRKIHTC-UHFFFAOYSA-N 8-ethyl-2-(4-methylpiperazin-1-yl)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCN(C)CC1 ADIBMWKWRKIHTC-UHFFFAOYSA-N 0.000 claims description 2
VTZLSXSXDFXLIN-UHFFFAOYSA-N CCN(C=C1C(C)=O)C(N=C(N2CCN(C)CC2)N=C2)=C2C1=O Chemical compound CCN(C=C1C(C)=O)C(N=C(N2CCN(C)CC2)N=C2)=C2C1=O VTZLSXSXDFXLIN-UHFFFAOYSA-N 0.000 claims description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
238000000862 absorption spectrum Methods 0.000 claims description 2
229950005228 bromoform Drugs 0.000 claims description 2
239000006227 byproduct Substances 0.000 claims description 2
150000007942 carboxylates Chemical class 0.000 claims description 2
238000000605 extraction Methods 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
239000002244 precipitate Substances 0.000 claims description 2
238000001953 recrystallisation Methods 0.000 claims description 2
239000000741 silica gel Substances 0.000 claims description 2
229910002027 silica gel Inorganic materials 0.000 claims description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
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 claims description 2
239000003814 drug Substances 0.000 abstract description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
238000006798 ring closing metathesis reaction Methods 0.000 abstract 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 17
241000699670 Mus sp. Species 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
239000000243 solution Substances 0.000 description 9
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
208000015181 infectious disease Diseases 0.000 description 8
239000000725 suspension Substances 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
230000003647 oxidation Effects 0.000 description 7
238000007254 oxidation reaction Methods 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
238000007912 intraperitoneal administration Methods 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
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 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000012670 alkaline solution Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
125000001589 carboacyl group Chemical group 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
150000004885 piperazines Chemical class 0.000 description 3
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 3
238000005303 weighing Methods 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
238000006228 Dieckmann condensation reaction Methods 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
241000589517 Pseudomonas aeruginosa Species 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
210000003608 fece Anatomy 0.000 description 2
KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
235000015097 nutrients Nutrition 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
239000011734 sodium Substances 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
KOMRHPHTMKCPCD-UHFFFAOYSA-N 1,2-dimethoxyethanol Chemical compound COCC(O)OC KOMRHPHTMKCPCD-UHFFFAOYSA-N 0.000 description 1
QCZZSANNLWPGEA-UHFFFAOYSA-N 1-(4-phenylphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=CC=C1 QCZZSANNLWPGEA-UHFFFAOYSA-N 0.000 description 1
QTYNSBZQSZICCP-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-8-ethyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound C(C)(=O)N1CCN(CC1)C=1N=CC2=C(N1)N(CC(C2=O)C#N)CC QTYNSBZQSZICCP-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
DEIDCZQXRLZXEO-UHFFFAOYSA-N 8-ethyl-2-(4-ethylpiperazin-1-yl)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1CN(CC)CCN1C1=NC=C2C(=O)C(C(O)=O)=CN(CC)C2=N1 DEIDCZQXRLZXEO-UHFFFAOYSA-N 0.000 description 1
XBAFTLBBMNKRKN-UHFFFAOYSA-N 8-ethyl-2-(4-methylpiperazin-1-yl)-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound C(C)N1CC(C(C2=C1N=C(N=C2)N2CCN(CC2)C)=O)C#N XBAFTLBBMNKRKN-UHFFFAOYSA-N 0.000 description 1
241001478240 Coccus Species 0.000 description 1
241000588722 Escherichia Species 0.000 description 1
102000009338 Gastric Mucins Human genes 0.000 description 1
108010009066 Gastric Mucins Proteins 0.000 description 1
PQMWYJDJHJQZDE-UHFFFAOYSA-M Methantheline bromide Chemical compound [Br-].C1=CC=C2C(C(=O)OCC[N+](C)(CC)CC)C3=CC=CC=C3OC2=C1 PQMWYJDJHJQZDE-UHFFFAOYSA-M 0.000 description 1
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
241000607768 Shigella Species 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
150000001298 alcohols Chemical class 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
150000001350 alkyl halides Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
229910001863 barium hydroxide Inorganic materials 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
150000001734 carboxylic acid salts Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000007809 chemical reaction catalyst Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
GEDDAQGDMDKEMO-UHFFFAOYSA-N ethyl 2-(4-acetylpiperazin-1-yl)-8-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(CC)C2=NC=1N1CCN(C(C)=O)CC1 GEDDAQGDMDKEMO-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000002054 inoculum Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
SAFWHKYSCUAGHQ-UHFFFAOYSA-N sodium;hypoiodite Chemical compound [Na+].I[O-] SAFWHKYSCUAGHQ-UHFFFAOYSA-N 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
NLDYACGHTUPAQU-UHFFFAOYSA-N tetracyanoethylene Chemical group N#CC(C#N)=C(C#N)C#N NLDYACGHTUPAQU-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
239000008096 xylene 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CH205474A 1973-04-03 1974-02-14 Antibacterial piperazine derivs and inters - prepd. from 4-substd. amino-2-substd. pyrimidine-5-carboxylic acid esters CH593281A5 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
JP3845373A JPS5546400B2 (es)	1973-04-03	1973-04-03
JP5654473A JPS565753B2 (es)	1973-05-21	1973-05-21
JP6446473A JPS565755B2 (es)	1973-06-07	1973-06-07

Publications (1)

Publication Number	Publication Date
CH593281A5 true CH593281A5 (en)	1977-11-30

Family

ID=27289838

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH205474A CH593281A5 (en)	1973-04-03	1974-02-14	Antibacterial piperazine derivs and inters - prepd. from 4-substd. amino-2-substd. pyrimidine-5-carboxylic acid esters

Country Status (11)

Country	Link
AR (2)	AR204003A1 (es)
AT (1)	AT340931B (es)
CA (1)	CA1066701A (es)
CH (1)	CH593281A5 (es)
ES (1)	ES424851A1 (es)
FI (1)	FI56011C (es)
IE (1)	IE39102B1 (es)
NL (1)	NL186087C (es)
NO (1)	NO142221C (es)
PH (2)	PH10529A (es)
SE (1)	SE416051B (es)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IT1209163B (it) *	1979-12-21	1989-07-10	Unibios S P A Trecate Novara	Procedimento per la fabbricazione di: 6-alcossicarbonil-8-etil-5-oxo-5,8diidro-aperta par. quadrata 2,3-dchiusa par. quadrata-primidine 2-sostituite ed acidi libri corrispondenti.
CA2766100C (en)	2009-06-29	2018-05-22	Incyte Corporation	Pyrimidinones as pi3k inhibitors
WO2011075643A1 (en)	2009-12-18	2011-06-23	Incyte Corporation	Substituted heteroaryl fused derivatives as pi3k inhibitors
WO2011075630A1 (en)	2009-12-18	2011-06-23	Incyte Corporation	Substituted fused aryl and heteroaryl derivatives as pi3k inhibitors
ES2764848T3 (es)	2010-12-20	2020-06-04	Incyte Holdings Corp	N-(1-(fenilo sustituido)etilo)-9H-purina-6-aminas como inhibidores de PI3K
KR102131612B1 (ko)	2011-09-02	2020-07-08	인사이트 홀딩스 코포레이션	Ｐｉ３ｋ 억제제로서 헤테로시클릴아민
AR090548A1 (es)	2012-04-02	2014-11-19	Incyte Corp	Azaheterociclobencilaminas biciclicas como inhibidores de pi3k
WO2015191677A1 (en)	2014-06-11	2015-12-17	Incyte Corporation	Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors
SI3831833T1 (sl)	2015-02-27	2023-03-31	Incyte Holdings Corporation	Postopki za pripravo inhibitorja PI3K
WO2016183063A1 (en)	2015-05-11	2016-11-17	Incyte Corporation	Crystalline forms of a pi3k inhibitor
WO2016183060A1 (en)	2015-05-11	2016-11-17	Incyte Corporation	Process for the synthesis of a phosphoinositide 3-kinase inhibitor
IL278889B2 (en)	2018-06-01	2025-11-01	Incyte Corp	Dosing regimen for the treatment of pi3k related disorders

1974
- 1974-01-01 AR AR253060A patent/AR204003A1/es active
- 1974-01-30 CA CA191,286A patent/CA1066701A/en not_active Expired
- 1974-02-01 SE SE7401361A patent/SE416051B/xx not_active IP Right Cessation
- 1974-02-04 NO NO740349A patent/NO142221C/no unknown
- 1974-02-04 FI FI298/74A patent/FI56011C/fi active
- 1974-02-04 NL NLAANVRAGE7401509,A patent/NL186087C/xx not_active IP Right Cessation
- 1974-02-14 CH CH205474A patent/CH593281A5/de not_active IP Right Cessation
- 1974-03-25 IE IE00650/74A patent/IE39102B1/xx unknown
- 1974-04-02 ES ES424851A patent/ES424851A1/es not_active Expired
- 1974-04-03 AT AT277774A patent/AT340931B/de not_active IP Right Cessation
- 1974-04-03 PH PH15698A patent/PH10529A/en unknown
1975
- 1975-01-01 AR AR258571A patent/AR204660A1/es active
- 1975-09-05 PH PH17546A patent/PH10984A/en unknown

Also Published As

Publication number	Publication date
NO740349L (no)	1974-10-04
AT340931B (de)	1978-01-10
CA1066701A (en)	1979-11-20
NL186087B (nl)	1990-04-17
FI56011B (fi)	1979-07-31
IE39102B1 (en)	1978-08-02
NO142221B (no)	1980-04-08
AR204003A1 (es)	1975-11-12
IE39102L (en)	1974-10-03
SE416051B (sv)	1980-11-24
NO142221C (no)	1980-07-16
PH10984A (en)	1977-10-18
NL186087C (nl)	1990-09-17
ES424851A1 (es)	1976-06-01
FI56011C (fi)	1979-11-12
PH10529A (en)	1977-05-30
AR204660A1 (es)	1976-02-20
NL7401509A (es)	1974-10-07
ATA277774A (de)	1977-05-15

Publication	Publication Date	Title
DE1620649C3 (de)	1979-07-19	U-Dmydro-l-hydroxy-2-iinino,4,6diamino-pyrimidine sowie Verfahren zu deren Herstellung
DE2264163C2 (de)	1983-09-15	Substituierte 6,7-Dihydro-1-oxo-1H,5H-benzo[ij]chinolizin-2-carbonsäuren
US3755340A (en)	1973-08-28	Amino derivatives of pyrazolopyridine carboxylic acids and esters
DE2300491A1 (de)	1973-07-19	Neue pyrrolo eckige klammer auf 3,4-b eckige klammer zu pyrazinderivate, ihre herstellung und die medizinischen zusammensetzungen, die sie enthalten
DE2519730A1 (de)	1975-11-20	Benzochinonderivate, verfahren zu ihrer herstellung und ihre verwendung
CH593281A5 (en)	1977-11-30	Antibacterial piperazine derivs and inters - prepd. from 4-substd. amino-2-substd. pyrimidine-5-carboxylic acid esters
DE2003430A1 (de)	1970-09-03	Phenoxy-alkyl-carbonsaeurederivate
EP0187376A2 (de)	1986-07-16	6,7-Disubstituierte 1-Cyclopropyl-1,4-dihydro-4-oxo-1,8-naphthyridin-3-carbonsäuren
DE2333603A1 (de)	1974-01-31	Neue derivate von dipyrazolopyridinen und ihre salze
DE2341146A1 (de)	1974-02-28	Piperazinderivate sowie verfahren zu deren herstellung und anwendung
DE2362553A1 (de)	1974-06-20	Neue piperazinderivate
DE2604748A1 (de)	1976-08-19	Aminoderivate von imidazo(4,5-b) pyridinen
US2266754A (en)	1941-12-23	Synthesis of vitamin
US3207660A (en)	1965-09-21	Process for inhibiting growth of microorganisms
DE1470314C3 (es)	1975-02-20
DE2301069A1 (de)	1973-07-19	Neue isoindolinderivate, ihre herstellung und die medizinischen zusammensetzungen, die sie enthalten
DD144263A5 (de)	1980-10-08	Verfahren zur herstellung von furonaphthyridinverbindungen
CH617199A5 (en)	1980-05-14	Process for the preparation of pyrido[3,2-e]-as-triazine derivatives
EP0148742B1 (de)	1988-11-02	2-(2-Thienyl)-imidazo[4,5-b]pyridin-derivate und pharmazeutisch verträgliche Säureadditionssalze hiervon sowie Verfahren zu deren Herstellung
DE2137538A1 (de)	1972-06-29	Methoxyaminderivate und ihre Salze sowie ihre Verwendimg und Verfahren zur Herstellung derselben
AT328450B (de)	1976-03-25	Verfahren zur herstellung von neuen 6,7-dihydro-1-oxo-1h,5h-benzo (ij) chinolizin-2-carbonsaurederivaten, deren niederen alkylestern, amiden, hydraziden, halogeniden und salzen
DE2539504A1 (de)	1976-03-25	Pyrido eckige klammer auf 3,4-d eckige klammer zu pyridazine und verfahren zu ihrer herstellung
AT256107B (de)	1967-08-10	Verfahren zur Herstellung von neuen Aza-dibenzo-cycloheptenderivaten
US4190661A (en)	1980-02-26	Pyrazolo-quinolines, compositions and pharmaceutical preparations
AT357543B (de)	1980-07-10	Verfahren zur herstellung von pyrimidin- derivaten und deren salzen

Legal Events

Date	Code	Title	Description
1994-04-29	PL	Patent ceased
2024-10-31	PL	Patent ceased