JP3240192B2 - 置換ピリミジン類 - Google Patents

置換ピリミジン類

Info

Publication number: JP3240192B2
Authority: JP; Japan
Prior art keywords: compound; formula; methyl; pharmaceutically acceptable; pyrimidin
Prior art date: 1991-10-24
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

JP28588592A

Other languages

English (en)

Japanese (ja)

Other versions

JPH05222039A (ja

Inventor

ジョン・ワトソン・エリンボー

マドレーヌ・ニカイドー

ジェハン・フラムロズ・バグリ

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Wyeth LLC

Original Assignee

Wyeth LLC

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.)

1991-10-24

Filing date

1992-10-23

Publication date

2001-12-17

1991-10-24 Priority claimed from US07/782,025 external-priority patent/US5149699A/en

1992-04-07 Priority claimed from GB9207560A external-priority patent/GB2265899A/en

1992-06-25 Priority claimed from US07/901,485 external-priority patent/US5256654A/en

1992-10-23 Application filed by Wyeth LLC filed Critical Wyeth LLC

1993-08-31 Publication of JPH05222039A publication Critical patent/JPH05222039A/ja

2001-12-17 Application granted granted Critical

2001-12-17 Publication of JP3240192B2 publication Critical patent/JP3240192B2/ja

2016-12-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000003230 pyrimidines Chemical class 0.000 title description 6
238000000034 method Methods 0.000 claims abstract description 19
206010020772 Hypertension Diseases 0.000 claims abstract description 10
206010019280 Heart failures Diseases 0.000 claims abstract description 5
206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 4
238000002399 angioplasty Methods 0.000 claims abstract description 4
208000037803 restenosis Diseases 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract 5
150000001875 compounds Chemical class 0.000 claims description 66
-1 tri-n-butylstannyl Chemical group 0.000 claims description 41
150000003839 salts Chemical class 0.000 claims description 34
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
239000004327 boric acid Substances 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
150000001412 amines Chemical class 0.000 claims description 6
239000002585 base Substances 0.000 claims description 6
229910052763 palladium Inorganic materials 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
150000001204 N-oxides Chemical class 0.000 claims description 5
150000001540 azides Chemical class 0.000 claims description 5
QIHRCLRHOQGSMR-UHFFFAOYSA-N 2,4,6-trimethyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1C(C)CC2=C(C)N=C(C)N=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 QIHRCLRHOQGSMR-UHFFFAOYSA-N 0.000 claims description 4
PZOLYHWTYZJVKL-UHFFFAOYSA-N 2-methyl-8-[[6-[2-(2h-tetrazol-5-yl)phenyl]pyridin-3-yl]methyl]-4-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1CCC=2C(C(F)(F)F)=NC(C)=NC=2N1CC(C=N1)=CC=C1C1=CC=CC=C1C1=NN=NN1 PZOLYHWTYZJVKL-UHFFFAOYSA-N 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
239000003153 chemical reaction reagent Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
DFJVRDADHWRZFR-UHFFFAOYSA-N 2,4-dimethyl-7-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5h-pyrrolo[2,3-d]pyrimidin-6-one Chemical compound O=C1CC=2C(C)=NC(C)=NC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 DFJVRDADHWRZFR-UHFFFAOYSA-N 0.000 claims description 3
HPKMJTIQUSGVRH-UHFFFAOYSA-N 2,4-dimethyl-8-[[5-[2-(2h-tetrazol-5-yl)phenyl]pyridin-2-yl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(N=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 HPKMJTIQUSGVRH-UHFFFAOYSA-N 0.000 claims description 3
XSHXQLODFJYKON-UHFFFAOYSA-N 2,4-dimethyl-8-[[6-[2-(2h-tetrazol-5-yl)phenyl]pyridin-3-yl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=N1)=CC=C1C1=CC=CC=C1C1=NN=NN1 XSHXQLODFJYKON-UHFFFAOYSA-N 0.000 claims description 3
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 3
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 3
150000002978 peroxides Chemical class 0.000 claims description 3
229910000080 stannane Inorganic materials 0.000 claims description 3
XZSGKWRFINHUBU-UHFFFAOYSA-N 2-methyl-7-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-4-(trifluoromethyl)-5h-pyrrolo[2,3-d]pyrimidin-6-one Chemical compound O=C1CC=2C(C(F)(F)F)=NC(C)=NC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 XZSGKWRFINHUBU-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
239000002798 polar solvent Substances 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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 3
239000003795 chemical substances by application Substances 0.000 claims 2
238000005903 acid hydrolysis reaction Methods 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
230000005494 condensation Effects 0.000 claims 1
238000009833 condensation Methods 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 abstract description 5
239000000203 mixture Substances 0.000 description 81
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
239000000047 product Substances 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000000460 chlorine Substances 0.000 description 31
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
239000007787 solid Substances 0.000 description 30
239000000284 extract Substances 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
235000019439 ethyl acetate Nutrition 0.000 description 21
238000010992 reflux Methods 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 14
238000002844 melting Methods 0.000 description 13
230000008018 melting Effects 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000000243 solution Substances 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000012267 brine Substances 0.000 description 11
238000000921 elemental analysis Methods 0.000 description 11
238000000746 purification Methods 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
150000003536 tetrazoles Chemical class 0.000 description 8
230000004872 arterial blood pressure Effects 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
238000001665 trituration Methods 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012131 assay buffer Substances 0.000 description 6
239000006260 foam Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
102000005962 receptors Human genes 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
239000011734 sodium Substances 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
102000005862 Angiotensin II Human genes 0.000 description 5
101800000733 Angiotensin-2 Proteins 0.000 description 5
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 5
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 5
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
229950006323 angiotensin ii Drugs 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000002480 mineral oil Substances 0.000 description 5
235000010446 mineral oil Nutrition 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 4
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 4
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
230000003276 anti-hypertensive effect Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
150000002367 halogens Chemical class 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000001632 sodium acetate Substances 0.000 description 4
235000017281 sodium acetate Nutrition 0.000 description 4
239000000725 suspension Substances 0.000 description 4
ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 4
238000012360 testing method Methods 0.000 description 4
239000008096 xylene Substances 0.000 description 4
DJPPOMGPZWRNGQ-UHFFFAOYSA-N 2,4-dimethyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2C=CC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 DJPPOMGPZWRNGQ-UHFFFAOYSA-N 0.000 description 3
UMGWNXVFPXRTJJ-UHFFFAOYSA-N 2-methyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-4-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1CCC=2C(C(F)(F)F)=NC(C)=NC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 UMGWNXVFPXRTJJ-UHFFFAOYSA-N 0.000 description 3
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CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
150000001499 aryl bromides Chemical class 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
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GBRDREUTRFOKNX-UHFFFAOYSA-N ethyl 3-(4-chloro-2,6-dimethylpyrimidin-5-yl)propanoate Chemical compound CCOC(=O)CCC1=C(C)N=C(C)N=C1Cl GBRDREUTRFOKNX-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
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150000007529 inorganic bases Chemical class 0.000 description 3
238000005259 measurement Methods 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 3
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239000006228 supernatant Substances 0.000 description 3
NSSSVJYQTZRVMH-UHFFFAOYSA-N (6-methylpyridin-3-yl) trifluoromethanesulfonate Chemical compound CC1=CC=C(OS(=O)(=O)C(F)(F)F)C=N1 NSSSVJYQTZRVMH-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
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XLNJWYDKDLBIQT-UHFFFAOYSA-N 2-[4-[(2,4,6-trimethyl-7-oxo-5,6-dihydropyrido[2,3-d]pyrimidin-8-yl)methyl]phenyl]benzonitrile Chemical compound O=C1C(C)CC2=C(C)N=C(C)N=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C#N XLNJWYDKDLBIQT-UHFFFAOYSA-N 0.000 description 2
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JKWBEGVIOLLUJB-UHFFFAOYSA-N 2-methyl-4-(trifluoromethyl)-6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical compound N1C(=O)CCC2=C1N=C(C)N=C2C(F)(F)F JKWBEGVIOLLUJB-UHFFFAOYSA-N 0.000 description 2
PKXFTEXAADGGLM-UHFFFAOYSA-N 8-[[4-[2-(1-tert-butyltetrazol-5-yl)phenyl]phenyl]methyl]-2,4-dimethyl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1C(C)(C)C PKXFTEXAADGGLM-UHFFFAOYSA-N 0.000 description 2
101800000734 Angiotensin-1 Proteins 0.000 description 2
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IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-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
208000003098 Ganglion Cysts Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
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229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
201000008312 primary pulmonary hypertension Diseases 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
201000001474 proteinuria Diseases 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000036454 renin-angiotensin system Effects 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
208000037812 secondary pulmonary hypertension Diseases 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
UQCWXKSHRQJGPH-UHFFFAOYSA-M tetrabutylazanium;fluoride;hydrate Chemical compound O.[F-].CCCC[N+](CCCC)(CCCC)CCCC UQCWXKSHRQJGPH-UHFFFAOYSA-M 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Hospice & Palliative Care (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

JP28588592A 1991-10-24 1992-10-23 置換ピリミジン類 Expired - Fee Related JP3240192B2 (ja)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US07/782,025 US5149699A (en)	1991-10-24	1991-10-24	Substituted pyridopyrimidines useful as antgiotensin II antagonists
US782025		1991-10-24
GB9207560A GB2265899A (en)	1992-04-07	1992-04-07	Substituted pyrimidines
US9207560		1992-06-25
US07/901,485 US5256654A (en)	1991-10-24	1992-06-25	Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines useful as angiotensin II antagonists
US901485		1992-06-25

Publications (2)

Publication Number	Publication Date
JPH05222039A JPH05222039A (ja)	1993-08-31
JP3240192B2 true JP3240192B2 (ja)	2001-12-17

Family

ID=27266132

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP28588592A Expired - Fee Related JP3240192B2 (ja)	1991-10-24	1992-10-23	置換ピリミジン類

Country Status (21)

Country	Link
EP (1)	EP0539086B1 (2)
JP (1)	JP3240192B2 (2)
KR (1)	KR100286624B1 (2)
CN (2)	CN1039324C (2)
AT (1)	ATE161537T1 (2)
AU (1)	AU653635B2 (2)
CA (1)	CA2080705C (2)
DE (1)	DE69223734T2 (2)
DK (1)	DK0539086T3 (2)
ES (1)	ES2111617T3 (2)
FI (1)	FI103971B1 (2)
GR (1)	GR3025926T3 (2)
HK (1)	HK1003031A1 (2)
HU (2)	HU218786B (2)
IL (1)	IL103436A (2)
LV (1)	LV12047B (2)
NO (1)	NO301275B1 (2)
SG (1)	SG47626A1 (2)
SK (1)	SK280292B6 (2)
TW (1)	TW226375B (2)
UA (1)	UA27748C2 (2)

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DE69415706T2 (de) *	1993-03-24	1999-05-20	American Home Products Corp., Madison, N.J.	Substituierte Pyridopyrimidine als Antihypertensiva
DE69507887T2 (de) *	1994-09-20	1999-06-17	Wakunaga Seiyaku K.K., Osaka	Verfahren zur herstellung von n-biphenylmethylthiadiazolin derivaten oder deren salzen sowie dafür benötigte zwischen verbindungen
IT1292437B1 (it) *	1997-06-30	1999-02-08	Zambon Spa	Processo di orto-metallazione utile per la sintesi di 1 - tetrazol- 5-il) benzeni 2-sostituiti
US6638937B2 (en)	1998-07-06	2003-10-28	Bristol-Myers Squibb Co.	Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
PE20020617A1 (es)	2000-08-22	2002-08-05	Novartis Ag	Composicion que comprende un antagonista del receptor at1 y un potenciador de la secrecion de insulina o un sensibilizante a la insulina
US8168616B1 (en)	2000-11-17	2012-05-01	Novartis Ag	Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension
US7732162B2 (en)	2003-05-05	2010-06-08	Probiodrug Ag	Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases
GB0327839D0 (en)	2003-12-01	2003-12-31	Novartis Ag	Organic compounds
GB0402262D0 (en)	2004-02-02	2004-03-10	Novartis Ag	Process for the manufacture of organic compounds
NZ549535A (en)	2004-03-17	2010-11-26	Novartis Ag	Use of aliskiren for treating renal and other disorders
ES2384637T3 (es)	2004-10-08	2012-07-10	Novartis Ag	Uso de inhibidores de la renina para la prevención o el tratamiento de disfunción diastólica o insuficiencia cardiaca diastólica
EP1749828A1 (en)	2005-08-04	2007-02-07	Farmaprojects S.L.	Process for preparing an angiotensin II receptor antagonist
JP5930573B2 (ja)	2007-03-01	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤の新規使用
EP2142514B1 (en)	2007-04-18	2014-12-24	Probiodrug AG	Thiourea derivatives as glutaminyl cyclase inhibitors
MX354786B (es)	2007-06-04	2018-03-21	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
KR101530019B1 (ko) *	2007-06-07	2015-06-18	시그마타우 인두스트리에 파르마슈티케 리우니테 에스.피.에이.	혈관성형술 또는 동맥내막절제술 후 재협착 및 장기 섬유증으로 인한 질환의 치료에 유용한 5베타, 14베타-안드로스테인 유도체
ES2522968T3 (es)	2008-06-04	2014-11-19	Synergy Pharmaceuticals Inc.	Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos
AU2009270833B2 (en)	2008-07-16	2015-02-19	Bausch Health Ireland Limited	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
JP5934645B2 (ja)	2009-09-11	2016-06-15	プロビオドルグエージー	グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体
JP6026284B2 (ja)	2010-03-03	2016-11-16	プロビオドルグエージー	グルタミニルシクラーゼの阻害剤
NZ602312A (en)	2010-03-10	2014-02-28	Probiodrug Ag	Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5)
WO2011131748A2 (en)	2010-04-21	2011-10-27	Probiodrug Ag	Novel inhibitors
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
EP2686313B1 (en)	2011-03-16	2016-02-03	Probiodrug AG	Benzimidazole derivatives as inhibitors of glutaminyl cyclase
WO2013090196A1 (en)	2011-12-15	2013-06-20	Takeda Pharmaceuticals U.S.A., Inc.	Combinations of azilsartan and chlorthalidone for treating hypertension black patients
AU2014235215A1 (en)	2013-03-15	2015-10-01	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235209B2 (en)	2013-03-15	2018-06-14	Bausch Health Ireland Limited	Guanylate cyclase receptor agonists combined with other drugs
BR112015030326A2 (pt)	2013-06-05	2017-08-29	Synergy Pharmaceuticals Inc	Agonistas ultrapuros de guanilato ciclase c, método de fabricar e usar os mesmos
ES2812698T3 (es)	2017-09-29	2021-03-18	Probiodrug Ag	Inhibidores de glutaminil ciclasa

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US5100897A (en) *	1989-08-28	1992-03-31	Merck & Co., Inc.	Substituted pyrimidinones as angiotensin ii antagonists
EP0415886A3 (en) *	1989-08-30	1991-10-23	Ciba-Geigy Ag	Aza compounds
JPH05504969A (ja) *	1990-02-13	1993-07-29	メルク・エンド・カムパニー・インコーポレーテツド	置換ベンジル要素を含有するアンギオテンシン２アンタゴニスト類
US5149699A (en) *	1991-10-24	1992-09-22	American Home Products Corporation	Substituted pyridopyrimidines useful as antgiotensin II antagonists

1992
- 1992-08-27 TW TW081106755A patent/TW226375B/zh active
- 1992-09-30 FI FI924397A patent/FI103971B1/fi not_active IP Right Cessation
- 1992-10-01 AU AU26079/92A patent/AU653635B2/en not_active Ceased
- 1992-10-06 HU HU9203161A patent/HU218786B/hu not_active IP Right Cessation
- 1992-10-14 SG SG1996003253A patent/SG47626A1/en unknown
- 1992-10-14 ES ES92309333T patent/ES2111617T3/es not_active Expired - Lifetime
- 1992-10-14 DK DK92309333.0T patent/DK0539086T3/da active
- 1992-10-14 AT AT92309333T patent/ATE161537T1/de not_active IP Right Cessation
- 1992-10-14 EP EP92309333A patent/EP0539086B1/en not_active Expired - Lifetime
- 1992-10-14 DE DE69223734T patent/DE69223734T2/de not_active Expired - Fee Related
- 1992-10-15 IL IL10343692A patent/IL103436A/en not_active IP Right Cessation
- 1992-10-16 CA CA002080705A patent/CA2080705C/en not_active Expired - Fee Related
- 1992-10-23 JP JP28588592A patent/JP3240192B2/ja not_active Expired - Fee Related
- 1992-10-23 NO NO924121A patent/NO301275B1/no not_active IP Right Cessation
- 1992-10-23 CN CN92113781A patent/CN1039324C/zh not_active Expired - Fee Related
- 1992-10-23 KR KR1019920019580A patent/KR100286624B1/ko not_active Expired - Fee Related
- 1992-10-26 SK SK3221-92A patent/SK280292B6/sk unknown
1993
- 1993-06-18 UA UA93003129A patent/UA27748C2/uk unknown
1995
- 1995-06-29 HU HU95P/P00549P patent/HU211915A9/hu unknown
1997
- 1997-05-13 CN CN97111592A patent/CN1175414A/zh active Pending
1998
- 1998-01-15 GR GR980400096T patent/GR3025926T3/el unknown
- 1998-03-09 LV LVP-98-45A patent/LV12047B/en unknown
- 1998-03-12 HK HK98102075A patent/HK1003031A1/en not_active IP Right Cessation

Patent Citations (1)

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Publication number	Priority date	Publication date	Assignee	Title
WO1992014714A1 (en)	1991-02-16	1992-09-03	Fisons Plc	Substituted pyridinones and pyrimidinones as angiotensin ii antagonists

Also Published As

Publication number	Publication date
JPH05222039A (ja)	1993-08-31
FI924397A0 (fi)	1992-09-30
UA27748C2 (uk)	2000-10-16
KR930007949A (ko)	1993-05-20
FI103971B (fi)	1999-10-29
EP0539086A2 (en)	1993-04-28
KR100286624B1 (ko)	2001-05-02
LV12047B (en)	1998-08-20
HU211915A9 (en)	1996-01-29
DE69223734D1 (de)	1998-02-05
ES2111617T3 (es)	1998-03-16
FI924397L (fi)	1993-04-25
CN1072682A (zh)	1993-06-02
CA2080705A1 (en)	1993-04-25
ATE161537T1 (de)	1998-01-15
SG47626A1 (en)	1998-04-17
HUT62893A (en)	1993-06-28
AU653635B2 (en)	1994-10-06
GR3025926T3 (en)	1998-04-30
SK322192A3 (en)	1999-11-08
NO924121L (no)	1993-04-26
CA2080705C (en)	2002-12-03
IL103436A0 (en)	1993-03-15
AU2607992A (en)	1993-04-29
NO924121D0 (no)	1992-10-23
FI103971B1 (fi)	1999-10-29
HU218786B (hu)	2000-12-28
LV12047A (lv)	1998-05-20
HU9203161D0 (en)	1992-12-28
EP0539086B1 (en)	1997-12-29
NO301275B1 (no)	1997-10-06
CN1175414A (zh)	1998-03-11
SK280292B6 (sk)	1999-11-08
EP0539086A3 (en)	1993-06-16
IL103436A (en)	1996-03-31
HK1003031A1 (en)	1998-09-30
CN1039324C (zh)	1998-07-29
DE69223734T2 (de)	1998-04-16
DK0539086T3 (da)	1998-02-02
TW226375B (2)	1994-07-11

Legal Events

Date	Code	Title	Description
2004-10-12	LAPS	Cancellation because of no payment of annual fees

Publication	Publication Date	Title
JP3240192B2 (ja)	2001-12-17	置換ピリミジン類
US5149699A (en)	1992-09-22	Substituted pyridopyrimidines useful as antgiotensin II antagonists
US12077521B2 (en)	2024-09-03	Pyrazole derivatives as MALT1 inhibitors
HK1003031B (en)	1998-09-30	Condensed pyrimidine derivatives and their use as angiotensine ii antagonists
JP3260415B2 (ja)	2002-02-25	アンギオテンシンｉｉ拮抗作用を有する複素環化合物
US5225414A (en)	1993-07-06	Substituted azoles, a process for their preparation, and their use
KR100251822B1 (ko)	2000-09-01	고혈압치료제로서의 치환된 피리도피리미딘 및 이를 포함하는 약제학적 조성물
AU2004220382B2 (en)	2007-08-02	Imidazol-4-yl-ethynyl-pyridine derivatives
US5451583A (en)	1995-09-19	Substituted benzimidazoles and quinazolines as antihypertensives
US5256654A (en)	1993-10-26	Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines useful as angiotensin II antagonists
EP0618207B1 (en)	1999-01-07	Substituted pyridopyrimidines as antihypertensives
GB2265899A (en)	1993-10-13	Substituted pyrimidines
HK1011358B (en)	2000-04-28	Substituted pyridopyrimidines as antihypertensives