NO311671B1 - Meta-guanidin-, urea-, tiourea- eller azacykliske aminobenzosyrederivater som integrin-antagonister samt preparaterinneholdende forbindelsene - Google Patents
Meta-guanidin-, urea-, tiourea- eller azacykliske aminobenzosyrederivater som integrin-antagonister samt preparaterinneholdende forbindelsene Download PDFInfo
- Publication number
- NO311671B1 NO311671B1 NO19980817A NO980817A NO311671B1 NO 311671 B1 NO311671 B1 NO 311671B1 NO 19980817 A NO19980817 A NO 19980817A NO 980817 A NO980817 A NO 980817A NO 311671 B1 NO311671 B1 NO 311671B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- carbonyl
- acetyl
- phenyl
- aminoiminomethyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 164
- 238000002360 preparation method Methods 0.000 title claims description 126
- 239000005557 antagonist Substances 0.000 title abstract description 10
- 108010044426 integrins Proteins 0.000 title description 22
- 102000006495 integrins Human genes 0.000 title description 22
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title description 10
- 239000004202 carbamide Substances 0.000 title description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 title description 4
- 150000005417 aminobenzoic acid derivatives Chemical class 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 1626
- -1 tetrahydropyrimidyl Chemical group 0.000 claims description 622
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 463
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 458
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 438
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 146
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 72
- 239000002253 acid Substances 0.000 claims description 70
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 50
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 48
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 17
- 239000005711 Benzoic acid Substances 0.000 claims description 16
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 16
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 15
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 13
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 235000010233 benzoic acid Nutrition 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- OYJGEOAXBALSMM-UHFFFAOYSA-N 2,3-dihydro-1,3-thiazole Chemical compound C1NC=CS1 OYJGEOAXBALSMM-UHFFFAOYSA-N 0.000 claims description 7
- NWWJFMCCTZLKNT-UHFFFAOYSA-N 3,4-dihydro-2h-thiazine Chemical compound C1CC=CSN1 NWWJFMCCTZLKNT-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000468 ketone group Chemical group 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 5
- LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 claims description 5
- 229930194542 Keto Natural products 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- KSLYEQUQAKOOQD-UHFFFAOYSA-N 3-[3-[[3-(hydrazinylmethylideneamino)benzoyl]amino]-2-oxopyrrolidin-1-yl]propanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NC2C(N(CCC(O)=O)CC2)=O)=C1 KSLYEQUQAKOOQD-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- JNKRWRVTDDWVRX-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-4-(2-hydroxyethylamino)-4-oxobutanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NCC(=O)NC(CC(O)=O)C(=O)NCCO)=C1 JNKRWRVTDDWVRX-UHFFFAOYSA-N 0.000 claims description 3
- XTEOSTSZMZPDRX-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-5-(4-methylphenyl)sulfanylpentanoic acid Chemical compound C1=CC(C)=CC=C1SCCC(CC(O)=O)NC(=O)CNC(=O)C1=CC=CC(N=CNN)=C1 XTEOSTSZMZPDRX-UHFFFAOYSA-N 0.000 claims description 3
- DQPSXCVSKMRESK-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-5-(4-methylphenyl)sulfonylpentanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)CCC(CC(O)=O)NC(=O)CNC(=O)C1=CC=CC(N=CNN)=C1 DQPSXCVSKMRESK-UHFFFAOYSA-N 0.000 claims description 3
- XBKZMTMPQSFFEL-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]pentanedioic acid Chemical compound NNC=NC1=CC=CC(C(=O)NCC(=O)NC(CC(O)=O)CC(O)=O)=C1 XBKZMTMPQSFFEL-UHFFFAOYSA-N 0.000 claims description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 150000005215 alkyl ethers Chemical class 0.000 claims description 3
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- ZTZLNVAKDQJMAJ-UHFFFAOYSA-N methyl 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-4-[(4-methylphenyl)sulfonylamino]butanoate Chemical compound C=1C=CC(N=CNN)=CC=1C(=O)NCC(=O)NC(CC(=O)OC)CNS(=O)(=O)C1=CC=C(C)C=C1 ZTZLNVAKDQJMAJ-UHFFFAOYSA-N 0.000 claims description 2
- OTNYEDZLGUYATO-UHFFFAOYSA-N methyl 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-5-(4-methylphenyl)sulfanylpentanoate Chemical compound C=1C=CC(N=CNN)=CC=1C(=O)NCC(=O)NC(CC(=O)OC)CCSC1=CC=C(C)C=C1 OTNYEDZLGUYATO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 41
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 8
- WDGXIUUWINKTGP-UHFFFAOYSA-N 3-(3-pyridinyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CN=C1 WDGXIUUWINKTGP-UHFFFAOYSA-N 0.000 claims 7
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims 6
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims 6
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 5
- 235000019260 propionic acid Nutrition 0.000 claims 5
- LAOMDZFORKFNPV-UHFFFAOYSA-N 3-(2-aminophenyl)propanoic acid Chemical compound NC1=CC=CC=C1CCC(O)=O LAOMDZFORKFNPV-UHFFFAOYSA-N 0.000 claims 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 4
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000001425 triazolyl group Chemical group 0.000 claims 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims 3
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims 2
- AORNGRSGHHDCBG-UHFFFAOYSA-N 3-[[2-[[3-(benzylcarbamoylamino)benzoyl]amino]acetyl]amino]propanoic acid Chemical compound OC(=O)CCNC(=O)CNC(=O)C1=CC=CC(NC(=O)NCC=2C=CC=CC=2)=C1 AORNGRSGHHDCBG-UHFFFAOYSA-N 0.000 claims 2
- ITKZILJRBUJZGC-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-4-methylpentanoic acid Chemical compound OC(=O)CC(C(C)C)NC(=O)CNC(=O)C1=CC=CC(NC=NN)=C1 ITKZILJRBUJZGC-UHFFFAOYSA-N 0.000 claims 2
- BQCIKRSJKFOLMT-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]pentanoic acid Chemical compound OC(=O)CC(CC)NC(=O)CNC(=O)C1=CC=CC(N=CNN)=C1 BQCIKRSJKFOLMT-UHFFFAOYSA-N 0.000 claims 2
- KWIFIAXUSVMKPO-UHFFFAOYSA-N 4,4,4-trifluoro-3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]butanoic acid Chemical compound NNC=NC1=CC=CC(C(=O)NCC(=O)NC(CC(O)=O)C(F)(F)F)=C1 KWIFIAXUSVMKPO-UHFFFAOYSA-N 0.000 claims 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 2
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims 2
- IIIBLNGKQJHTHM-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]butanoate Chemical compound CCOC(=O)CC(C(F)(F)F)NC(=O)CNC(=O)C1=CC=CC(N=CNN)=C1 IIIBLNGKQJHTHM-UHFFFAOYSA-N 0.000 claims 2
- JTMFNTIKWZIXPJ-UHFFFAOYSA-N ethyl 5-(3,5-dichloroanilino)-3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-5-oxopentanoate Chemical compound C=1C=CC(N=CNN)=CC=1C(=O)NCC(=O)NC(CC(=O)OCC)CC(=O)NC1=CC(Cl)=CC(Cl)=C1 JTMFNTIKWZIXPJ-UHFFFAOYSA-N 0.000 claims 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-L glutarate(2-) Chemical compound [O-]C(=O)CCCC([O-])=O JFCQEDHGNNZCLN-UHFFFAOYSA-L 0.000 claims 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 2
- 229960002248 meradimate Drugs 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- UIYJGLLTSVRSBM-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=C2OCOC2=C1 UIYJGLLTSVRSBM-UHFFFAOYSA-N 0.000 claims 1
- RSCSQNQHINMHDE-UHFFFAOYSA-N 3-(1-benzofuran-2-yl)propanoic acid Chemical compound C1=CC=C2OC(CCC(=O)O)=CC2=C1 RSCSQNQHINMHDE-UHFFFAOYSA-N 0.000 claims 1
- QJOCBCMKVRKWLM-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(Cl)=C1Cl QJOCBCMKVRKWLM-UHFFFAOYSA-N 0.000 claims 1
- KZMDFTFGWIVSNQ-UHFFFAOYSA-N 3-(2-chlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1Cl KZMDFTFGWIVSNQ-UHFFFAOYSA-N 0.000 claims 1
- CJBDUOMQLFKVQC-UHFFFAOYSA-N 3-(2-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1O CJBDUOMQLFKVQC-UHFFFAOYSA-N 0.000 claims 1
- GQICJNXGCGRFBA-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC(Cl)=CC(Cl)=C1 GQICJNXGCGRFBA-UHFFFAOYSA-N 0.000 claims 1
- VWXVTHDQAOAENP-UHFFFAOYSA-N 3-(3-methylphenyl)propanoic acid Chemical compound CC1=CC=CC(CCC(O)=O)=C1 VWXVTHDQAOAENP-UHFFFAOYSA-N 0.000 claims 1
- BEIDQWZVANMVNC-UHFFFAOYSA-N 3-[2,3-bis(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC(C(F)(F)F)=C1C(F)(F)F BEIDQWZVANMVNC-UHFFFAOYSA-N 0.000 claims 1
- WRSOKQANINWHRE-UHFFFAOYSA-N 3-[2-[[2-[[3-[[n,n'-bis(ethoxycarbonyl)carbamimidoyl]amino]benzoyl]amino]acetyl]amino]-3,5-dichlorophenyl]propanoic acid Chemical compound CCOC(=O)NC(=NC(=O)OCC)NC1=CC=CC(C(=O)NCC(=O)NC=2C(=CC(Cl)=CC=2Cl)CCC(O)=O)=C1 WRSOKQANINWHRE-UHFFFAOYSA-N 0.000 claims 1
- UVSKTYFODPNNBW-UHFFFAOYSA-N 3-[3,5-dichloro-2-[[2-[[3-[(N-ethyl-N'-methylcarbamimidoyl)amino]benzoyl]amino]acetyl]amino]phenyl]propanoic acid Chemical compound CCNC(=NC)NC1=CC=CC(C(=O)NCC(=O)NC=2C(=CC(Cl)=CC=2Cl)CCC(O)=O)=C1 UVSKTYFODPNNBW-UHFFFAOYSA-N 0.000 claims 1
- LZPNSKVTBKQVIG-UHFFFAOYSA-N 3-[[2-[[3-(1-phenylethylcarbamoylamino)benzoyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CC=CC=1C(C)NC(=O)NC(C=1)=CC=CC=1C(=O)NCC(=O)NC(CC(O)=O)C1=CC=CN=C1 LZPNSKVTBKQVIG-UHFFFAOYSA-N 0.000 claims 1
- AQBDADLMLLCKCT-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-3-(3-methylthiophen-2-yl)propanoic acid Chemical compound C1=CSC(C(CC(O)=O)NC(=O)CNC(=O)C=2C=C(NC=NN)C=CC=2)=C1C AQBDADLMLLCKCT-UHFFFAOYSA-N 0.000 claims 1
- UEMWYLFRZDPSGH-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-3-pyrimidin-5-ylpropanoic acid Chemical compound NN=CNC=1C=C(C=CC=1)C(=O)NCC(=O)NC(CC(=O)O)C=1C=NC=NC=1 UEMWYLFRZDPSGH-UHFFFAOYSA-N 0.000 claims 1
- GDNLHEKXAKGXRP-UHFFFAOYSA-N 3-[[2-[[3-(hydrazinylmethylideneamino)benzoyl]amino]acetyl]amino]-4-[(4-methylphenyl)sulfonylamino]butanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCC(CC(O)=O)NC(=O)CNC(=O)C1=CC=CC(N=CNN)=C1 GDNLHEKXAKGXRP-UHFFFAOYSA-N 0.000 claims 1
- YTYVFKGMTBHACX-UHFFFAOYSA-N 3-[[2-[[3-(naphthalen-1-ylmethylcarbamoylamino)benzoyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CC(NC(=O)NCC=2C3=CC=CC=C3C=CC=2)=CC=1C(=O)NCC(=O)NC(CC(=O)O)C1=CC=CN=C1 YTYVFKGMTBHACX-UHFFFAOYSA-N 0.000 claims 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/28—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to cyano groups, e.g. cyanoguanidines, dicyandiamides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/48—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C317/50—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
- C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- Neurology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US327795P | 1995-08-30 | 1995-08-30 | |
PCT/US1996/013500 WO1997008145A1 (en) | 1995-08-30 | 1996-08-27 | Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists |
Publications (3)
Publication Number | Publication Date |
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NO980817D0 NO980817D0 (no) | 1998-02-26 |
NO980817L NO980817L (no) | 1998-04-24 |
NO311671B1 true NO311671B1 (no) | 2002-01-02 |
Family
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Family Applications (1)
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NO19980817A NO311671B1 (no) | 1995-08-30 | 1998-02-26 | Meta-guanidin-, urea-, tiourea- eller azacykliske aminobenzosyrederivater som integrin-antagonister samt preparaterinneholdende forbindelsene |
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US (2) | US6028223A (ru) |
EP (1) | EP0850221B1 (ru) |
JP (1) | JPH11510814A (ru) |
KR (1) | KR100481285B1 (ru) |
CN (1) | CN1085980C (ru) |
AT (1) | ATE203234T1 (ru) |
AU (1) | AU702487B2 (ru) |
BR (1) | BR9610422A (ru) |
CA (1) | CA2230209A1 (ru) |
CZ (1) | CZ293323B6 (ru) |
DE (1) | DE69613985T2 (ru) |
DK (1) | DK0850221T3 (ru) |
ES (1) | ES2161373T3 (ru) |
GR (1) | GR3036751T3 (ru) |
IL (1) | IL123164A (ru) |
MX (1) | MX9801716A (ru) |
NO (1) | NO311671B1 (ru) |
NZ (1) | NZ318926A (ru) |
PL (1) | PL186370B1 (ru) |
PT (1) | PT850221E (ru) |
RO (2) | RO118289B1 (ru) |
RU (1) | RU2196769C2 (ru) |
WO (1) | WO1997008145A1 (ru) |
ZA (1) | ZA967379B (ru) |
Families Citing this family (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5952306A (en) * | 1996-01-16 | 1999-09-14 | Merck & Co., Inc. | Integrin receptor antagonists |
GB9723789D0 (en) * | 1997-11-12 | 1998-01-07 | Zeneca Ltd | Chemical compounds |
US6066740A (en) * | 1997-11-25 | 2000-05-23 | The Procter & Gamble Company | Process for making 2-amino-2-imidazoline, guanidine and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives |
IL136584A (en) * | 1997-12-23 | 2005-03-20 | Aventis Pharma Ltd | SUBSTITUTED beta-ALANINES, PHARMACEUTICAL COMPOSITIONS COMPRISING THEM AND USES THEREOF |
US6001855A (en) * | 1998-01-02 | 1999-12-14 | Hoffman-La Roche Inc. | Thiazole derivatives |
US6197794B1 (en) | 1998-01-08 | 2001-03-06 | Celltech Therapeutics Limited | Phenylalanine derivatives |
US6329372B1 (en) | 1998-01-27 | 2001-12-11 | Celltech Therapeutics Limited | Phenylalanine derivatives |
ZA991105B (en) | 1998-03-04 | 2000-02-11 | Searle & Co | Synthesis of chiral beta-amino acids. |
US6172256B1 (en) | 1998-03-04 | 2001-01-09 | G.D. Searle & Co. | Chiral-β-amino acid compounds and derivatives thereof |
US6372719B1 (en) | 1998-03-04 | 2002-04-16 | Jay Cunningham | ανβ3 integrin antagonists in combination with chemotherapeutic agents |
ZA994406B (en) * | 1998-03-04 | 2000-02-11 | Searle & Co | Meta-azacyclic amino benzoic acid and derivatives thereof. |
US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
US6524553B2 (en) | 1998-03-31 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
IL138093A0 (en) | 1998-03-31 | 2001-10-31 | Du Pont Pharm Co | Pharmaceuticals for the imaging of angiogenic disorders |
US6548663B1 (en) | 1998-03-31 | 2003-04-15 | Bristol-Myers Squibb Pharma Company | Benzodiazepine vitronectin receptor antagonist pharmaceuticals |
US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
US6420558B1 (en) | 1998-04-09 | 2002-07-16 | Meiji Seika Kaisha, Ltd. | Aminopiperidine derivates as integrin αvβ3 antagonists |
CN1304406A (zh) * | 1998-04-10 | 2001-07-18 | G·D·瑟尔公司 | 作为玻连蛋白拮抗剂的杂环甘氨酰β-丙氨酸衍生物 |
US6689754B1 (en) | 1998-04-10 | 2004-02-10 | G. D. Searle & Co. | Heterocyclic glycyl β-alanine derivatives |
WO1999052879A1 (en) * | 1998-04-14 | 1999-10-21 | American Home Products Corporation | Acylresorcinol derivatives as selective vitronectin receptor inhibitors |
GB9811159D0 (en) | 1998-05-22 | 1998-07-22 | Celltech Therapeutics Ltd | Chemical compounds |
GB9811969D0 (en) | 1998-06-03 | 1998-07-29 | Celltech Therapeutics Ltd | Chemical compounds |
GB9814414D0 (en) | 1998-07-03 | 1998-09-02 | Celltech Therapeutics Ltd | Chemical compounds |
GB9916374D0 (en) * | 1998-07-23 | 1999-09-15 | Zeneca Ltd | Chemical compounds |
WO2000005223A2 (en) * | 1998-07-23 | 2000-02-03 | Astrazeneca Ab | Heterocyclic derivatives and their use as integrin inhibitors |
GB9821061D0 (en) | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
GB9821222D0 (en) | 1998-09-30 | 1998-11-25 | Celltech Therapeutics Ltd | Chemical compounds |
GB9825652D0 (en) | 1998-11-23 | 1999-01-13 | Celltech Therapeutics Ltd | Chemical compounds |
GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
DE69936148T2 (de) * | 1998-12-18 | 2008-01-24 | Bristol-Myers Squibb Pharma Co. | Vitronektinrezeptorantagonist-arzneimittel |
US6511649B1 (en) | 1998-12-18 | 2003-01-28 | Thomas D. Harris | Vitronectin receptor antagonist pharmaceuticals |
US6794518B1 (en) | 1998-12-18 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
US6569402B1 (en) | 1998-12-18 | 2003-05-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
EP1140864A2 (en) | 1998-12-18 | 2001-10-10 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
CA2727746A1 (en) | 1998-12-18 | 2000-06-22 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
JP2002533416A (ja) | 1998-12-23 | 2002-10-08 | ジー.ディー.サール & カンパニー | 新形成の治療における組み合わせ治療としてのシクロオキシゲナーゼ−2インヒビターおよび一つまたはそれ以上の抗腫瘍薬の使用方法 |
US6291503B1 (en) | 1999-01-15 | 2001-09-18 | Bayer Aktiengesellschaft | β-phenylalanine derivatives as integrin antagonists |
GB9908355D0 (en) * | 1999-04-12 | 1999-06-09 | Rhone Poulenc Rorer Ltd | Chemical compounds |
HUP0200803A3 (en) * | 1999-04-12 | 2002-12-28 | Aventis Pharma Ltd West Mallin | Substituted bicyclic heteroaryl compounds as integrin antagonists, pharmaceutical compositions containing them and the intermediates |
US6586187B1 (en) | 1999-04-14 | 2003-07-01 | Wyeth | Methods for solid phase combinatorial synthesis of integrin inhibitors |
AR023480A1 (es) * | 1999-04-14 | 2002-09-04 | American Home Prod | Metodos para la sintesis combinatoria en fase solida de inhibidores de integrina |
MXPA01010834A (es) * | 1999-04-28 | 2002-04-24 | Basf Ag | Antagonistas de los receptores para integrina. |
WO2000068213A1 (en) * | 1999-05-05 | 2000-11-16 | Aventis Pharma Limited | Substituted bicyclic compounds |
US6518283B1 (en) | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
BR0012683A (pt) | 1999-07-21 | 2002-04-16 | American Home Prod | Antagonistas bicìclicos seletivos para a integrina alfavbeta3 |
EP1209152A4 (en) | 1999-08-05 | 2003-03-12 | Meiji Seika Kaisha | OMEGA-AMINO-ALPHA-HYDROXY-CARBONIC ACID DERIVATIVES WITH AN INTEGRIN ALPHA V BETA ANTAGONISM |
CA2383086A1 (en) * | 1999-09-08 | 2001-03-15 | Joseph P. Steiner | Non-peptidic cyclophilin binding compounds and their use |
US6534513B1 (en) | 1999-09-29 | 2003-03-18 | Celltech R&D Limited | Phenylalkanoic acid derivatives |
CZ20011872A3 (cs) | 1999-09-29 | 2002-03-13 | Ortho-Mcneil Pharmaceutical, Inc. | Isonipekotamidy pro léčbu onemocnění zprostředkovaných integriny |
AU781747B2 (en) * | 1999-10-08 | 2005-06-09 | Meiji Seika Kaisha Ltd. | 3-aminopiperidine derivatives as integrin alphavbeta3 antagonists |
US6849639B2 (en) * | 1999-12-14 | 2005-02-01 | Amgen Inc. | Integrin inhibitors and their methods of use |
US6455539B2 (en) | 1999-12-23 | 2002-09-24 | Celltech R&D Limited | Squaric acid derivates |
AU2001248553A1 (en) | 2000-04-17 | 2001-10-30 | Celltech R And D Limited | Enamine derivatives as cell adhesion molecules |
US6545013B2 (en) | 2000-05-30 | 2003-04-08 | Celltech R&D Limited | 2,7-naphthyridine derivatives |
US6403608B1 (en) | 2000-05-30 | 2002-06-11 | Celltech R&D, Ltd. | 3-Substituted isoquinolin-1-yl derivatives |
AU2001267753A1 (en) | 2000-07-07 | 2002-01-21 | Celltech R And D Limited | Squaric acid derivatives containing a bicyclic heteroaromatic ring as integrin antagonists |
WO2002010136A1 (en) | 2000-08-02 | 2002-02-07 | Celltech R & D Limited | 3-substituted isoquinolin-1-yl derivatives |
US6720327B2 (en) * | 2000-09-27 | 2004-04-13 | Pharmacia Corporation | Lactone integrin antagonists |
US20020072500A1 (en) * | 2000-09-27 | 2002-06-13 | Thomas Rogers | Hydroxy acid integrin antagonists |
CA2432908A1 (en) | 2000-12-20 | 2002-06-27 | Bristol-Myers Squibb Pharma Company | Diamines as modulators of chemokine receptor activity |
EP1360173A2 (en) | 2001-01-25 | 2003-11-12 | Guilford Pharmaceuticals Inc. | Trisubstituted carbocyclic cyclophilin binding compounds and their use |
ITTO20010110A1 (it) | 2001-02-08 | 2002-08-08 | Rotta Research Lab | Nuovi derivati benzamidinici dotati di attivita' anti-infiammatoria ed immunosoppressiva. |
HU229431B1 (en) | 2001-02-20 | 2013-12-30 | Chugai Pharmaceutical Co Ltd | Azoles as malonyl-coa decarboxylase inhibitors useful as metabolic modulators |
US7709510B2 (en) | 2001-02-20 | 2010-05-04 | Chugai Seiyaku Kabushiki Kaisha | Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators |
DE60208186T2 (de) | 2001-04-09 | 2006-08-24 | Ortho-Mcneil Pharmaceutical Research Inc. | Chinazolin- und chinazolinähnliche verbindungen zur behandlung von integrin-vermittelten erkrankungen |
US20040019206A1 (en) * | 2001-09-27 | 2004-01-29 | Peter Ruminiski | Lactone integrin antagonists |
WO2003059251A2 (en) | 2001-10-22 | 2003-07-24 | The Scripps Research Institute | Antibody targeting compounds |
TW200307671A (en) * | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
TWI281470B (en) * | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
AU2003299600A1 (en) * | 2002-12-20 | 2004-07-29 | Pharmacia Corpration | The r-isomer of beta amino acid compounds as integrin receptor antagonists derivatives |
JP4648317B2 (ja) | 2003-08-01 | 2011-03-09 | 中外製薬株式会社 | マロニル−CoAデカルボキシラーゼ阻害剤として有用なピペリジン化合物 |
WO2005037258A2 (en) | 2003-08-01 | 2005-04-28 | Chugai Seiyaku Kabushiki Kaisha | Cyanoguanidine-based azole compounds useful as malonyl-coa decarboxylase inhibitors |
US7696365B2 (en) | 2003-08-01 | 2010-04-13 | Chugai Seiyaku Kabushiki Kaisha | Heterocyclic compounds useful as malonyl-CoA decarboxylase inhibitors |
UA87854C2 (en) | 2004-06-07 | 2009-08-25 | Мерк Энд Ко., Инк. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
CA2630415A1 (en) * | 2005-10-20 | 2007-04-26 | The Scripps Research Institute | Fc labeling for immunostaining and immunotargeting |
CA2721135A1 (en) | 2007-06-13 | 2008-12-24 | Wayne State University Board Of Governors | A zwitterion solution for low-volume therapeutic delivery |
WO2008157288A2 (en) | 2007-06-13 | 2008-12-24 | Wayne State University Board Of Governors | A baclofen solution for low-volume therapeutic delivery |
EP2217238B1 (en) | 2007-11-08 | 2014-03-12 | The General Hospital Corporation | Methods and compositions for the treatment of proteinuric diseases |
EP2222636B1 (en) | 2007-12-21 | 2013-04-10 | Ligand Pharmaceuticals Inc. | Selective androgen receptor modulators (sarms) and uses thereof |
JP5315710B2 (ja) * | 2008-02-07 | 2013-10-16 | セントラル硝子株式会社 | 1−ブロモ−3−フルオロ−5−ジフルオロメチルベンゼンの製造方法 |
JP5762971B2 (ja) | 2008-12-03 | 2015-08-12 | プレシディオ ファーマシューティカルズ インコーポレイテッド | Hcvns5aの阻害剤 |
JP2012517447A (ja) | 2009-02-10 | 2012-08-02 | ザ スクリプス リサーチ インスティチュート | 化学的にプログラムされたワクチン接種法 |
US8633322B2 (en) | 2009-10-29 | 2014-01-21 | Janssen Pharmaceutica Nv | Alkynyl derivatives useful as DPP-1 inhibitors |
CN102211994B (zh) * | 2010-04-06 | 2014-09-17 | 上海药明康德新药开发有限公司 | 3-(2-溴苯基)丙酸的工业化合成方法 |
US8716226B2 (en) | 2012-07-18 | 2014-05-06 | Saint Louis University | 3,5 phenyl-substituted beta amino acid derivatives as integrin antagonists |
WO2014015054A1 (en) * | 2012-07-18 | 2014-01-23 | Saint Louis University | Beta amino acid derivatives as integrin antagonists |
CN104602690A (zh) * | 2012-08-29 | 2015-05-06 | 默克专利股份有限公司 | 用于治疗骨关节炎的ddr2抑制剂 |
WO2015021092A1 (en) * | 2013-08-07 | 2015-02-12 | Arrowhead Research Corporation | Polyconjugates for delivery of rnai triggers to tumor cells in vivo |
CA2920220A1 (en) * | 2013-09-06 | 2015-03-12 | Sandoz Ag | Synthesis of peptide epoxy ketones |
SG11201609050UA (en) | 2014-05-30 | 2016-12-29 | Pfizer | Carbonitrile derivatives as selective androgen receptor modulators |
CN104326937B (zh) * | 2014-09-03 | 2016-08-24 | 天津市肿瘤研究所 | 抗肿瘤化合物及其医药用途 |
CN105820093A (zh) * | 2015-01-05 | 2016-08-03 | 齐鲁工业大学 | 一种n-苄基-5-[3-(2,5-二乙氧基-4-甲磺酰基-苄基)-脲基]-2-乙氧基苯甲酰胺新化合物、制备方法及用途 |
ES2806276T3 (es) * | 2015-12-30 | 2021-02-17 | Univ Saint Louis | Derivados de ácido aminobenzoico meta-azaciclicos como antagonistas pan-integrina |
WO2021044413A1 (en) * | 2019-09-03 | 2021-03-11 | Salzman Group Ltd. | Atp-regulated potassium channel openers comprising guanidine and uses thereof |
KR102334997B1 (ko) * | 2019-11-27 | 2021-12-03 | 한국화학연구원 | 보풀 속 식물 추출물을 유효성분으로 포함하는 구강질환 또는 골질환의 예방 또는 치료용 조성물 |
CN115551846B (zh) | 2020-05-14 | 2024-03-08 | Ube株式会社 | 1,4,5,6-四氢嘧啶-2-胺衍生物 |
CN116744912A (zh) * | 2021-01-11 | 2023-09-12 | 苏州华明道康生物医药有限公司 | 取代的水杨酰胺化合物及其用途 |
WO2023275715A1 (en) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Metabolites of selective androgen receptor modulators |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US445796A (en) * | 1891-02-03 | Half to moses g | ||
JPS6193163A (ja) * | 1984-10-12 | 1986-05-12 | Ishihara Sangyo Kaisha Ltd | N−ベンゾイル−n′−フエニルウレア系化合物、それらの製造方法並びにそれらを含有する抗癌剤 |
IL90337A0 (en) * | 1988-05-24 | 1989-12-15 | Pfizer | Aromatic and heterocyclic carboxamide derivatives as antineoplastic agents |
US4874864A (en) * | 1988-05-24 | 1989-10-17 | Pfizer Inc. | Benzamide protease inhibitors |
US5256812A (en) * | 1989-01-31 | 1993-10-26 | Hoffmann-La Roche Inc. | Carboxamides and sulfonamides |
DE4007611C1 (ru) * | 1990-03-09 | 1991-05-16 | Deutsche Forschungsanstalt Fuer Luft- Und Raumfahrt Ev, 5300 Bonn, De | |
CA2037153A1 (en) * | 1990-03-09 | 1991-09-10 | Leo Alig | Acetic acid derivatives |
US5273982A (en) | 1990-03-09 | 1993-12-28 | Hoffmann-La Roche Inc. | Acetic acid derivatives |
NZ239846A (en) * | 1990-09-27 | 1994-11-25 | Merck & Co Inc | Sulphonamide derivatives and pharmaceutical compositions thereof |
IL99537A (en) * | 1990-09-27 | 1995-11-27 | Merck & Co Inc | Fibrinogen receptor antagonists and pharmaceutical preparations containing them |
AU8868991A (en) * | 1990-11-15 | 1992-06-11 | Pentapharm Ag | Meta-substituted phenyl alanine derivatives |
DE4102024A1 (de) * | 1991-01-24 | 1992-07-30 | Thomae Gmbh Dr K | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
GB9105771D0 (en) * | 1991-03-19 | 1991-05-01 | Cancer Res Inst Royal | Anti-cancer compounds |
WO1993008823A1 (en) * | 1991-11-06 | 1993-05-13 | Tanabe Seiyaku Co., Ltd. | Guanidinyl and related cell adhesion modulation compounds |
GB9205907D0 (en) * | 1992-03-18 | 1992-04-29 | Cancer Res Inst Royal | Anti-cancer compounds |
DE4301747A1 (de) | 1993-01-23 | 1994-07-28 | Cassella Ag | Substituierte Aminoverbindungen, ihre Herstellung und ihre Verwendung |
CN1118139A (zh) * | 1993-02-22 | 1996-03-06 | 麦克公司 | 纤维蛋白原受体拮抗剂 |
DE4309867A1 (de) | 1993-03-26 | 1994-09-29 | Cassella Ag | Neue Harnstoffderivate, ihre Herstellung und Verwendung |
DE4310632A1 (de) * | 1993-04-01 | 1994-10-06 | Merck Patent Gmbh | Lineare Adhäsionsinhibitoren |
HUT70045A (en) * | 1993-06-17 | 1995-09-28 | Takeda Chemical Industries Ltd | 2-piperazinone derivatives parmaceutical compositions containing them and process for producing them |
KR100308839B1 (ko) * | 1993-09-09 | 2002-10-04 | 메렐 파마슈티칼스 인크. | 디플루오로 스타톤 항바이러스성 유사체 |
DE4336758A1 (de) * | 1993-10-28 | 1995-05-04 | Merck Patent Gmbh | Lineare Adhäsionsinhibitoren |
DE4338944A1 (de) | 1993-11-15 | 1995-05-18 | Cassella Ag | Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung |
US5981478A (en) * | 1993-11-24 | 1999-11-09 | La Jolla Cancer Research Foundation | Integrin-binding peptides |
EP0656348B1 (de) * | 1993-12-03 | 2000-05-03 | F. Hoffmann-La Roche Ag | Essigsäurederivate als Arzneimittel |
US5753230A (en) | 1994-03-18 | 1998-05-19 | The Scripps Research Institute | Methods and compositions useful for inhibition of angiogenesis |
US5770565A (en) * | 1994-04-13 | 1998-06-23 | La Jolla Cancer Research Center | Peptides for reducing or inhibiting bone resorption |
AU701776B2 (en) * | 1994-05-27 | 1999-02-04 | Merck & Co., Inc. | Compounds for inhibiting osteoclast-mediated bone resorption |
JPH10504807A (ja) * | 1994-06-29 | 1998-05-12 | スミスクライン・ビーチャム・コーポレイション | ビトロネクチン受容体拮抗剤 |
MX9700041A (es) * | 1994-06-29 | 1997-04-30 | Smithkline Beecham Corp | Antagonistas de receptor de vitronectina. |
WO1996026190A1 (en) * | 1995-02-22 | 1996-08-29 | Smithkline Beecham Corporation | Integrin receptor antagonists |
US5681820A (en) * | 1995-05-16 | 1997-10-28 | G. D. Searle & Co. | Guanidinoalkyl glycine β-amino acids useful for inhibiting tumor metastasis |
US6100423A (en) * | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
US6013651A (en) * | 1995-08-30 | 2000-01-11 | G. D. Searle & Co. | Meta-azacyclic amino benzoic acid compounds and derivatives thereof |
CA2250464A1 (en) * | 1996-03-29 | 1997-10-09 | G.D. Searle & Co. | Meta-substituted phenylene derivatives and their use as alphavbeta3 integrin antagonists or inhibitors |
ATE212978T1 (de) * | 1996-03-29 | 2002-02-15 | Searle & Co | Para-substituierte phenylpropansäure derivate als integrin-antagonisten |
US6372719B1 (en) * | 1998-03-04 | 2002-04-16 | Jay Cunningham | ανβ3 integrin antagonists in combination with chemotherapeutic agents |
-
1996
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- 1996-08-27 DK DK96932142T patent/DK0850221T3/da active
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- 1996-08-27 AU AU71039/96A patent/AU702487B2/en not_active Ceased
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- 1996-08-27 CZ CZ1998341A patent/CZ293323B6/cs not_active IP Right Cessation
- 1996-08-27 WO PCT/US1996/013500 patent/WO1997008145A1/en active IP Right Grant
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- 1996-08-27 AT AT96932142T patent/ATE203234T1/de not_active IP Right Cessation
- 1996-08-27 RO ROA200101069A patent/RO118290B1/ro unknown
- 1996-08-30 ZA ZA9607379A patent/ZA967379B/xx unknown
-
1998
- 1998-02-26 NO NO19980817A patent/NO311671B1/no unknown
- 1998-12-18 US US09/215,229 patent/US6831199B1/en not_active Expired - Fee Related
-
2001
- 2001-09-28 GR GR20010401608T patent/GR3036751T3/el not_active IP Right Cessation
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