CA2303487A1 - Antagonistes du recepteur de la vitronectine - Google Patents
Antagonistes du recepteur de la vitronectine Download PDFInfo
- Publication number
- CA2303487A1 CA2303487A1 CA002303487A CA2303487A CA2303487A1 CA 2303487 A1 CA2303487 A1 CA 2303487A1 CA 002303487 A CA002303487 A CA 002303487A CA 2303487 A CA2303487 A CA 2303487A CA 2303487 A1 CA2303487 A1 CA 2303487A1
- Authority
- CA
- Canada
- Prior art keywords
- dihydro
- dibenzo
- cycloheptene
- propyloxy
- ylamino
- Prior art date
- 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.)
- Abandoned
Links
- 102100022337 Integrin alpha-V Human genes 0.000 title abstract description 22
- 108010048673 Vitronectin Receptors Proteins 0.000 title abstract description 22
- 239000002464 receptor antagonist Substances 0.000 title abstract description 3
- 229940044551 receptor antagonist Drugs 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 301
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 17
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 124
- 238000000034 method Methods 0.000 claims description 98
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 22
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- 229940034982 antineoplastic agent Drugs 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 208000006386 Bone Resorption Diseases 0.000 claims description 12
- 230000024279 bone resorption Effects 0.000 claims description 12
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 11
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
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- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 206010027476 Metastases Diseases 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical group C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 6
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- 206010061218 Inflammation Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
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- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 5
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- HODBWQCCKYDYPY-OAQYLSRUSA-N 2-[(6r)-2-[3-(pyridin-2-ylamino)propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound C([C@@H](C1=CC=CC=C1CC1=C2)CC(=O)O)C1=CC=C2OCCCNC1=CC=CC=N1 HODBWQCCKYDYPY-OAQYLSRUSA-N 0.000 claims 1
- HEPGRAXGZMLPDH-FQEVSTJZSA-N 2-[(6s)-2-[2-[6-(methylamino)pyridin-2-yl]ethoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound CNC1=CC=CC(CCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=N1 HEPGRAXGZMLPDH-FQEVSTJZSA-N 0.000 claims 1
- UOZHWCRUZCASIR-NRFANRHFSA-N 2-[(6s)-2-[3-(2-aminopyridin-4-yl)propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound C1=NC(N)=CC(CCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 UOZHWCRUZCASIR-NRFANRHFSA-N 0.000 claims 1
- HODBWQCCKYDYPY-NRFANRHFSA-N 2-[(6s)-2-[3-(pyridin-2-ylamino)propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound C([C@H](C1=CC=CC=C1CC1=C2)CC(=O)O)C1=CC=C2OCCCNC1=CC=CC=N1 HODBWQCCKYDYPY-NRFANRHFSA-N 0.000 claims 1
- SOILSVKSKBGUFR-FQEVSTJZSA-N 2-[(6s)-2-[3-[(4-aminopyridin-2-yl)amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound NC1=CC=NC(NCCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 SOILSVKSKBGUFR-FQEVSTJZSA-N 0.000 claims 1
- WCDIYCAFNSQHFX-FQEVSTJZSA-N 2-[(6s)-2-[3-[(4-chloropyridin-2-yl)amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound C([C@H](C1=CC=CC=C1CC1=C2)CC(=O)O)C1=CC=C2OCCCNC1=CC(Cl)=CC=N1 WCDIYCAFNSQHFX-FQEVSTJZSA-N 0.000 claims 1
- OSJLLSUUWUGISI-QFIPXVFZSA-N 2-[(6s)-2-[3-[(4-ethoxypyridin-2-yl)amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound CCOC1=CC=NC(NCCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 OSJLLSUUWUGISI-QFIPXVFZSA-N 0.000 claims 1
- WYBWIOJIELCLSD-QFIPXVFZSA-N 2-[(6s)-2-[3-[(4-methylpyridin-2-yl)amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound CC1=CC=NC(NCCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 WYBWIOJIELCLSD-QFIPXVFZSA-N 0.000 claims 1
- MKKARCNIQGVIES-QHCPKHFHSA-N 2-[(6s)-2-[3-[(4-propan-2-yloxypyridin-2-yl)amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound CC(C)OC1=CC=NC(NCCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 MKKARCNIQGVIES-QHCPKHFHSA-N 0.000 claims 1
- RDDVTQJLWBWBKZ-QFIPXVFZSA-N 2-[(6s)-2-[3-[[4-(dimethylamino)pyridin-2-yl]amino]propoxy]-6,11-dihydro-5h-dibenzo[3,2-[7]annulen-6-yl]acetic acid Chemical compound CN(C)C1=CC=NC(NCCCOC=2C=C3CC4=CC=CC=C4[C@H](CC(O)=O)CC3=CC=2)=C1 RDDVTQJLWBWBKZ-QFIPXVFZSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 200
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
- 239000000243 solution Substances 0.000 description 124
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 113
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- 229910001868 water Inorganic materials 0.000 description 87
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- 239000000203 mixture Substances 0.000 description 86
- 229960000583 acetic acid Drugs 0.000 description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 235000019439 ethyl acetate Nutrition 0.000 description 76
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 49
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- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- IBKQNYOMAJASCZ-UHFFFAOYSA-M sodium 2-chloro-4-methylpyridine nitrite Chemical compound N(=O)[O-].[Na+].ClC1=NC=CC(=C1)C IBKQNYOMAJASCZ-UHFFFAOYSA-M 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
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- 230000009870 specific binding Effects 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
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- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
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- 230000009466 transformation Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/48—Nitrogen atoms not forming part of a nitro radical with acyclic hydrocarbon or substituted acyclic hydrocarbon radicals, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/14—Nitrogen atoms not forming part of a nitro radical with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/14—[b,f]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
L'invention a trait à des composés représentés par la formule (I) qui constituent des antagonistes du récepteur de la vitronectine et sont utiles dans le traitement de l'ostéoporose, ou à un sel pharmaceutiquement acceptable de ces composés. Dans la formule, A est CH¿2? ou O; R?1¿ est H, halo ou alkyle en C¿1-6?; R?2¿ est H, alkyle en C¿1-6? ou CH¿2?NR"R"; X est O ou CH¿2?; Y est (a), (b), (c), (d), (e), (f) ou (g); G est NR", S ou O; R' est H, alkyle en C¿1-6?, OC¿1-6?alkyle, SC¿1-6?alkyle, NR"R" ou halo; chaque R" est indépendamment H ou alkyle en C¿1-6?, et s est 0, 1 ou 2.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5934297P | 1997-09-19 | 1997-09-19 | |
| US60/059,342 | 1997-09-19 | ||
| US6343897P | 1997-10-29 | 1997-10-29 | |
| US60/063,438 | 1997-10-29 | ||
| PCT/US1998/019466 WO1999015508A1 (fr) | 1997-09-19 | 1998-09-18 | Antagonistes du recepteur de la vitronectine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2303487A1 true CA2303487A1 (fr) | 1999-04-01 |
Family
ID=26738652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002303487A Abandoned CA2303487A1 (fr) | 1997-09-19 | 1998-09-18 | Antagonistes du recepteur de la vitronectine |
Country Status (26)
| Country | Link |
|---|---|
| EP (1) | EP1025090A4 (fr) |
| JP (1) | JP2001517658A (fr) |
| KR (1) | KR20010024141A (fr) |
| CN (1) | CN1278250A (fr) |
| AP (1) | AP2000001766A0 (fr) |
| AR (1) | AR015446A1 (fr) |
| AU (1) | AU738433B2 (fr) |
| BG (1) | BG104314A (fr) |
| BR (1) | BR9812340A (fr) |
| CA (1) | CA2303487A1 (fr) |
| CO (1) | CO5011087A1 (fr) |
| DZ (1) | DZ2609A1 (fr) |
| EA (1) | EA200000336A1 (fr) |
| HU (1) | HUP0003641A3 (fr) |
| ID (1) | ID24162A (fr) |
| IL (1) | IL135028A0 (fr) |
| MA (1) | MA26547A1 (fr) |
| NO (1) | NO20001407L (fr) |
| NZ (1) | NZ503389A (fr) |
| OA (1) | OA11341A (fr) |
| PE (1) | PE122699A1 (fr) |
| PL (1) | PL339381A1 (fr) |
| SK (1) | SK4082000A3 (fr) |
| TR (1) | TR200000721T2 (fr) |
| TW (1) | TW513303B (fr) |
| WO (1) | WO1999015508A1 (fr) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CO4920232A1 (es) * | 1997-01-08 | 2000-05-29 | Smithkline Beecham Corp | Acidos aceticos dibenzo [a,d] cicloheptano con actividad antagonista del receptor de vitronectin |
| AU747503B2 (en) | 1999-02-03 | 2002-05-16 | Merck & Co., Inc. | Benzazepine derivatives as alpha-V integrin receptor antagonists |
| DE19936780A1 (de) | 1999-08-09 | 2001-02-15 | Basf Ag | Neue Antagonisten von Integrinrezeptoren |
| US6881736B1 (en) | 1999-09-07 | 2005-04-19 | Smithkline Beecham Corporation | Vitronectin receptor antagonists |
| EG24179A (en) * | 1999-09-07 | 2008-09-28 | Smithkline Beecham Corp | Vitronectin receptor antagonists |
| US6514964B1 (en) | 1999-09-27 | 2003-02-04 | Amgen Inc. | Fused cycloheptane and fused azacycloheptane compounds and their methods of use |
| FR2806082B1 (fr) * | 2000-03-07 | 2002-05-17 | Adir | Nouveaux composes bicycliques antagonistes des recepteurs de la vitronectine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6720315B2 (en) | 2000-06-15 | 2004-04-13 | Pharmacia Corporation | Dihydrostilbene alkanoic acid derivatives |
| ATE320258T1 (de) * | 2000-10-24 | 2006-04-15 | Merck & Co Inc | Dibenzoxazepin-alpha-v-integrin- rezeptorantagonist |
| EP1381384B1 (fr) | 2001-04-24 | 2011-05-25 | Merck Patent GmbH | POLYTHERAPIE A BASE D'AGENTS ANTIANGIOGENIQUES ET DE FACTEUR DE NECROSE TUMORALE TNFalpha |
| GB0215867D0 (en) * | 2002-07-09 | 2002-08-14 | Glaxosmithkline Spa | Novel method and compounds |
| US20040224986A1 (en) | 2002-08-16 | 2004-11-11 | Bart De Corte | Piperidinyl targeting compounds that selectively bind integrins |
| UA87854C2 (en) | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
| EP1973569B1 (fr) | 2006-01-18 | 2013-05-22 | Merck Patent GmbH | Traitement specifique utilisant des ligands de integrine destine a traiter un cancer |
| JP2010516645A (ja) | 2007-01-18 | 2010-05-20 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌を治療するためのインテグリンリガンドを用いる特異的療法および薬剤 |
| US20120130146A1 (en) | 2009-05-25 | 2012-05-24 | Merck Patent Gmbh | Continuous administration of cilengitide in cancer treatments |
| ES2864079T3 (es) | 2014-05-30 | 2021-10-13 | Pfizer | Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos |
| WO2023275715A1 (fr) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Métabolites de modulateurs sélectifs du récepteur des androgènes |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH450398A (de) * | 1964-02-18 | 1968-01-31 | Hoffmann La Roche | Verfahren zur Herstellung von Dibenzocycloheptatrienverbindungen |
| US3335148A (en) * | 1966-02-17 | 1967-08-08 | Lilly Co Eli | 9(3-pyridyl)derivative of fluorene, 9-fluorenol, xanthene, 9-xanthenol and the corresponding nonphytotoxic acid addition salts thereof |
| US5698551A (en) * | 1995-04-07 | 1997-12-16 | Novo Nordisk A/S | Heterocyclic compounds |
| EP0910563B1 (fr) * | 1995-06-29 | 2003-05-02 | Smithkline Beecham Corporation | Antagonistes du recepteur de l'integrine |
| US5659033A (en) * | 1995-09-13 | 1997-08-19 | Neurogen Corporation | N-aminoalkylfluorenecarboxamides; a new class of dopamine receptor subtype specific ligands |
| EP0946180A4 (fr) * | 1996-10-07 | 2003-07-23 | Smithkline Beecham Corp | Procede de stimulation de la formation osseuse |
| CO4920232A1 (es) * | 1997-01-08 | 2000-05-29 | Smithkline Beecham Corp | Acidos aceticos dibenzo [a,d] cicloheptano con actividad antagonista del receptor de vitronectin |
-
1998
- 1998-09-16 AR ARP980104604A patent/AR015446A1/es not_active Application Discontinuation
- 1998-09-16 PE PE1998000881A patent/PE122699A1/es not_active Application Discontinuation
- 1998-09-16 DZ DZ980219A patent/DZ2609A1/fr active
- 1998-09-18 KR KR1020007002901A patent/KR20010024141A/ko not_active Ceased
- 1998-09-18 SK SK408-2000A patent/SK4082000A3/sk unknown
- 1998-09-18 WO PCT/US1998/019466 patent/WO1999015508A1/fr not_active Ceased
- 1998-09-18 CA CA002303487A patent/CA2303487A1/fr not_active Abandoned
- 1998-09-18 TR TR2000/00721T patent/TR200000721T2/xx unknown
- 1998-09-18 HU HU0003641A patent/HUP0003641A3/hu unknown
- 1998-09-18 AU AU93972/98A patent/AU738433B2/en not_active Ceased
- 1998-09-18 CO CO98053986A patent/CO5011087A1/es unknown
- 1998-09-18 PL PL98339381A patent/PL339381A1/xx unknown
- 1998-09-18 ID IDW20000468A patent/ID24162A/id unknown
- 1998-09-18 AP APAP/P/2000/001766A patent/AP2000001766A0/en unknown
- 1998-09-18 IL IL13502898A patent/IL135028A0/xx unknown
- 1998-09-18 NZ NZ503389A patent/NZ503389A/en not_active IP Right Cessation
- 1998-09-18 EA EA200000336A patent/EA200000336A1/ru unknown
- 1998-09-18 EP EP98947116A patent/EP1025090A4/fr not_active Withdrawn
- 1998-09-18 JP JP2000512816A patent/JP2001517658A/ja not_active Withdrawn
- 1998-09-18 CN CN98810811A patent/CN1278250A/zh active Pending
- 1998-09-18 BR BR9812340-8A patent/BR9812340A/pt not_active Application Discontinuation
- 1998-09-18 MA MA25266A patent/MA26547A1/fr unknown
- 1998-09-23 TW TW087115535A patent/TW513303B/zh not_active IP Right Cessation
-
2000
- 2000-03-16 OA OA1200000079A patent/OA11341A/en unknown
- 2000-03-17 NO NO20001407A patent/NO20001407L/no not_active Application Discontinuation
- 2000-04-07 BG BG104314A patent/BG104314A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MA26547A1 (fr) | 2004-12-20 |
| EP1025090A1 (fr) | 2000-08-09 |
| EP1025090A4 (fr) | 2000-11-08 |
| CO5011087A1 (es) | 2001-02-28 |
| ID24162A (id) | 2000-07-13 |
| SK4082000A3 (en) | 2000-09-12 |
| TW513303B (en) | 2002-12-11 |
| NO20001407D0 (no) | 2000-03-17 |
| BG104314A (en) | 2001-01-31 |
| PE122699A1 (es) | 2000-02-12 |
| AP2000001766A0 (en) | 1998-09-18 |
| EA200000336A1 (ru) | 2000-10-30 |
| AR015446A1 (es) | 2001-05-02 |
| OA11341A (en) | 2003-12-10 |
| AU9397298A (en) | 1999-04-12 |
| DZ2609A1 (fr) | 2003-03-01 |
| JP2001517658A (ja) | 2001-10-09 |
| IL135028A0 (en) | 2001-05-20 |
| NZ503389A (en) | 2002-03-28 |
| NO20001407L (no) | 2000-03-17 |
| BR9812340A (pt) | 2001-12-18 |
| WO1999015508A1 (fr) | 1999-04-01 |
| KR20010024141A (ko) | 2001-03-26 |
| AU738433B2 (en) | 2001-09-20 |
| TR200000721T2 (tr) | 2000-11-21 |
| CN1278250A (zh) | 2000-12-27 |
| HUP0003641A2 (en) | 2001-03-28 |
| HUP0003641A3 (en) | 2002-10-28 |
| PL339381A1 (en) | 2000-12-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |