NO311522B1 - Pyrimido[5,4-d]pyrimidiner, legemiddel inneholdende disse forbindelser, deres anvendelse og fremgangsmåte for fremstillingderav - Google Patents

Pyrimido[5,4-d]pyrimidiner, legemiddel inneholdende disse forbindelser, deres anvendelse og fremgangsmåte for fremstillingderav Download PDF

Info

Publication number: NO311522B1
Authority: NO; Norway
Prior art keywords: amino; group; phenyl; pyrimido; pyrimidine
Prior art date: 1996-03-06

Application number

NO19984082A

Other languages

English (en)

Norwegian (no)

Other versions

NO984082D0 (no

NO984082L (no

Inventor

Frank Himmelsbach

Georg Dahmann

Thomas Von Rueden

Thomas Metz

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.)

1996-03-06

Filing date

1998-09-04

Publication date

2001-12-03

1998-09-04 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1998-09-04 Publication of NO984082D0 publication Critical patent/NO984082D0/no

1998-09-04 Publication of NO984082L publication Critical patent/NO984082L/no

2001-12-03 Publication of NO311522B1 publication Critical patent/NO311522B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 143
JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 title claims description 28
239000003814 drug Substances 0.000 title claims description 5
238000002360 preparation method Methods 0.000 title claims description 5
229940079593 drug Drugs 0.000 title claims description 4
238000000034 method Methods 0.000 title description 6
-1 3-chlorophenyl- Chemical group 0.000 claims description 763
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 105
238000006243 chemical reaction Methods 0.000 claims description 77
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
150000003839 salts Chemical class 0.000 claims description 24
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 20
230000003647 oxidation Effects 0.000 claims description 17
238000007254 oxidation reaction Methods 0.000 claims description 17
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 16
238000004519 manufacturing process Methods 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
125000003277 amino group Chemical group 0.000 claims description 13
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
230000035755 proliferation Effects 0.000 claims description 9
125000003282 alkyl amino group Chemical group 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
125000001841 imino group Chemical group [H]N=* 0.000 claims description 7
206010028980 Neoplasm Diseases 0.000 claims description 6
125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 6
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
230000032050 esterification Effects 0.000 claims description 5
238000005886 esterification reaction Methods 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
DTNQTMAGMDRICO-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1C1CCN(C=2N=C3C(NC=4C=C(Cl)C(F)=CC=4)=NC=NC3=CN=2)CC1 DTNQTMAGMDRICO-UHFFFAOYSA-N 0.000 claims description 5
150000007524 organic acids Chemical class 0.000 claims description 5
229910052701 rubidium Inorganic materials 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 4
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
DUIDQEZCITUJOU-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(2-piperazin-1-ylethyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCN1CCNCC1 DUIDQEZCITUJOU-UHFFFAOYSA-N 0.000 claims description 4
ZDCCULNSINBBDM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(piperidin-4-ylmethyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCC1CCNCC1 ZDCCULNSINBBDM-UHFFFAOYSA-N 0.000 claims description 4
SBRKZTRZGNOWNH-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-methyl-6-n-(1-methylpiperidin-4-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound N=1C=C2N=CN=C(NC=3C=C(Cl)C(F)=CC=3)C2=NC=1N(C)C1CCN(C)CC1 SBRKZTRZGNOWNH-UHFFFAOYSA-N 0.000 claims description 4
JKWQTABCEDZHMO-UHFFFAOYSA-N 6-(4-amino-4-methylpiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(C)(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 JKWQTABCEDZHMO-UHFFFAOYSA-N 0.000 claims description 4
HDBREMCJUIQJGV-HOMQSWHASA-N C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 HDBREMCJUIQJGV-HOMQSWHASA-N 0.000 claims description 4
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
230000010933 acylation Effects 0.000 claims description 4
238000005917 acylation reaction Methods 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
230000009435 amidation Effects 0.000 claims description 4
238000007112 amidation reaction Methods 0.000 claims description 4
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
150000001728 carbonyl compounds Chemical class 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000004185 ester group Chemical group 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
229940126601 medicinal product Drugs 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
235000005985 organic acids Nutrition 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
230000001681 protective effect Effects 0.000 claims description 4
238000005932 reductive alkylation reaction Methods 0.000 claims description 4
230000006103 sulfonylation Effects 0.000 claims description 4
238000005694 sulfonylation reaction Methods 0.000 claims description 4
NDZPCTMEAPKWLH-UHFFFAOYSA-N 1-[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-ol Chemical compound C1CC(O)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 NDZPCTMEAPKWLH-UHFFFAOYSA-N 0.000 claims description 3
JBJSTJGOHXNHES-UHFFFAOYSA-N 1-[4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CCNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 JBJSTJGOHXNHES-UHFFFAOYSA-N 0.000 claims description 3
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
OSTDHUNARBLCPT-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(1-methylpiperidin-3-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1N(C)CCCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OSTDHUNARBLCPT-UHFFFAOYSA-N 0.000 claims description 3
LHMSGUCCOMYASZ-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-piperidin-3-ylpyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CNCCC1 LHMSGUCCOMYASZ-UHFFFAOYSA-N 0.000 claims description 3
IDURNBGPECAQTH-UHFFFAOYSA-N 6-(3-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(N)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 IDURNBGPECAQTH-UHFFFAOYSA-N 0.000 claims description 3
LWAQHCQLCICHJH-UHFFFAOYSA-N 6-(3-aminopyrrolidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 LWAQHCQLCICHJH-UHFFFAOYSA-N 0.000 claims description 3
VORHRQJEKLYXKI-UHFFFAOYSA-N 6-(4-aminoazepan-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 VORHRQJEKLYXKI-UHFFFAOYSA-N 0.000 claims description 3
FPYLEGNPEQPDQD-UHFFFAOYSA-N 6-[4-(2-aminoethyl)piperazin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CN(CCN)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FPYLEGNPEQPDQD-UHFFFAOYSA-N 0.000 claims description 3
AULRBLCTTGRVFH-UHFFFAOYSA-N 6-n-(1-azabicyclo[2.2.2]octan-4-yl)-4-n-(3-chloro-4-fluorophenyl)-6-n-methylpyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(CC2)CCC12N(C)C(N=C12)=NC=C1N=CN=C2NC1=CC=C(F)C(Cl)=C1 AULRBLCTTGRVFH-UHFFFAOYSA-N 0.000 claims description 3
OWIRUOISYWMKMA-UHFFFAOYSA-N 6-n-[(4-aminophenyl)methyl]-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=CC(N)=CC=C1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OWIRUOISYWMKMA-UHFFFAOYSA-N 0.000 claims description 3
XISRKIUFBITOLV-UHFFFAOYSA-N 6-n-[4-(aminomethyl)cyclohexyl]-4-n-(3-chloro-4-fluorophenyl)-6-n-methylpyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound N=1C=C2N=CN=C(NC=3C=C(Cl)C(F)=CC=3)C2=NC=1N(C)C1CCC(CN)CC1 XISRKIUFBITOLV-UHFFFAOYSA-N 0.000 claims description 3
XBARGVDOISHQKQ-HOMQSWHASA-N C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 XBARGVDOISHQKQ-HOMQSWHASA-N 0.000 claims description 3
GYJZOWPUMTUSEE-HDJSIYSDSA-N C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](C(=O)N2CCOCC2)CC1 Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](C(=O)N2CCOCC2)CC1 GYJZOWPUMTUSEE-HDJSIYSDSA-N 0.000 claims description 3
NJHIXVCSVBZKRX-UMSPYCQHSA-N ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] Chemical compound ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] NJHIXVCSVBZKRX-UMSPYCQHSA-N 0.000 claims description 3
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
206010027476 Metastases Diseases 0.000 claims description 3
VFCBLKHHSOCJBA-HDJSIYSDSA-N NC1=C(C=C(C=C1Cl)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)C(=O)N2CCCC2)Cl Chemical compound NC1=C(C=C(C=C1Cl)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)C(=O)N2CCCC2)Cl VFCBLKHHSOCJBA-HDJSIYSDSA-N 0.000 claims description 3
XWJDVVZLQSQCAV-UMSPYCQHSA-N Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O Chemical compound Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O XWJDVVZLQSQCAV-UMSPYCQHSA-N 0.000 claims description 3
206010029113 Neovascularisation Diseases 0.000 claims description 3
QSZHGXSBFPKSFU-UHFFFAOYSA-N [1-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]cyclopentyl]methanol Chemical compound N=1C=C2N=CN=C(NC=3C=C(Cl)C(F)=CC=3)C2=NC=1NC1(CO)CCCC1 QSZHGXSBFPKSFU-UHFFFAOYSA-N 0.000 claims description 3
KMHLXHOWFPMNMT-UHFFFAOYSA-N [4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperazin-1-yl]-morpholin-4-ylmethanone Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCN1CCN(C(=O)N2CCOCC2)CC1 KMHLXHOWFPMNMT-UHFFFAOYSA-N 0.000 claims description 3
230000002159 abnormal effect Effects 0.000 claims description 3
125000006309 butyl amino group Chemical group 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
230000009401 metastasis Effects 0.000 claims description 3
GFKYMYYJOGXQBW-UHFFFAOYSA-N methyl n-[3-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]propyl]carbamate Chemical compound C12=NC(NCCCNC(=O)OC)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GFKYMYYJOGXQBW-UHFFFAOYSA-N 0.000 claims description 3
FPZZRINZZMYKHL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-piperidin-4-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)C3CCNCC3)N=C12 FPZZRINZZMYKHL-UHFFFAOYSA-N 0.000 claims description 3
OMVYAPIWXONNFV-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxan-4-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1CCOCC1 OMVYAPIWXONNFV-UHFFFAOYSA-N 0.000 claims description 3
JGNKOJPHBUJTJZ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxolan-3-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1COCC1 JGNKOJPHBUJTJZ-UHFFFAOYSA-N 0.000 claims description 3
TWPVDIOCVXCQIV-UHFFFAOYSA-N n-[4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]cyclohexyl]-n-methylacetamide Chemical compound C1CC(N(C)C(C)=O)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 TWPVDIOCVXCQIV-UHFFFAOYSA-N 0.000 claims description 3
210000003556 vascular endothelial cell Anatomy 0.000 claims description 3
BFTYQYYBQNXKDS-UHFFFAOYSA-N 4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)N(C)C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 BFTYQYYBQNXKDS-UHFFFAOYSA-N 0.000 claims description 2
YYHURUCEAOGAFA-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(4-morpholin-4-ylcyclohexyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCC(N2CCOCC2)CC1 YYHURUCEAOGAFA-UHFFFAOYSA-N 0.000 claims description 2
JSLIYIRAEYINIM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(4-pyrrolidin-1-ylcyclohexyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCC(N2CCCC2)CC1 JSLIYIRAEYINIM-UHFFFAOYSA-N 0.000 claims description 2
RVBKCXFOUAMDGX-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-[4-(4-methylpiperazin-1-yl)cyclohexyl]pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCN1C1CCC(NC=2N=C3C(NC=4C=C(Cl)C(F)=CC=4)=NC=NC3=CN=2)CC1 RVBKCXFOUAMDGX-UHFFFAOYSA-N 0.000 claims description 2
RYWBCODYRUCURN-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 RYWBCODYRUCURN-UHFFFAOYSA-N 0.000 claims description 2
OULCPNGKXGXZIG-UHFFFAOYSA-N 6-[3-(aminomethyl)piperidin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(CN)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OULCPNGKXGXZIG-UHFFFAOYSA-N 0.000 claims description 2
GJMXSLKSMVMHQM-UHFFFAOYSA-N 6-n-(2-amino-2-methylpropyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C12=NC(NCC(C)(N)C)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GJMXSLKSMVMHQM-UHFFFAOYSA-N 0.000 claims description 2
HGFKQQJZAJZDRG-HAQNSBGRSA-N ClC=1C=C(C=CC1F)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)CN Chemical compound ClC=1C=C(C=CC1F)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)CN HGFKQQJZAJZDRG-HAQNSBGRSA-N 0.000 claims description 2
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
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ITCIBDVFVYZTFX-UHFFFAOYSA-N methyl 4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1CCNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 ITCIBDVFVYZTFX-UHFFFAOYSA-N 0.000 description 1
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QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
230000035778 pathophysiological process Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
IPOVLZSJBYKHHU-UHFFFAOYSA-N piperidin-3-ylmethanamine Chemical compound NCC1CCCNC1 IPOVLZSJBYKHHU-UHFFFAOYSA-N 0.000 description 1
LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 1
XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
238000007747 plating Methods 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940072033 potash Drugs 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
239000011833 salt mixture Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000007873 sieving Methods 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
238000009097 single-agent therapy Methods 0.000 description 1
238000005245 sintering Methods 0.000 description 1
NVIFVTYDZMXWGX-UHFFFAOYSA-N sodium metaborate Chemical compound [Na+].[O-]B=O NVIFVTYDZMXWGX-UHFFFAOYSA-N 0.000 description 1
229960001922 sodium perborate Drugs 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 1
APFUDGDIIFSTSD-UHFFFAOYSA-N tert-butyl 3-carbamoylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(C(N)=O)C1 APFUDGDIIFSTSD-UHFFFAOYSA-N 0.000 description 1
KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 1
KCHBUNJBZZZKKN-UHFFFAOYSA-N tert-butyl 4-[[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 KCHBUNJBZZZKKN-UHFFFAOYSA-N 0.000 description 1
YCOKHOLOSGJEGL-UHFFFAOYSA-N tert-butyl 4-aminoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)CC1 YCOKHOLOSGJEGL-UHFFFAOYSA-N 0.000 description 1
LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
KCBBEHBEAPOBSC-UHFFFAOYSA-N tert-butyl n-(2-amino-2-methylpropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(C)(C)N KCBBEHBEAPOBSC-UHFFFAOYSA-N 0.000 description 1
HMMYZMWDTDJTRR-UHFFFAOYSA-N tert-butyl n-[(4-aminocyclohexyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCC(N)CC1 HMMYZMWDTDJTRR-UHFFFAOYSA-N 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000007306 turnover Effects 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

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

NO19984082A 1996-03-06 1998-09-04 Pyrimido[5,4-d]pyrimidiner, legemiddel inneholdende disse forbindelser, deres anvendelse og fremgangsmåte for fremstillingderav NO311522B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19608588A DE19608588A1 (de)	1996-03-06	1996-03-06	Pyrimido [5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
PCT/EP1997/001047 WO1997032880A1 (de)	1996-03-06	1997-03-03	PYRIMIDO[5,4-d]PYRIMIDINE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG

Publications (3)

Publication Number	Publication Date
NO984082D0 NO984082D0 (no)	1998-09-04
NO984082L NO984082L (no)	1998-09-04
NO311522B1 true NO311522B1 (no)	2001-12-03

Family

ID=7787345

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19984082A NO311522B1 (no)	1996-03-06	1998-09-04	Pyrimido[5,4-d]pyrimidiner, legemiddel inneholdende disse forbindelser, deres anvendelse og fremgangsmåte for fremstillingderav

Country Status (29)

Country	Link
US (1)	US5821240A (uk)
EP (1)	EP0888351B1 (uk)
JP (1)	JP2000506151A (uk)
KR (1)	KR19990087504A (uk)
CN (1)	CN1064362C (uk)
AR (1)	AR006108A1 (uk)
AT (1)	ATE252101T1 (uk)
AU (1)	AU730376B2 (uk)
BG (1)	BG63163B1 (uk)
BR (1)	BR9707839A (uk)
CA (1)	CA2248720A1 (uk)
CO (1)	CO4650043A1 (uk)
CZ (1)	CZ281598A3 (uk)
DE (2)	DE19608588A1 (uk)
EE (1)	EE9800278A (uk)
HU (1)	HUP9902049A3 (uk)
IL (1)	IL125342A0 (uk)
MX (1)	MX9807073A (uk)
NO (1)	NO311522B1 (uk)
NZ (1)	NZ331545A (uk)
PL (1)	PL328719A1 (uk)
RU (1)	RU2195461C2 (uk)
SK (1)	SK120898A3 (uk)
TR (1)	TR199801755T2 (uk)
TW (1)	TW454008B (uk)
UA (1)	UA54421C2 (uk)
UY (1)	UY24474A1 (uk)
WO (1)	WO1997032880A1 (uk)
ZA (1)	ZA971887B (uk)

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU719434B2 (en)	1996-02-13	2000-05-11	Astrazeneca Ab	Quinazoline derivatives as VEGF inhibitors
ES2169355T3 (es)	1996-03-05	2002-07-01	Astrazeneca Ab	Derivados de 4-anilinoquinazolina.
US6028183A (en)	1997-11-07	2000-02-22	Gilead Sciences, Inc.	Pyrimidine derivatives and oligonucleotides containing same
JP3270834B2 (ja) *	1999-01-27	2002-04-02	ファイザー・プロダクツ・インク	抗がん剤として有用なヘテロ芳香族二環式誘導体
EP1676845B1 (en)	1999-11-05	2008-06-11	AstraZeneca AB	New quinazoline derivatives
EP1170011A1 (en) *	2000-07-06	2002-01-09	Boehringer Ingelheim International GmbH	Novel use of inhibitors of the epidermal growth factor receptor
DE10115921A1 (de)	2001-03-30	2002-10-02	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von 4,6-Diaminopyrimido[5,4-d]pyrimidinen
EP1300146A1 (en) *	2001-10-03	2003-04-09	Boehringer Ingelheim International GmbH	Pharmaceutical composition for the treatment of animal mammary tumors
US20040242888A1 (en) *	2001-12-27	2004-12-02	Takae Ono	Process for producing 1-alkoxycarbonyl nitrogenous saturated heterocyclic derivative
WO2004087707A1 (en) *	2003-03-31	2004-10-14	Vernalis (Cambridge) Limited	Pyrazolopyrimidine compounds and their use in medicine
ATE525377T1 (de) *	2003-10-15	2011-10-15	Osi Pharm Inc	Imidazoä1,5-aüpyrazine als inhibitoren von tyrosinkinase
NZ547794A (en) *	2003-12-18	2009-11-27	Janssen Pharmaceutica Nv	Pyrido- and pyrimidopyrimidine derivatives as anti-proliferative agents
JO3088B1 (ar) *	2004-12-08	2017-03-15	Janssen Pharmaceutica Nv	مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف
NI200700147A (es)	2004-12-08	2019-05-10	Janssen Pharmaceutica Nv	Derivados de quinazolina inhibidores de cinasas dirigidos a multip
KR101139038B1 (ko) *	2005-06-28	2012-05-02	삼성전자주식회사	피리미도피리미딘 유도체 및 이를 이용한 유기 박막 트랜지스터
CA2654583C (en)	2006-07-13	2015-11-24	Janssen Pharmaceutica N.V.	Mtki quinazoline derivatives
AU2008265104B2 (en) *	2007-06-21	2013-09-12	Janssen Pharmaceutica Nv	Indolin-2-ones and aza-indolin-2-ones
GB0713602D0 (en) *	2007-07-12	2007-08-22	Syngenta Participations Ag	Chemical compounds
JP5536647B2 (ja)	2007-07-27	2014-07-02	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ピロロピリミジン
JP2009215259A (ja) *	2008-03-12	2009-09-24	Ube Ind Ltd	３−ハロゲノ−４−ヒドロカルビルオキシニトロベンゼン化合物の製造方法
TW201014860A (en) *	2008-09-08	2010-04-16	Boehringer Ingelheim Int	New chemical compounds
EP2349235A1 (en)	2008-11-07	2011-08-03	Triact Therapeutics, Inc.	Use of catecholic butane derivatives in cancer therapy
CA2752265A1 (en)	2009-02-17	2010-08-26	Boehringer Ingelheim International Gmbh	Pyrimido [5,4-d] pyrimidine derivatives for the inhibition of tyrosine kinases
WO2010099139A2 (en)	2009-02-25	2010-09-02	Osi Pharmaceuticals, Inc.	Combination anti-cancer therapy
JP2012519170A (ja)	2009-02-26	2012-08-23	オーエスアイ・ファーマシューティカルズ，エルエルシー	生体内の腫瘍細胞のｅｍｔステータスをモニターするためのｉｎｓｉｔｕ法
US8465912B2 (en)	2009-02-27	2013-06-18	OSI Pharmaceuticals, LLC	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
JP2012519281A (ja)	2009-02-27	2012-08-23	オーエスアイ・ファーマシューティカルズ，エルエルシー	間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法
WO2010099138A2 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
JP2012520893A (ja)	2009-03-18	2012-09-10	オーエスアイ・ファーマシューティカルズ，エルエルシー	Ｅｇｆｒ阻害薬及びｉｇｆ−１ｒ阻害剤の投与を含む組み合わせ癌治療
EP2510110A1 (en)	2009-11-13	2012-10-17	Pangaea Biotech S.L.	Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer
EP2468883A1 (en)	2010-12-22	2012-06-27	Pangaea Biotech S.L.	Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer
US9134297B2 (en)	2011-01-11	2015-09-15	Icahn School Of Medicine At Mount Sinai	Method and compositions for treating cancer and related methods
EP2492688A1 (en)	2011-02-23	2012-08-29	Pangaea Biotech, S.A.	Molecular biomarkers for predicting response to antitumor treatment in lung cancer
WO2012129145A1 (en)	2011-03-18	2012-09-27	OSI Pharmaceuticals, LLC	Nscle combination therapy
WO2012149014A1 (en)	2011-04-25	2012-11-01	OSI Pharmaceuticals, LLC	Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment
BR112014004762A2 (pt)	2011-08-31	2018-06-19	Genentech Inc	métodos de determinação da sensibilidade de crescimento de célula tumoral á inibição por um inibidor de quinase de egfr, de identificação de um paciente com câncer que provavelmente irá se beneficiar do tratamento com um inibidor de efgr, de tratamento de um câncer em um paciente, de seleção de uma terapia para um paciente com câncer e de determinação de superexpressão de gene erbb2 em uma célula
SG11201400996SA (en)	2011-09-30	2014-04-28	Genentech Inc	Diagnostic methylation markers of epithelial or mesenchymal phenotype and response to egfr kinase inhibitor in tumours or tumour cells
WO2013152252A1 (en)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
WO2013190089A1 (en)	2012-06-21	2013-12-27	Pangaea Biotech, S.L.	Molecular biomarkers for predicting outcome in lung cancer
EP2961412A4 (en)	2013-02-26	2016-11-09	Triact Therapeutics Inc	CANCER THERAPY
WO2014147246A1 (en)	2013-03-21	2014-09-25	INSERM (Institut National de la Santé et de la Recherche Médicale)	Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression
US9381246B2 (en)	2013-09-09	2016-07-05	Triact Therapeutics, Inc.	Cancer therapy
WO2015156674A2 (en)	2014-04-10	2015-10-15	Stichting Het Nederlands Kanker Instituut	Method for treating cancer
EP3699290A1 (en)	2014-12-24	2020-08-26	F. Hoffmann-La Roche AG	Therapeutic, diagnostic, and prognostic methods for cancer
EA201991528A1 (ru)	2016-12-22	2020-01-16	Эмджен Инк.	БЕНЗИЗОТИАЗОЛЬНЫЕ, ИЗОТИАЗОЛО[3,4-b]ПИРИДИНОВЫЕ, ХИНАЗОЛИНОВЫЕ, ФТАЛАЗИНОВЫЕ, ПИРИДО[2,3-d]ПИРИДАЗИНОВЫЕ И ПИРИДО[2,3-d]ПИРИМИДИНОВЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ G12C KRAS ДЛЯ ЛЕЧЕНИЯ РАКА ЛЕГКОГО, РАКА ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ ИЛИ КОЛОРЕКТАЛЬНОГО РАКА
JOP20190272A1 (ar)	2017-05-22	2019-11-21	Amgen Inc	مثبطات kras g12c وطرق لاستخدامها
ES2985118T3 (es)	2017-09-08	2024-11-04	Amgen Inc	Inhibidores de KRAS G12C y métodos de uso de los mismos
EP3788038B1 (en)	2018-05-04	2023-10-11	Amgen Inc.	Kras g12c inhibitors and methods of using the same
CA3099118A1 (en)	2018-05-04	2019-11-07	Amgen Inc.	Kras g12c inhibitors and methods of using the same
MA52564A (fr)	2018-05-10	2021-03-17	Amgen Inc	Inhibiteurs de kras g12c pour le traitement du cancer
MX2020012731A (es)	2018-06-01	2021-02-22	Amgen Inc	Inhibidores de kras g12c y metodos para su uso.
EP4268898A3 (en)	2018-06-11	2024-01-17	Amgen Inc.	Kras g12c inhibitors for treating cancer
EP3807276B1 (en)	2018-06-12	2025-12-10	Amgen Inc.	Kras g12c inhibitors encompassing a piperazine ring and use thereof in the treatment of cancer
EP3860608A1 (en)	2018-10-04	2021-08-11	INSERM (Institut National de la Santé et de la Recherche Médicale)	Egfr inhibitors for treating keratodermas
JP7516029B2 (ja)	2018-11-16	2024-07-16	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法
JP7454572B2 (ja)	2018-11-19	2024-03-22	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤及びその使用方法
JP7377679B2 (ja)	2018-11-19	2023-11-10	アムジエン・インコーポレーテツド	がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法
KR102875569B1 (ko)	2018-12-20	2025-10-23	암젠 인크	Kif18a 억제제
US12459932B2 (en)	2018-12-20	2025-11-04	Amgen Inc.	KIF18A inhibitors
MX419368B (es)	2018-12-20	2025-01-14	Amgen Inc	Heteroarilamidas utiles como inhibidores de kif18a
US12441736B2 (en)	2018-12-20	2025-10-14	Amgen Inc.	KIF18A inhibitors
EP3930845A1 (en)	2019-03-01	2022-01-05	Revolution Medicines, Inc.	Bicyclic heterocyclyl compounds and uses thereof
WO2020180768A1 (en)	2019-03-01	2020-09-10	Revolution Medicines, Inc.	Bicyclic heteroaryl compounds and uses thereof
EP3738593A1 (en)	2019-05-14	2020-11-18	Amgen, Inc	Dosing of kras inhibitor for treatment of cancers
KR20250159270A (ko)	2019-05-21	2025-11-10	암젠 인크	고체 상태 형태
EP4007752B1 (en)	2019-08-02	2025-09-24	Amgen Inc.	Kif18a inhibitors
WO2021026100A1 (en)	2019-08-02	2021-02-11	Amgen Inc.	Pyridine derivatives as kif18a inhibitors
WO2021026101A1 (en)	2019-08-02	2021-02-11	Amgen Inc.	Kif18a inhibitors
WO2021026099A1 (en)	2019-08-02	2021-02-11	Amgen Inc.	Kif18a inhibitors
MX2022004656A (es)	2019-10-24	2022-05-25	Amgen Inc	Derivados de piridopirimidina utiles como inhibidores de kras g12c y kras g12d en el tratamiento del cancer.
PH12022550988A1 (en)	2019-11-04	2023-10-09	Revolution Medicines Inc	Ras inhibitors
KR20220109408A (ko)	2019-11-04	2022-08-04	레볼루션 메디슨즈, 인크.	Ras 억제제
CN114901366A (zh)	2019-11-04	2022-08-12	锐新医药公司	Ras抑制剂
WO2021092115A1 (en)	2019-11-08	2021-05-14	Revolution Medicines, Inc.	Bicyclic heteroaryl compounds and uses thereof
AR120457A1 (es)	2019-11-14	2022-02-16	Amgen Inc	Síntesis mejorada del compuesto inhibidor de g12c de kras
CA3161156A1 (en)	2019-11-14	2021-05-20	Amgen Inc.	Improved synthesis of kras g12c inhibitor compound
WO2021108683A1 (en)	2019-11-27	2021-06-03	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
WO2021142026A1 (en)	2020-01-07	2021-07-15	Revolution Medicines, Inc.	Shp2 inhibitor dosing and methods of treating cancer
US20230131720A1 (en)	2020-02-03	2023-04-27	Boehringer Ingelheim International Gmbh	[1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS
US20230126204A1 (en)	2020-02-03	2023-04-27	Boehringer Ingelheim International Gmbh	[1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS
US11608343B2 (en)	2020-04-24	2023-03-21	Boehringer Ingelheim International Gmbh	Substituted pyrimido[5,4-d]pyrimidines as HER2 inhibitors
MX2022016355A (es)	2020-06-18	2023-04-03	Revolution Medicines Inc	Metodos para retardar, prevenir, y tratar la resistencia adquirida a inhibidores de ras.
CA3187757A1 (en)	2020-09-03	2022-03-24	Ethan AHLER	Use of sos1 inhibitors to treat malignancies with shp2 mutations
IL301298A (en)	2020-09-15	2023-05-01	Revolution Medicines Inc	Indole derivatives as RAS inhibitors in cancer therapy
AU2021409816A1 (en)	2020-12-22	2023-07-06	Qilu Regor Therapeutics Inc.	Sos1 inhibitors and uses thereof
WO2022221227A1 (en)	2021-04-13	2022-10-20	Nuvalent, Inc.	Amino-substituted heterocycles for treating cancers with egfr mutations
AR125782A1 (es)	2021-05-05	2023-08-16	Revolution Medicines Inc	Inhibidores de ras
AR125787A1 (es)	2021-05-05	2023-08-16	Revolution Medicines Inc	Inhibidores de ras
WO2022235866A1 (en)	2021-05-05	2022-11-10	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
AR127308A1 (es)	2021-10-08	2024-01-10	Revolution Medicines Inc	Inhibidores ras
CN119212994A (zh)	2021-12-17	2024-12-27	建新公司	作为shp2抑制剂的吡唑并吡嗪化合物
EP4227307A1 (en)	2022-02-11	2023-08-16	Genzyme Corporation	Pyrazolopyrazine compounds as shp2 inhibitors
JP2025509217A (ja)	2022-03-07	2025-04-11	アムジエン・インコーポレーテツド	４－メチル－２－プロパン－２－イル－ピリジン－３－カルボニトリルを調製するための方法
WO2023172940A1 (en)	2022-03-08	2023-09-14	Revolution Medicines, Inc.	Methods for treating immune refractory lung cancer
CN120504682A (zh)	2022-06-10	2025-08-19	锐新医药公司	大环ras抑制剂
JP2025536257A (ja)	2022-10-14	2025-11-05	ブラックダイアモンドセラピューティクス，インコーポレイティド	イソキノリンまたは６－ａｚａ－キノリン誘導体を使用してがんを治療する方法
KR20250133319A (ko)	2022-12-22	2025-09-05	베링거 인겔하임 인터내셔날 게엠베하	Her2 억제제의 결정형
KR20250164828A (ko)	2023-03-30	2025-11-25	레볼루션 메디슨즈, 인크.	Ras gtp 가수분해 유도를 위한 조성물 및 이의 용도
CN121263418A (zh)	2023-04-07	2026-01-02	锐新医药公司	大环ras抑制剂
KR20260005904A (ko)	2023-04-07	2026-01-12	레볼루션 메디슨즈, 인크.	매크로사이클릭 ras 억제제
TW202448897A (zh)	2023-04-14	2024-12-16	美商銳新醫藥公司	Ｒａｓ抑制劑之結晶形式、含有其之組合物及其使用方法
CN121100123A (zh)	2023-04-14	2025-12-09	锐新医药公司	Ras抑制剂的结晶形式
TW202508595A (zh)	2023-05-04	2025-03-01	美商銳新醫藥公司	用於ｒａｓ相關疾病或病症之組合療法
WO2025026901A1 (en)	2023-07-28	2025-02-06	Boehringer Ingelheim International Gmbh	Process for the manufacture of a her2 inhibitor
US20250049810A1 (en)	2023-08-07	2025-02-13	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025080946A2 (en)	2023-10-12	2025-04-17	Revolution Medicines, Inc.	Ras inhibitors
TW202542151A (zh)	2023-12-22	2025-11-01	美商銳格醫藥有限公司	Ｓｏｓ１抑制劑及其用途
WO2025171296A1 (en)	2024-02-09	2025-08-14	Revolution Medicines, Inc.	Ras inhibitors
WO2025240847A1 (en)	2024-05-17	2025-11-20	Revolution Medicines, Inc.	Ras inhibitors
WO2025255438A1 (en)	2024-06-07	2025-12-11	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en)	2024-06-21	2025-12-26	Revolution Medicines, Inc.	Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en)	2024-06-28	2026-01-02	Revolution Medicines, Inc.	Ras inhibitors
WO2026015825A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Use of ras inhibitor for treating pancreatic cancer
WO2026015801A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015796A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015790A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3049207A1 (de) *	1980-12-27	1982-07-29	Dr. Karl Thomae Gmbh, 7950 Biberach	Neue trisubstituierte pyrimido (5,4-d) pyrimidine, ihre herstellung und ihre verwendung als arzneimittel
DE4325900A1 (de) *	1993-08-02	1995-02-09	Thomae Gmbh Dr K	Trisubstituierte Pyrimido [5,4-d] pyrimidine zur Modulation der Multidrugresistenz, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
TW414798B (en) *	1994-09-07	2000-12-11	Thomae Gmbh Dr K	Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation
DE4431867A1 (de) *	1994-09-07	1996-03-14	Thomae Gmbh Dr K	Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung

1996
- 1996-03-06 DE DE19608588A patent/DE19608588A1/de not_active Ceased
1997
- 1997-02-28 UY UY24474A patent/UY24474A1/es not_active Application Discontinuation
- 1997-03-03 TR TR1998/01755T patent/TR199801755T2/xx unknown
- 1997-03-03 EE EE9800278A patent/EE9800278A/xx unknown
- 1997-03-03 CN CN97192784A patent/CN1064362C/zh not_active Expired - Fee Related
- 1997-03-03 BR BR9707839A patent/BR9707839A/pt not_active Application Discontinuation
- 1997-03-03 AT AT97906152T patent/ATE252101T1/de not_active IP Right Cessation
- 1997-03-03 IL IL12534297A patent/IL125342A0/xx unknown
- 1997-03-03 KR KR1019980706935A patent/KR19990087504A/ko not_active Ceased
- 1997-03-03 HU HU9902049A patent/HUP9902049A3/hu not_active Application Discontinuation
- 1997-03-03 WO PCT/EP1997/001047 patent/WO1997032880A1/de not_active Ceased
- 1997-03-03 SK SK1208-98A patent/SK120898A3/sk unknown
- 1997-03-03 AU AU20945/97A patent/AU730376B2/en not_active Ceased
- 1997-03-03 DE DE59710864T patent/DE59710864D1/de not_active Expired - Fee Related
- 1997-03-03 NZ NZ331545A patent/NZ331545A/xx unknown
- 1997-03-03 RU RU98118380/04A patent/RU2195461C2/ru not_active IP Right Cessation
- 1997-03-03 CA CA002248720A patent/CA2248720A1/en not_active Abandoned
- 1997-03-03 EP EP97906152A patent/EP0888351B1/de not_active Expired - Lifetime
- 1997-03-03 JP JP9531440A patent/JP2000506151A/ja not_active Ceased
- 1997-03-03 PL PL97328719A patent/PL328719A1/xx unknown
- 1997-03-03 UA UA98105276A patent/UA54421C2/uk unknown
- 1997-03-03 CZ CZ982815A patent/CZ281598A3/cs unknown
- 1997-03-05 ZA ZA971887A patent/ZA971887B/xx unknown
- 1997-03-05 US US08/811,907 patent/US5821240A/en not_active Expired - Lifetime
- 1997-03-05 AR ARP970100873A patent/AR006108A1/es unknown
- 1997-03-06 TW TW086102755A patent/TW454008B/zh not_active IP Right Cessation
- 1997-03-06 CO CO97012277A patent/CO4650043A1/es unknown
1998
- 1998-08-31 MX MX9807073A patent/MX9807073A/es not_active IP Right Cessation
- 1998-09-04 NO NO19984082A patent/NO311522B1/no not_active IP Right Cessation
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Also Published As

Publication number	Publication date
TR199801755T2 (xx)	1998-12-21
DE19608588A1 (de)	1997-09-11
PL328719A1 (en)	1999-02-15
JP2000506151A (ja)	2000-05-23
CZ281598A3 (cs)	1999-02-17
CO4650043A1 (es)	1998-09-03
BR9707839A (pt)	1999-07-27
KR19990087504A (ko)	1999-12-27
EP0888351A1 (de)	1999-01-07
DE59710864D1 (de)	2003-11-20
HUP9902049A3 (en)	2000-03-28
ZA971887B (en)	1998-09-07
UY24474A1 (es)	2000-09-29
CA2248720A1 (en)	1997-09-12
CN1212694A (zh)	1999-03-31
NZ331545A (en)	2000-03-27
EE9800278A (et)	1999-02-15
CN1064362C (zh)	2001-04-11
HUP9902049A2 (hu)	1999-10-28
WO1997032880A1 (de)	1997-09-12
ATE252101T1 (de)	2003-11-15
SK120898A3 (en)	1999-02-11
NO984082D0 (no)	1998-09-04
AU730376B2 (en)	2001-03-08
AR006108A1 (es)	1999-08-11
IL125342A0 (en)	1999-03-12
US5821240A (en)	1998-10-13
NO984082L (no)	1998-09-04
UA54421C2 (uk)	2003-03-17
BG102789A (en)	1999-09-30
EP0888351B1 (de)	2003-10-15
TW454008B (en)	2001-09-11
RU2195461C2 (ru)	2002-12-27
MX9807073A (es)	1998-12-31
BG63163B1 (bg)	2001-05-31
AU2094597A (en)	1997-09-22
HK1018450A1 (en)	1999-12-24

Publication	Publication Date	Title
NO311522B1 (no)	2001-12-03	Pyrimido[5,4-d]pyrimidiner, legemiddel inneholdende disse forbindelser, deres anvendelse og fremgangsmåte for fremstillingderav
AU712072B2 (en)	1999-10-28	Pyrimido(5,4-d)pyrimidines, medicaments containing these compounds, their use and process for their production
AU710274B2 (en)	1999-09-16	4-amino-pyrimidine derivates, medicaments containing these compounds, their use and process for their production
CA2583737C (en)	2011-09-20	Compounds and compositions as protein kinase inhibitors
FI112947B (fi)	2004-02-13	Pyrimido[5,4-d]pyrimidiinejä, näitä yhdisteitä sisältävät lääkeaineet, niiden käyttö ja menetelmä niiden valmistamiseksi
US7709480B2 (en)	2010-05-04	Pyrimidine derivatives
EA009300B1 (ru)	2007-12-28	4-(n-фениламино)хиназолины/-хинолины в качестве ингибиторов тирозинкиназы
RS60501B1 (sr)	2020-08-31	Ligandi koji potenciraju bioaktivnost gonadotropina
RU2284325C2 (ru)	2006-09-27	Производные фенил-3-аминометил-хинолона-2 в качестве ингибиторов no-синтетазы, способ их получения, биологически активные соединения и фармацевтическая композиция на их основе
CA2361770A1 (en)	2000-09-21	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
KR100395271B1 (ko)	2003-11-28	피리미도[5,4-d]피리미딘및이를포함하는약제
MXPA98007154A (en)	1999-02-24	Pirimido [5,4-d] pyrimidinas, medicines containing these compounds, its employment and procedures for its preparation

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