HRP970641A2 - Fused bicyclic pyrimidine derivatives - Google Patents
Fused bicyclic pyrimidine derivativesInfo
- Publication number
- HRP970641A2 HRP970641A2 HR60/041,846A HRP970641A HRP970641A2 HR P970641 A2 HRP970641 A2 HR P970641A2 HR P970641 A HRP970641 A HR P970641A HR P970641 A2 HRP970641 A2 HR P970641A2
- Authority
- HR
- Croatia
- Prior art keywords
- phenyl
- alkyl
- pyrrolo
- cancer
- compound
- Prior art date
Links
- -1 bicyclic pyrimidine derivatives Chemical class 0.000 title claims description 31
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 120
- 238000000034 method Methods 0.000 claims description 61
- 201000010099 disease Diseases 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 206010028980 Neoplasm Diseases 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 35
- 241000124008 Mammalia Species 0.000 claims description 32
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 24
- 201000011510 cancer Diseases 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 230000003463 hyperproliferative effect Effects 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 210000003734 kidney Anatomy 0.000 claims description 13
- 210000002307 prostate Anatomy 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 210000000496 pancreas Anatomy 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 210000004072 lung Anatomy 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 210000000481 breast Anatomy 0.000 claims description 8
- 210000003739 neck Anatomy 0.000 claims description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 7
- 230000000340 anti-metabolite Effects 0.000 claims description 7
- 229940100197 antimetabolite Drugs 0.000 claims description 7
- 239000002256 antimetabolite Substances 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 210000003128 head Anatomy 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 6
- 108090000790 Enzymes Proteins 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 6
- 230000033115 angiogenesis Effects 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 206010020718 hyperplasia Diseases 0.000 claims description 6
- 238000002513 implantation Methods 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 210000002784 stomach Anatomy 0.000 claims description 6
- 210000003932 urinary bladder Anatomy 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 208000032612 Glial tumor Diseases 0.000 claims description 5
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 230000002280 anti-androgenic effect Effects 0.000 claims description 5
- 230000003388 anti-hormonal effect Effects 0.000 claims description 5
- 239000000051 antiandrogen Substances 0.000 claims description 5
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 5
- 210000001109 blastomere Anatomy 0.000 claims description 5
- 201000011066 hemangioma Diseases 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 210000001672 ovary Anatomy 0.000 claims description 5
- 201000002510 thyroid cancer Diseases 0.000 claims description 5
- 230000004862 vasculogenesis Effects 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- DVXIUBGLTXOANK-UHFFFAOYSA-N 1-[4-(3-methylanilino)pyrrolo[2,3-d]pyrimidin-7-yl]ethanone Chemical compound N1=CN=C2N(C(=O)C)C=CC2=C1NC1=CC=CC(C)=C1 DVXIUBGLTXOANK-UHFFFAOYSA-N 0.000 claims description 4
- VBXJEAKVYFNNDJ-UHFFFAOYSA-N 4-(6,7-dimethyl-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3CCC4=CC=C(C(=C43)C)C)=NC=NC2=C1 VBXJEAKVYFNNDJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 239000000367 immunologic factor Substances 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- BSEIRHPCQJAJNT-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-6-ol Chemical compound C1CC2=CC=C(Cl)C=C2N1C1=C(NC(O)=C2)C2=NC=N1 BSEIRHPCQJAJNT-UHFFFAOYSA-N 0.000 claims description 3
- CXAPZNBQPOKHKN-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3CCC4=CC=C(C=C43)Cl)=NC=NC2=C1 CXAPZNBQPOKHKN-UHFFFAOYSA-N 0.000 claims description 3
- ODEJVRVQXVOHIH-UHFFFAOYSA-N 6-bromo-n-(3-bromophenyl)-5-phenyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=12C(C=3C=CC=CC=3)=C(Br)NC2=NC=NC=1NC1=CC=CC(Br)=C1 ODEJVRVQXVOHIH-UHFFFAOYSA-N 0.000 claims description 3
- OZMLAELAHCCJQD-UHFFFAOYSA-N 7-(benzenesulfonyl)-n-(3-ethynylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC2=C(NC=3C=C(C=CC=3)C#C)N=CN=C2N1S(=O)(=O)C1=CC=CC=C1 OZMLAELAHCCJQD-UHFFFAOYSA-N 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 3
- 229940088598 enzyme Drugs 0.000 claims description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 239000012444 intercalating antibiotic Substances 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 230000000394 mitotic effect Effects 0.000 claims description 3
- CTSRNGUJBZEXEG-UHFFFAOYSA-N n-(1-benzothiophen-5-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=C2C(NC=3C=C4C=CSC4=CC=3)=NC=NC2=C1 CTSRNGUJBZEXEG-UHFFFAOYSA-N 0.000 claims description 3
- YGDFBBIYIJGILV-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-(3-nitrophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound [O-][N+](=O)C1=CC=CC(C=2C3=C(NC=4C=C(C=CC=4)C#C)N=CN=C3NC=2)=C1 YGDFBBIYIJGILV-UHFFFAOYSA-N 0.000 claims description 3
- DMOLWNVPSYNGLQ-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-(4-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C1=CNC2=NC=NC(NC=3C=C(C=CC=3)C#C)=C12 DMOLWNVPSYNGLQ-UHFFFAOYSA-N 0.000 claims description 3
- KGYYJCJOGOGJSS-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-(4-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1C1=CNC2=NC=NC(NC=3C=C(C=CC=3)C#C)=C12 KGYYJCJOGOGJSS-UHFFFAOYSA-N 0.000 claims description 3
- JRARLLWMUWCYCM-UHFFFAOYSA-N n-(3-ethynylphenyl)-5-thiophen-2-yl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C#CC1=CC=CC(NC=2C=3C(C=4SC=CC=4)=CNC=3N=CN=2)=C1 JRARLLWMUWCYCM-UHFFFAOYSA-N 0.000 claims description 3
- YFRSGDRAYOBDPX-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-(2-methoxyethyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(CCOC)C=CC2=C1NC1=CC=CC(C#C)=C1 YFRSGDRAYOBDPX-UHFFFAOYSA-N 0.000 claims description 3
- HGTHTZHDDWHETJ-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-(2-morpholin-4-ylethyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C#CC1=CC=CC(NC=2C=3C=CN(CCN4CCOCC4)C=3N=CN=2)=C1 HGTHTZHDDWHETJ-UHFFFAOYSA-N 0.000 claims description 3
- CQUCKWCAXJCZRR-UHFFFAOYSA-N n-(3-ethynylphenyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound C#CC1=CC=CC(NC=2C3=CC=NC=C3N=CN=2)=C1 CQUCKWCAXJCZRR-UHFFFAOYSA-N 0.000 claims description 3
- UIWSPJBKFSXXEY-UHFFFAOYSA-N n-(5-iodo-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-n-(3-methylphenyl)acetamide Chemical compound N=1C=NC=2NC=C(I)C=2C=1N(C(=O)C)C1=CC=CC(C)=C1 UIWSPJBKFSXXEY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- LDZCYEOEHIAAHI-UHFFFAOYSA-N 4-(4-bromo-7-methyl-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC(C(=CC=C2C)Br)=C2N1C1=C2C=C(C)N=CC2=NC=N1 LDZCYEOEHIAAHI-UHFFFAOYSA-N 0.000 claims description 2
- PSFWFZFQAFMWAW-UHFFFAOYSA-N 4-(5-chloro-6-fluoro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3C=4C=C(C(=CC=4CC3)Cl)F)=NC=NC2=C1 PSFWFZFQAFMWAW-UHFFFAOYSA-N 0.000 claims description 2
- PUSKXRAMJVBCGR-UHFFFAOYSA-N 4-(6-bromo-5-chloro-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3CCC=4C=C(C(=CC=43)Br)Cl)=NC=NC2=C1 PUSKXRAMJVBCGR-UHFFFAOYSA-N 0.000 claims description 2
- BGZUKOJRLCOJQL-UHFFFAOYSA-N 4-(6-bromo-5-fluoro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC(F)=C(Br)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 BGZUKOJRLCOJQL-UHFFFAOYSA-N 0.000 claims description 2
- FUYJBBSAMAELRK-UHFFFAOYSA-N 4-(6-bromo-7-methyl-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC=C(Br)C(C)=C2N1C1=C2C=C(C)N=CC2=NC=N1 FUYJBBSAMAELRK-UHFFFAOYSA-N 0.000 claims description 2
- PQTYWQWATNSLSN-UHFFFAOYSA-N 4-(6-chloro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC=C(Cl)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 PQTYWQWATNSLSN-UHFFFAOYSA-N 0.000 claims description 2
- DAWYJJHVSVSPNR-UHFFFAOYSA-N 4-(6-chloro-5-fluoro-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC(F)=C(Cl)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 DAWYJJHVSVSPNR-UHFFFAOYSA-N 0.000 claims description 2
- KNVRQKJXBXUQBZ-UHFFFAOYSA-N 4-(6-iodo-2,3-dihydroindol-1-yl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound C1CC2=CC=C(I)C=C2N1C1=C2C=C(C)N=CC2=NC=N1 KNVRQKJXBXUQBZ-UHFFFAOYSA-N 0.000 claims description 2
- VIFGQBSHDRRBMX-UHFFFAOYSA-N 4-(6-iodo-2,3-dihydroindol-1-yl)pyrido[3,4-d]pyrimidine Chemical compound N1=CC=C2C(N3CCC4=CC=C(C=C43)I)=NC=NC2=C1 VIFGQBSHDRRBMX-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- HDNMPTXODRTFCR-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-[2-(2-methoxyethoxy)ethyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(CCOCCOC)C=CC2=C1NC1=CC=CC(C#C)=C1 HDNMPTXODRTFCR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 7
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 101710183280 Topoisomerase Proteins 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000000203 mixture Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 239000000243 solution Substances 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- NNKQLUVBPJEUOR-UHFFFAOYSA-N 3-ethynylaniline Chemical group NC1=CC=CC(C#C)=C1 NNKQLUVBPJEUOR-UHFFFAOYSA-N 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
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- 239000000706 filtrate Substances 0.000 description 8
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
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- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
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- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 5
- CDJBDMNUBKPNQF-UHFFFAOYSA-N 7-(benzenesulfonyl)-4-chloro-5-iodopyrrolo[2,3-d]pyrimidine Chemical compound C1=C(I)C=2C(Cl)=NC=NC=2N1S(=O)(=O)C1=CC=CC=C1 CDJBDMNUBKPNQF-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
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- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
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- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- BWHOZHOGCMHOBV-BQYQJAHWSA-N trans-benzylideneacetone Chemical compound CC(=O)\C=C\C1=CC=CC=C1 BWHOZHOGCMHOBV-BQYQJAHWSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
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- 206010046766 uterine cancer Diseases 0.000 description 1
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- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
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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
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3186296P | 1996-11-27 | 1996-11-27 | |
| US4184697P | 1997-04-09 | 1997-04-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP970641A2 true HRP970641A2 (en) | 1998-10-31 |
Family
ID=26707706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/041,846A HRP970641A2 (en) | 1996-11-27 | 1997-11-26 | Fused bicyclic pyrimidine derivatives |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6413971B1 (fr) |
| EP (1) | EP0946554A1 (fr) |
| JP (1) | JP2000505109A (fr) |
| KR (1) | KR20000057228A (fr) |
| CN (1) | CN1237177A (fr) |
| AP (1) | AP9701146A0 (fr) |
| AR (1) | AR010740A1 (fr) |
| AU (1) | AU4718997A (fr) |
| BG (1) | BG103417A (fr) |
| BR (1) | BR9713552A (fr) |
| CA (1) | CA2272705C (fr) |
| CO (1) | CO4650037A1 (fr) |
| HN (1) | HN1997000146A (fr) |
| HR (1) | HRP970641A2 (fr) |
| ID (1) | ID18958A (fr) |
| IL (1) | IL129825A0 (fr) |
| IS (1) | IS5041A (fr) |
| MA (1) | MA26452A1 (fr) |
| NO (1) | NO992524D0 (fr) |
| OA (1) | OA11051A (fr) |
| PA (1) | PA8442001A1 (fr) |
| PE (1) | PE17299A1 (fr) |
| TN (1) | TNSN97192A1 (fr) |
| WO (1) | WO1998023613A1 (fr) |
Families Citing this family (91)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4275733B2 (ja) * | 1996-01-23 | 2009-06-10 | ノバルティス アクチエンゲゼルシャフト | ピロロピリミジンおよびその製造法 |
| BR9707495A (pt) | 1996-02-13 | 1999-07-27 | Zeneca Ltd | Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente |
| KR100489174B1 (ko) | 1996-03-05 | 2005-09-30 | 제네카-파마 소시에떼아노님 | 4-아닐리노퀴나졸린유도체 |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| KR100567649B1 (ko) | 1996-09-25 | 2006-04-05 | 아스트라제네카 유케이 리미티드 | 혈관 내피 성장 인자와 같은 성장 인자의 효과를 억제하는 퀴놀린 유도체 |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| ZA986729B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitors of tyrosine kinases |
| EP1005470B1 (fr) | 1997-08-22 | 2007-08-01 | AstraZeneca AB | Derives d'oxindolylquinazoline utiles comme inhibiteurs d'angiogenese |
| AU3951899A (en) * | 1998-06-19 | 2000-01-05 | Pfizer Products Inc. | Pyrrolo(2,3-d)pyrimidine compounds |
| PA8474101A1 (es) * | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| EP1226136B1 (fr) | 1999-10-19 | 2004-12-29 | Merck & Co., Inc. | Inhibiteurs de tyrosine kinases |
| US6794393B1 (en) | 1999-10-19 | 2004-09-21 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| EP1676845B1 (fr) | 1999-11-05 | 2008-06-11 | AstraZeneca AB | Nouveaux dérivés de type quinazoline |
| JP4078074B2 (ja) | 1999-12-10 | 2008-04-23 | ファイザー・プロダクツ・インク | ピロロ［２，３−ｄ］ピリミジン化合物 |
| ES2245955T3 (es) | 1999-12-21 | 2006-02-01 | Sugen, Inc. | 7-aza-indolin-2-onas 4-sustituidas y su utilizacion como inhibidores de proteina-quinasa. |
| US6420382B2 (en) | 2000-02-25 | 2002-07-16 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6313138B1 (en) | 2000-02-25 | 2001-11-06 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6608053B2 (en) | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| ES2223827T3 (es) | 2000-06-06 | 2005-03-01 | Pfizer Products Inc. | Derivados de tiofeno utiles como agentes anticancerigenos. |
| CN100351253C (zh) | 2000-06-26 | 2007-11-28 | 辉瑞产品公司 | 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物 |
| WO2002032861A2 (fr) | 2000-10-17 | 2002-04-25 | Merck & Co., Inc. | Sels oralement actifs a activite tyrosine kinase |
| DE60134679D1 (de) | 2000-10-20 | 2008-08-14 | Eisai R&D Man Co Ltd | Stickstoff enthaltende aromatische Heterozyklen |
| ES2372028T3 (es) | 2000-10-23 | 2012-01-13 | Glaxosmithkline Llc | Nuevo compuesto de 8h-pirido[2,3-d]pirimidin-7-ona trisustituida para el tratamiento de enfermedades mediadas por la csbp/p38 quinasa. |
| AR035885A1 (es) | 2001-05-14 | 2004-07-21 | Novartis Ag | Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica |
| US7301023B2 (en) | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| WO2003000194A2 (fr) | 2001-06-21 | 2003-01-03 | Pfizer Inc. | Derives bicycliques de pyridine et de pyrimidine utiles en tant qu'agents anticancereux |
| GB0115393D0 (en) * | 2001-06-23 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| US7169788B2 (en) | 2001-10-30 | 2007-01-30 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| EP1471910A2 (fr) * | 2002-01-17 | 2004-11-03 | Neurogen Corporation | Analogues de quinazoline-4-ylamine substitues comme modulateurs de receptors de la capsaicin |
| BR0308162A (pt) | 2002-03-01 | 2004-12-07 | Pfizer | Derivados de indolil-uréia de tienopiridinas úteis como agentes antiangiogênicos e métodos para o seu uso |
| UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
| KR20050086784A (ko) | 2002-11-26 | 2005-08-30 | 화이자 프로덕츠 인크. | 이식 거부반응의 치료 방법 |
| US7432275B2 (en) * | 2002-12-13 | 2008-10-07 | Neurogen Corporation | Carboxylic acid, phosphate or phosphonate substituted quinazolin-4-ylamine analogues as capsaicin receptor modulators |
| US7329664B2 (en) * | 2003-07-16 | 2008-02-12 | Neurogen Corporation | Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues |
| ATE412655T1 (de) | 2003-08-29 | 2008-11-15 | Pfizer | Als neue antiangiogene mittel geeignete thienopyridinphenylacetamide und derivate davon |
| AU2004270740A1 (en) * | 2003-09-09 | 2005-03-17 | Neurogen Corporation | 4 - heterobicyclyamino - substituted quinazolines and analogues therof as capsaicin - antagonists |
| JP4303726B2 (ja) | 2003-11-11 | 2009-07-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ウレア誘導体およびその製造方法 |
| JP2007511596A (ja) | 2003-11-17 | 2007-05-10 | ファイザー・プロダクツ・インク | 癌の治療において有用なピロロピリミジン化合物 |
| CN1890234A (zh) | 2003-12-23 | 2007-01-03 | 辉瑞大药厂 | 新颖的喹啉衍生物 |
| CA2566160C (fr) | 2004-05-27 | 2011-01-18 | Pfizer Products Inc. | Derives pyrrolopyrimidiniques convenant au traitement du cancer |
| ZA200610669B (en) * | 2004-06-02 | 2008-06-25 | Takeda Pharmaceutical | Fused heterocyclic compound |
| WO2005118588A1 (fr) * | 2004-06-02 | 2005-12-15 | Takeda Pharmaceutical Company Limited | Composé heterocyclique fusionné |
| US8969379B2 (en) | 2004-09-17 | 2015-03-03 | Eisai R&D Management Co., Ltd. | Pharmaceutical compositions of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7=methoxy-6-quinolinecarboxide |
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-
1997
- 1997-11-05 CA CA002272705A patent/CA2272705C/fr not_active Expired - Fee Related
- 1997-11-05 KR KR1019990704587A patent/KR20000057228A/ko not_active Application Discontinuation
- 1997-11-05 EP EP97909525A patent/EP0946554A1/fr not_active Ceased
- 1997-11-05 CN CN97199662A patent/CN1237177A/zh active Pending
- 1997-11-05 BR BR9713552-6A patent/BR9713552A/pt unknown
- 1997-11-05 WO PCT/IB1997/001393 patent/WO1998023613A1/fr not_active Application Discontinuation
- 1997-11-05 AU AU47189/97A patent/AU4718997A/en not_active Abandoned
- 1997-11-05 IL IL12982597A patent/IL129825A0/xx unknown
- 1997-11-05 US US09/308,602 patent/US6413971B1/en not_active Expired - Fee Related
- 1997-11-05 JP JP10524465A patent/JP2000505109A/ja active Pending
- 1997-11-07 HN HN1997000146A patent/HN1997000146A/es unknown
- 1997-11-20 PE PE1997001057A patent/PE17299A1/es not_active Application Discontinuation
- 1997-11-20 AP APAP/P/1997/001146A patent/AP9701146A0/en unknown
- 1997-11-25 AR ARP970105506A patent/AR010740A1/es unknown
- 1997-11-25 CO CO97068959A patent/CO4650037A1/es unknown
- 1997-11-26 PA PA19978442001A patent/PA8442001A1/es unknown
- 1997-11-26 ID IDP973768A patent/ID18958A/id unknown
- 1997-11-26 TN TNTNSN97192A patent/TNSN97192A1/fr unknown
- 1997-11-26 HR HR60/041,846A patent/HRP970641A2/hr not_active Application Discontinuation
- 1997-11-26 MA MA24878A patent/MA26452A1/fr unknown
-
1999
- 1999-04-30 IS IS5041A patent/IS5041A/is unknown
- 1999-05-20 BG BG103417A patent/BG103417A/xx unknown
- 1999-05-24 OA OA9900107A patent/OA11051A/en unknown
- 1999-05-26 NO NO992524A patent/NO992524D0/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TNSN97192A1 (fr) | 2005-03-15 |
| AP9701146A0 (en) | 1998-01-31 |
| IS5041A (is) | 1999-04-30 |
| PA8442001A1 (es) | 2000-05-24 |
| ID18958A (id) | 1998-05-28 |
| JP2000505109A (ja) | 2000-04-25 |
| OA11051A (en) | 2003-03-07 |
| US6413971B1 (en) | 2002-07-02 |
| AU4718997A (en) | 1998-06-22 |
| PE17299A1 (es) | 1999-02-19 |
| NO992524L (no) | 1999-05-26 |
| CN1237177A (zh) | 1999-12-01 |
| BG103417A (en) | 2000-06-30 |
| CO4650037A1 (es) | 1998-09-03 |
| NO992524D0 (no) | 1999-05-26 |
| IL129825A0 (en) | 2000-02-29 |
| US20020045630A1 (en) | 2002-04-18 |
| EP0946554A1 (fr) | 1999-10-06 |
| HN1997000146A (es) | 1998-02-26 |
| CA2272705C (fr) | 2003-03-18 |
| KR20000057228A (ko) | 2000-09-15 |
| CA2272705A1 (fr) | 1998-06-04 |
| BR9713552A (pt) | 2000-01-25 |
| MA26452A1 (fr) | 2004-12-20 |
| WO1998023613A1 (fr) | 1998-06-04 |
| AR010740A1 (es) | 2000-07-12 |
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