CA2446282A1 - 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives - Google Patents
2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives Download PDFInfo
- Publication number
- CA2446282A1 CA2446282A1 CA002446282A CA2446282A CA2446282A1 CA 2446282 A1 CA2446282 A1 CA 2446282A1 CA 002446282 A CA002446282 A CA 002446282A CA 2446282 A CA2446282 A CA 2446282A CA 2446282 A1 CA2446282 A1 CA 2446282A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- methyl
- propionylamino
- formula
- compound
- 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
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- 125000003118 aryl group Chemical group 0.000 title claims description 18
- 239000002253 acid Substances 0.000 title description 15
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 277
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 241001465754 Metazoa Species 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 230000002062 proliferating effect Effects 0.000 claims abstract description 13
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- -1 mercapto, sulfo Chemical group 0.000 claims description 81
- 150000003839 salts Chemical class 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 206010028980 Neoplasm Diseases 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 33
- 125000003107 substituted aryl group Chemical group 0.000 claims description 31
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 10
- 229910052796 boron Inorganic materials 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 241000282412 Homo Species 0.000 claims description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000006383 alkylpyridyl group Chemical group 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 108010016626 Dipeptides Proteins 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000005717 substituted cycloalkylene group Chemical group 0.000 claims description 3
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- YYXCDWMJTBCHJW-AIUMHDJVSA-N pubchem11583 Chemical compound C1[C@@]2([H])C(C)(C)[C@]1([H])C[C@H]1OB([C@@H](N)CC(C)C)O[C@]12C YYXCDWMJTBCHJW-AIUMHDJVSA-N 0.000 claims 3
- BIGIFWJGBNONPK-APGVRMINSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(3,4-dimethoxyphenyl)-2-[[2-(3-phenoxyphenyl)acetyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)CC1=CC=CC(OC=2C=CC=CC=2)=C1 BIGIFWJGBNONPK-APGVRMINSA-N 0.000 claims 2
- NOCYZLFJDNEMRY-DTXPUJKBSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(4-methoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 NOCYZLFJDNEMRY-DTXPUJKBSA-N 0.000 claims 2
- MIFUSOBKODRKPC-OLWNVYNHSA-N [(1r)-3-methyl-1-[[(2s)-4-methyl-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]pentanoyl]amino]butyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)=C1 MIFUSOBKODRKPC-OLWNVYNHSA-N 0.000 claims 2
- SQXZJGZFOCSKHG-VXBWKZIMSA-N (2S)-N-[(2S)-1-[[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]amino]-1-oxopropan-2-yl]-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC=1C=C(C=CC=1)C=1C=CC=CC=1)C1=CC(OC)=C(OC)C(OC)=C1 SQXZJGZFOCSKHG-VXBWKZIMSA-N 0.000 claims 1
- RVMYSKJBWGAPPQ-DQEYMECFSA-N (2s)-2-[[(2s)-3-(3,4-dimethoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-4-methylpentanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC1=CC=CC(C=2C=CC=CC=2)=C1 RVMYSKJBWGAPPQ-DQEYMECFSA-N 0.000 claims 1
- VOLLGGPORYHKST-UIOOFZCWSA-N (2s)-2-[[(2s)-3-(4-methoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-4-methylpentanoic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC1=CC=CC(C=2C=CC=CC=2)=C1 VOLLGGPORYHKST-UIOOFZCWSA-N 0.000 claims 1
- MQTFRDWVOXMYPD-NQAOIOOJSA-N (2s)-3-methyl-n-[3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl]-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]butanamide Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@@H](C(C)C)C(=O)NC(CC(C)C)B2OC(C)(C)C(C)(C)O2)=C1 MQTFRDWVOXMYPD-NQAOIOOJSA-N 0.000 claims 1
- QWWDLTHXPFKTAS-DQEYMECFSA-N (2s)-4-methyl-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]pentanoic acid Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@@H](CC(C)C)C(O)=O)=C1 QWWDLTHXPFKTAS-DQEYMECFSA-N 0.000 claims 1
- LZQSSVFYDZMBSS-RKJZVWEHSA-N (s)-2-(3-isopropyl-phenylamino)-n-{(s)-1-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-ethyl}-3-(3,4,5-trimethoxy-phenyl)-propionamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC=1C=C(C=CC=1)C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 LZQSSVFYDZMBSS-RKJZVWEHSA-N 0.000 claims 1
- WTYBZMWTNRGGBL-CQKAUHNLSA-N (s)-2-(biphenyl-3-ylamino)-3-(3,4-dimethoxy-phenyl)-n-{(s)-1-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec -4-yl)-butylcarbamoyl]-ethyl}-propionamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC=1C=C(C=CC=1)C=1C=CC=CC=1)C1=CC=C(OC)C(OC)=C1 WTYBZMWTNRGGBL-CQKAUHNLSA-N 0.000 claims 1
- YVCJUCBEQOIXCO-HEXCTAKASA-N (s)-2-(biphenyl-3-ylamino)-3-(4-methoxy-phenyl)-n-{(s)-1-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-ethyl}-propionamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC=1C=C(C=CC=1)C=1C=CC=CC=1)C1=CC=C(OC)C=C1 YVCJUCBEQOIXCO-HEXCTAKASA-N 0.000 claims 1
- GHDYDVSRZOPPCS-NJEUOHNNSA-N (s)-2-(biphenyl-3-ylamino)-n-{(s)-1-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-ethyl}-3-(2,3,4-trimethoxy-phenyl)-propionamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC=1C=C(C=CC=1)C=1C=CC=CC=1)C1=CC=C(OC)C(OC)=C1OC GHDYDVSRZOPPCS-NJEUOHNNSA-N 0.000 claims 1
- GNNZQYZRVDKZDM-OQGSPSPTSA-N (s)-2-[(s)-2-(biphenyl-3-ylamino)-3-(3,4-dimethoxy-phenyl)-propionylamino]-3 methyl-n-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butyl]-butyramide Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])C(C)C)NC=1C=C(C=CC=1)C=1C=CC=CC=1)C1=CC=C(OC)C(OC)=C1 GNNZQYZRVDKZDM-OQGSPSPTSA-N 0.000 claims 1
- PVSZHCDJYVWTSI-LSVRKRGFSA-N (s)-2-[(s)-2-(biphenyl-3-ylamino)-3-(4-methoxy-phenyl)-propionylamino]-3-methyl-n-[(r)-2-phenyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-ethyl]-butyramide Chemical compound C([C@@H](B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(OC)=CC=1)NC=1C=C(C=CC=1)C=1C=CC=CC=1)C(C)C)C1=CC=CC=C1 PVSZHCDJYVWTSI-LSVRKRGFSA-N 0.000 claims 1
- ONYUIBVIRUYLEH-ISTAWWLZSA-N (s)-n-{(s)-1-[(r)-3-methyl-1-((1s,2s,6r,8s)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-butylcarbamoyl]-ethyl}-2-(3-phenyl-propionylamino)-3-(2,3,4-trimethoxy-phenyl)-propionamide Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])NC(=O)CCC=1C=CC=CC=1)C1=CC=C(OC)C(OC)=C1OC ONYUIBVIRUYLEH-ISTAWWLZSA-N 0.000 claims 1
- STFNYYMZCIIMGS-UWILOXQKSA-N C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])C(C)C)NC=1C=C(C=CC=1)C=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)B1O[C@@]2(C)[C@@]3([H])C[C@](C3(C)C)(C[C@H]2O1)[H])C(C)C)NC=1C=C(C=CC=1)C=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 STFNYYMZCIIMGS-UWILOXQKSA-N 0.000 claims 1
- CCMMLNAYXJIYSX-NAYUSWPISA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(3,4-dimethoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 CCMMLNAYXJIYSX-NAYUSWPISA-N 0.000 claims 1
- SIVDXIDADYCFIS-VFXRXZKFSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(3,4-dimethoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]propanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 SIVDXIDADYCFIS-VFXRXZKFSA-N 0.000 claims 1
- FFYWDLQQTKZDLV-ZDCRTTOTSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(4-methoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-3-methylbutanoyl]amino]-2-phenylethyl]boronic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 FFYWDLQQTKZDLV-ZDCRTTOTSA-N 0.000 claims 1
- BCRCUSHGQVRUGQ-CHQNGUEUSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(4-methoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 BCRCUSHGQVRUGQ-CHQNGUEUSA-N 0.000 claims 1
- JPHIPLCHJZGVRY-NUKCWJJBSA-N [(1r)-1-[[(2s)-2-[[(2s)-3-(4-methoxyphenyl)-2-(3-phenylanilino)propanoyl]amino]propanoyl]amino]-3-methylbutyl]boronic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 JPHIPLCHJZGVRY-NUKCWJJBSA-N 0.000 claims 1
- CFKMEDWCTRYERJ-SKTSAMEXSA-N [(1r)-1-[[(2s)-3-methyl-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]butanoyl]amino]-2-phenylethyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=2C=CC=CC=2)B(O)O)=C1 CFKMEDWCTRYERJ-SKTSAMEXSA-N 0.000 claims 1
- XZXKVJSYPUKVEO-FKCXQASGSA-N [(1r)-3-methyl-1-[[(2r)-3-methyl-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]butanoyl]amino]butyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC(C)C)B(O)O)=C1 XZXKVJSYPUKVEO-FKCXQASGSA-N 0.000 claims 1
- LCDJPEAMOSFROR-PTJQVGQKSA-N [(1r)-3-methyl-1-[[(2s)-2-[[(2s)-2-(3-phenylanilino)-3-(2,3,4-trimethoxyphenyl)propanoyl]amino]propanoyl]amino]butyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B(O)O)NC1=CC=CC(C=2C=CC=CC=2)=C1 LCDJPEAMOSFROR-PTJQVGQKSA-N 0.000 claims 1
- PZFHDQKICAUUFL-VFXRXZKFSA-N [(1r)-3-methyl-1-[[(2s)-2-[[(2s)-2-(3-phenylanilino)-3-(3,4,5-trimethoxyphenyl)propanoyl]amino]propanoyl]amino]butyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC(C[C@H](NC=2C=C(C=CC=2)C=2C=CC=CC=2)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B(O)O)=C1 PZFHDQKICAUUFL-VFXRXZKFSA-N 0.000 claims 1
- URJILNGJEMDJRO-APTRMMRNSA-N [(1r)-3-methyl-1-[[(2s)-2-[[(2s)-2-(3-phenylpropanoylamino)-3-(2,3,4-trimethoxyphenyl)propanoyl]amino]propanoyl]amino]butyl]boronic acid Chemical compound COC1=C(OC)C(OC)=CC=C1C[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)CCC1=CC=CC=C1 URJILNGJEMDJRO-APTRMMRNSA-N 0.000 claims 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0113096.2 | 2001-05-30 | ||
| GB0113096A GB0113096D0 (en) | 2001-05-30 | 2001-05-30 | Organic compounds |
| GB0129394A GB0129394D0 (en) | 2001-12-07 | 2001-12-07 | Organic compounds |
| GB0129394.3 | 2001-12-07 | ||
| PCT/EP2002/005937 WO2002096933A1 (en) | 2001-05-30 | 2002-05-29 | 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2446282A1 true CA2446282A1 (en) | 2002-12-05 |
Family
ID=26246132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002446282A Abandoned CA2446282A1 (en) | 2001-05-30 | 2002-05-29 | 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US6933290B2 (https=) |
| EP (1) | EP1399468B1 (https=) |
| JP (1) | JP4416501B2 (https=) |
| CN (1) | CN100415770C (https=) |
| AT (1) | ATE317850T1 (https=) |
| BR (1) | BR0210112A (https=) |
| CA (1) | CA2446282A1 (https=) |
| DE (1) | DE60209227T2 (https=) |
| ES (1) | ES2258149T3 (https=) |
| PT (1) | PT1399468E (https=) |
| WO (1) | WO2002096933A1 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002096933A1 (en) * | 2001-05-30 | 2002-12-05 | Novartis Ag | 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives |
| AU2003219652A1 (en) * | 2002-01-08 | 2003-07-30 | Eisai Co. Ltd. | Eponemycin and epoxomicin analogs and uses thereof |
| WO2004043926A1 (en) * | 2002-11-11 | 2004-05-27 | Bayer Healthcare Ag | Phenyl or heteroaryl amino alkane derivatives as ip receptor antagonist |
| US7576206B2 (en) | 2003-08-14 | 2009-08-18 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| US7223745B2 (en) | 2003-08-14 | 2007-05-29 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| US7468383B2 (en) | 2005-02-11 | 2008-12-23 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| JP5321061B2 (ja) | 2005-08-11 | 2013-10-23 | アリアド・ファーマシューティカルズ・インコーポレイテッド | 不飽和複素環誘導体 |
| WO2007059106A2 (en) | 2005-11-14 | 2007-05-24 | Ariad Gene Therapeutics, Inc. | Administration of mntor inhibitor to treat patients with cancer |
| EA034598B1 (ru) | 2005-12-23 | 2020-02-25 | Ариад Фармасьютикалз, Инк. | Применение бициклических гетероарильных соединений для лечения рака |
| PL2178888T3 (pl) | 2007-08-06 | 2012-11-30 | Millennium Pharm Inc | Inhibitory proteasomów |
| MX353308B (es) | 2008-05-21 | 2018-01-08 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| EP2730579A1 (en) | 2008-06-17 | 2014-05-14 | Millennium Pharmaceuticals, Inc. | Boronate ester compounds and pharmaceutical compositions thereof |
| AR075090A1 (es) | 2008-09-29 | 2011-03-09 | Millennium Pharm Inc | Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden. |
| CA2743449C (en) | 2008-11-12 | 2016-10-18 | Ariad Pharmaceuticals, Inc. | Pyrazinopyrazines and derivatives as kinase inhibitors |
| WO2010096574A1 (en) | 2009-02-20 | 2010-08-26 | Lisanti Michael P | A method of diagnosis or prognosis of a neoplasm comprising determining the level of expression of a protein in stromal cells adjacent to the neoplasm |
| AU2010341530B2 (en) | 2009-12-22 | 2016-03-10 | Cephalon, Inc. | Proteasome inhibitors and processes for their preparation, purification and use |
| EP2542238B1 (en) * | 2010-03-01 | 2015-08-12 | Onyx Therapeutics, Inc. | Compounds for immunoproteasome inhibition |
| CN102946879B (zh) | 2010-04-19 | 2015-04-22 | 尼基制药公司 | 一种蛋白酶体抑制剂和镓络合物在制备治疗增殖性疾病的药物中的应用 |
| WO2013112881A1 (en) | 2012-01-27 | 2013-08-01 | Thomas Jefferson University | Mct protein inhibitor-related prognostic and therapeutic methods |
| CN103421032B (zh) * | 2012-05-17 | 2016-01-20 | 上海创诺制药有限公司 | 一种硼替佐米中间体及其制备方法和应用 |
| US10022372B2 (en) | 2013-04-19 | 2018-07-17 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
| MA39964A (fr) | 2014-05-20 | 2015-11-26 | Millennium Pharm Inc | Inhibiteurs du protéasome contenant du bore destinés à être utilisés après une thérapie contre le cancer primaire |
| EP3778584A1 (en) | 2014-06-19 | 2021-02-17 | ARIAD Pharmaceuticals, Inc. | Production process of 2-chloro-4-heteroaryl-pyrimidine derivatives |
| MA41505A (fr) | 2015-02-11 | 2017-12-19 | Millennium Pharm Inc | Nouvelle forme cristalline d'un inhibiteur de protéasome |
| PL3472149T3 (pl) | 2016-06-21 | 2024-02-12 | Orion Ophthalmology LLC | Heterocykliczne pochodne prolinamidu |
| US10526315B2 (en) | 2016-06-21 | 2020-01-07 | Orion Ophthalmology LLC | Carbocyclic prolinamide derivatives |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4499082A (en) | 1983-12-05 | 1985-02-12 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid peptides |
| EP0315574A3 (de) | 1987-11-05 | 1990-08-22 | Hoechst Aktiengesellschaft | Renin-Inhibitoren |
| US5106948A (en) * | 1988-05-27 | 1992-04-21 | Mao Foundation For Medical Education And Research | Cytotoxic boronic acid peptide analogs |
| GB9017694D0 (en) | 1990-08-13 | 1990-09-26 | Sandoz Ltd | Improvements in or relating to organic chemistry |
| US5384410A (en) | 1993-03-24 | 1995-01-24 | The Du Pont Merck Pharmaceutical Company | Removal of boronic acid protecting groups by transesterification |
| US5658885A (en) | 1993-04-27 | 1997-08-19 | The Dupont Merck Pharmaceutical Company | Amidino and guanidino substituted boronic acid inhibitors of trypsin-like enzymes |
| IL109319A0 (en) | 1993-04-27 | 1994-07-31 | Du Pont Merck Pharma | Amidino and guanidino substituted boronic acid compounds |
| FR2721611B1 (fr) * | 1994-06-22 | 1996-09-27 | Adir | Nouveaux dérivés peptidiques de l'acide boronique, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent . |
| US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| US5550262A (en) | 1994-11-14 | 1996-08-27 | Cephalon, Inc. | Multicatalytic protease inhibitors |
| US5614649A (en) | 1994-11-14 | 1997-03-25 | Cephalon, Inc. | Multicatalytic protease inhibitors |
| CA2314259A1 (en) | 1997-12-16 | 1999-06-24 | Robert Siman | Multicatalytic protease inhibitors for use as anti-tumor agents |
| WO2002096933A1 (en) * | 2001-05-30 | 2002-12-05 | Novartis Ag | 2-{[n-(2-amino-3-(heteroaryl or aryl)propionyl)-aminoacyl]-amino}-alkylboronic acid derivatives |
-
2002
- 2002-05-29 WO PCT/EP2002/005937 patent/WO2002096933A1/en not_active Ceased
- 2002-05-29 CA CA002446282A patent/CA2446282A1/en not_active Abandoned
- 2002-05-29 JP JP2003500112A patent/JP4416501B2/ja not_active Expired - Fee Related
- 2002-05-29 DE DE60209227T patent/DE60209227T2/de not_active Expired - Fee Related
- 2002-05-29 AT AT02743128T patent/ATE317850T1/de not_active IP Right Cessation
- 2002-05-29 US US10/478,794 patent/US6933290B2/en not_active Expired - Fee Related
- 2002-05-29 CN CNB028108132A patent/CN100415770C/zh not_active Expired - Fee Related
- 2002-05-29 PT PT02743128T patent/PT1399468E/pt unknown
- 2002-05-29 EP EP02743128A patent/EP1399468B1/en not_active Expired - Lifetime
- 2002-05-29 BR BR0210112-2A patent/BR0210112A/pt not_active IP Right Cessation
- 2002-05-29 ES ES02743128T patent/ES2258149T3/es not_active Expired - Lifetime
-
2005
- 2005-06-30 US US11/172,146 patent/US20050239716A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| PT1399468E (pt) | 2006-05-31 |
| US20040167337A1 (en) | 2004-08-26 |
| CN100415770C (zh) | 2008-09-03 |
| JP2005501005A (ja) | 2005-01-13 |
| EP1399468A1 (en) | 2004-03-24 |
| CN1512999A (zh) | 2004-07-14 |
| US6933290B2 (en) | 2005-08-23 |
| DE60209227D1 (de) | 2006-04-20 |
| BR0210112A (pt) | 2004-06-08 |
| WO2002096933A1 (en) | 2002-12-05 |
| ES2258149T3 (es) | 2006-08-16 |
| JP4416501B2 (ja) | 2010-02-17 |
| EP1399468B1 (en) | 2006-02-15 |
| US20050239716A1 (en) | 2005-10-27 |
| ATE317850T1 (de) | 2006-03-15 |
| DE60209227T2 (de) | 2006-08-17 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |