JP2000504023A - 癌治療方法 - Google Patents

癌治療方法

Info

Publication number: JP2000504023A
Authority: JP; Japan
Prior art keywords: alkyl; glycyl; ylmethyl; substituted; methionine
Prior art date: 1996-04-03
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.): Pending

Application number

JP9535542A

Other languages

English (en)

Japanese (ja)

Inventor

ヘイムブルツク，デイビツド・シイ

オリフ，アレン・アイ

ステイルデイバント，ステーイブン・エム

Original Assignee

メルクエンドカンパニーインコーポレーテッド

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-04-03

Filing date

1997-03-31

Publication date

2000-04-04

1996-06-28 Priority claimed from GBGB9613599.1A external-priority patent/GB9613599D0/en

1997-03-31 Application filed by メルクエンドカンパニーインコーポレーテッド filed Critical メルクエンドカンパニーインコーポレーテッド

2000-04-04 Publication of JP2000504023A publication Critical patent/JP2000504023A/ja

Status Pending legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 66
206010028980 Neoplasm Diseases 0.000 title claims abstract description 38
201000011510 cancer Diseases 0.000 title claims abstract description 26
150000001875 compounds Chemical class 0.000 claims abstract description 198
102000004357 Transferases Human genes 0.000 claims abstract description 17
108090000992 Transferases Proteins 0.000 claims abstract description 17
125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 16
-1 1-imidazolyl Chemical group 0.000 claims description 357
125000003118 aryl group Chemical group 0.000 claims description 313
125000000623 heterocyclic group Chemical group 0.000 claims description 299
239000001257 hydrogen Substances 0.000 claims description 165
229910052739 hydrogen Inorganic materials 0.000 claims description 165
125000000753 cycloalkyl group Chemical group 0.000 claims description 149
125000000217 alkyl group Chemical group 0.000 claims description 113
150000002431 hydrogen Chemical class 0.000 claims description 96
229910052794 bromium Inorganic materials 0.000 claims description 73
229910052801 chlorine Inorganic materials 0.000 claims description 73
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 70
150000003839 salts Chemical class 0.000 claims description 70
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 67
229910052731 fluorine Inorganic materials 0.000 claims description 61
229910052757 nitrogen Inorganic materials 0.000 claims description 57
125000001424 substituent group Chemical group 0.000 claims description 53
125000001072 heteroaryl group Chemical group 0.000 claims description 44
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 42
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 40
125000003107 substituted aryl group Chemical group 0.000 claims description 38
229910052717 sulfur Inorganic materials 0.000 claims description 38
150000001413 amino acids Chemical group 0.000 claims description 37
229910052760 oxygen Inorganic materials 0.000 claims description 34
229920006395 saturated elastomer Polymers 0.000 claims description 34
125000003342 alkenyl group Chemical group 0.000 claims description 31
QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 claims description 30
UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 claims description 30
QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 claims description 30
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 30
239000002253 acid Substances 0.000 claims description 28
PFMUCCYYAAFKTH-YFKPBYRVSA-N Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CN PFMUCCYYAAFKTH-YFKPBYRVSA-N 0.000 claims description 27
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 25
125000004429 atom Chemical group 0.000 claims description 25
235000004279 alanine Nutrition 0.000 claims description 22
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 21
125000005843 halogen group Chemical group 0.000 claims description 21
125000005842 heteroatom Chemical group 0.000 claims description 20
125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 20
125000006239 protecting group Chemical group 0.000 claims description 20
229910052720 vanadium Inorganic materials 0.000 claims description 20
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 claims description 18
IPSFOLSLIUIMKK-LURJTMIESA-N methyl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@@H](C(=O)OC)NC(=O)CN IPSFOLSLIUIMKK-LURJTMIESA-N 0.000 claims description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 14
239000005557 antagonist Substances 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 13
125000003710 aryl alkyl group Chemical group 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
150000002148 esters Chemical class 0.000 claims description 13
230000002401 inhibitory effect Effects 0.000 claims description 13
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 12
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
239000011593 sulfur Substances 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
239000003610 charcoal Substances 0.000 claims description 11
125000004122 cyclic group Chemical group 0.000 claims description 11
150000004702 methyl esters Chemical class 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
238000006467 substitution reaction Methods 0.000 claims description 10
150000001721 carbon Chemical group 0.000 claims description 9
229930182817 methionine Natural products 0.000 claims description 9
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 8
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
125000002950 monocyclic group Chemical group 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
229940016590 sarkosyl Drugs 0.000 claims description 8
108700004121 sarkosyl Proteins 0.000 claims description 8
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 8
XBZOQGHZGQLEQO-IUCAKERBSA-N Lys-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCCN XBZOQGHZGQLEQO-IUCAKERBSA-N 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
BNUFZLNMGFEGNS-ZCYQVOJMSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 BNUFZLNMGFEGNS-ZCYQVOJMSA-N 0.000 claims description 6
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
102000007317 Farnesyltranstransferase Human genes 0.000 claims description 6
108010007508 Farnesyltranstransferase Proteins 0.000 claims description 6
ZDXPYRJPNDTMRX-UHFFFAOYSA-N Glutamine Chemical compound OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
125000002619 bicyclic group Chemical group 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 claims description 6
229960002195 perazine Drugs 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000000547 substituted alkyl group Chemical group 0.000 claims description 6
KRDCKLXYBSFBNW-VWLOTQADSA-N 4-[[5-[[(2s)-2-butyl-4-(2,3-dimethylphenyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1CCCC)N(C=2C(=C(C)C=CC=2)C)C(=O)CN1CC1=CN=CN1CC1=CC=C(C#N)C=C1 KRDCKLXYBSFBNW-VWLOTQADSA-N 0.000 claims description 5
241001024304 Mino Species 0.000 claims description 5
125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 5
150000002460 imidazoles Chemical class 0.000 claims description 5
239000002932 luster Substances 0.000 claims description 5
PRGUXYFOEDWESW-QMMMGPOBSA-N propan-2-yl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@H](NC(=O)CN)C(=O)OC(C)C PRGUXYFOEDWESW-QMMMGPOBSA-N 0.000 claims description 5
WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 5
125000006413 ring segment Chemical group 0.000 claims description 5
KKKDZZRICRFGSD-UHFFFAOYSA-N 1-benzylimidazole Chemical compound C1=CN=CN1CC1=CC=CC=C1 KKKDZZRICRFGSD-UHFFFAOYSA-N 0.000 claims description 4
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 4
QVELSCNTBHCXNR-MHZLTWQESA-N 4-[[5-[[(2s)-2-butyl-4-(naphthalene-1-carbonyl)piperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(C#N)C=C1 QVELSCNTBHCXNR-MHZLTWQESA-N 0.000 claims description 4
RMZQNOARFIICNW-DEOSSOPVSA-N 4-[[5-[[(2s)-4-(2,3-dimethylphenyl)-2-(2-methoxyethyl)-5-oxopiperazin-1-yl]methyl]imidazol-1-yl]methyl]benzonitrile Chemical compound C([C@@H]1CCOC)N(C=2C(=C(C)C=CC=2)C)C(=O)CN1CC1=CN=CN1CC1=CC=C(C#N)C=C1 RMZQNOARFIICNW-DEOSSOPVSA-N 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
241000764238 Isis Species 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
KZFMVLBRWLEDLF-SANMLTNESA-N [(3s)-3-butyl-4-[[3-[(4-chlorophenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(Cl)C=C1 KZFMVLBRWLEDLF-SANMLTNESA-N 0.000 claims description 4
125000003435 aroyl group Chemical group 0.000 claims description 4
125000005002 aryl methyl group Chemical group 0.000 claims description 4
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 4
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
DFNPCBBBVQMXBS-STQMWFEESA-N propan-2-yl (2s)-2-[[(2s)-1-ethylpyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoate Chemical compound CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)OC(C)C DFNPCBBBVQMXBS-STQMWFEESA-N 0.000 claims description 4
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
BYFYEZSVEJKKFR-CAIZAGQASA-N (2s)-2-[[(2s,3s)-3-ethyl-1-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H]1[C@@H](CC)CCN1C[C@H]1N(C(=O)CC=2N=CNC=2)CCC1 BYFYEZSVEJKKFR-CAIZAGQASA-N 0.000 claims description 3
XNLSOFWOAJBPRW-SFTDATJTSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(2-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC=C1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@H]1N(C(=O)CC=2NC=NC=2)CCC1 XNLSOFWOAJBPRW-SFTDATJTSA-N 0.000 claims description 3
ZBBSQXCFADEMLA-XWGVYQGASA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCC(=O)N1 ZBBSQXCFADEMLA-XWGVYQGASA-N 0.000 claims description 3
JTHYTTAMRPUVFT-BDYUSTAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 JTHYTTAMRPUVFT-BDYUSTAISA-N 0.000 claims description 3
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 3
125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 3
206010006187 Breast cancer Diseases 0.000 claims description 3
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
206010041067 Small cell lung cancer Diseases 0.000 claims description 3
108010076830 Thionins Proteins 0.000 claims description 3
RTVOEPCPPNTPRP-NRFANRHFSA-N [(3s)-3-butyl-4-(2-imidazol-1-ylethylsulfonyl)piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1S(=O)(=O)CCN1C=CN=C1 RTVOEPCPPNTPRP-NRFANRHFSA-N 0.000 claims description 3
OLSVEEWCYNTQJD-LJAQVGFWSA-N [(3s)-3-butyl-4-[[3-(naphthalen-1-ylmethyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC=3N(C=NC=3)CC=3C4=CC=CC=C4C=CC=3)CCCC)=CC=CC2=C1 OLSVEEWCYNTQJD-LJAQVGFWSA-N 0.000 claims description 3
JSWSSUDGMFUBPM-MHZLTWQESA-N [(3s)-3-butyl-4-[[3-[(3-methylphenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=CC(C)=C1 JSWSSUDGMFUBPM-MHZLTWQESA-N 0.000 claims description 3
ATICIZQVYXZRKE-SANMLTNESA-N [(3s)-3-butyl-4-[[3-[(4-fluorophenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(F)C=C1 ATICIZQVYXZRKE-SANMLTNESA-N 0.000 claims description 3
QHKXREACPVGZHL-SANMLTNESA-N [(3s)-3-butyl-4-[[3-[(4-methoxyphenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(OC)C=C1 QHKXREACPVGZHL-SANMLTNESA-N 0.000 claims description 3
LJCGCTKDZDSLPX-YTTGMZPUSA-N [(3s)-3-butyl-4-[[3-[(4-phenylphenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC(C=C1)=CC=C1C1=CC=CC=C1 LJCGCTKDZDSLPX-YTTGMZPUSA-N 0.000 claims description 3
OITGWZQOTKBNHC-MHAHJAEUSA-N [(3s)-4-[(2r)-2-amino-3-hydroxyheptadecyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1[C@H](CCCC)N(C[C@@H](N)C(O)CCCCCCCCCCCCCC)CCN1C(=O)C1=CC=CC2=CC=CC=C12 OITGWZQOTKBNHC-MHAHJAEUSA-N 0.000 claims description 3
IVFJZZVFLCGKMR-MOPGFXCFSA-N [(3s)-4-[(2r)-2-amino-3-hydroxypropyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1CN(C[C@@H](N)CO)[C@@H](CCCC)CN1C(=O)C1=CC=CC2=CC=CC=C12 IVFJZZVFLCGKMR-MOPGFXCFSA-N 0.000 claims description 3
SFMJVGMTFJODNJ-CGAIIQECSA-N [(3s)-4-[2-amino-3-(2-hydroxyphenyl)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC(N)CC1=CC=CC=C1O SFMJVGMTFJODNJ-CGAIIQECSA-N 0.000 claims description 3
QDVKETOAAQPNNT-ZSXSBBPPSA-N [(3s)-4-[3-amino-2-(naphthalen-2-ylmethylamino)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC(CN)NCC=3C=C4C=CC=CC4=CC=3)CCCC)=CC=CC2=C1 QDVKETOAAQPNNT-ZSXSBBPPSA-N 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
210000000867 larynx Anatomy 0.000 claims description 3
201000005249 lung adenocarcinoma Diseases 0.000 claims description 3
IRYTXZYSQWNLMJ-AHWVRZQESA-N methyl (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 IRYTXZYSQWNLMJ-AHWVRZQESA-N 0.000 claims description 3
KSRIGEDVURVPEB-XCZPVHLTSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 KSRIGEDVURVPEB-XCZPVHLTSA-N 0.000 claims description 3
STTPMEVACJNPEF-YADHBBJMSA-N n-[[(2r)-2-amino-3-[(2s)-2-butyl-4-(naphthalene-1-carbonyl)piperazin-1-yl]propyl]sulfanylmethyl]acetamide Chemical compound C1CN(C[C@@H](N)CSCNC(C)=O)[C@@H](CCCC)CN1C(=O)C1=CC=CC2=CC=CC=C12 STTPMEVACJNPEF-YADHBBJMSA-N 0.000 claims description 3
229910052698 phosphorus Inorganic materials 0.000 claims description 3
239000006187 pill Substances 0.000 claims description 3
ALSVYJWYFHSURP-JDXGNMNLSA-N propan-2-yl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-4-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)C)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=NC=C1 ALSVYJWYFHSURP-JDXGNMNLSA-N 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
CLNGMCHUKJFCQJ-UHFFFAOYSA-N tert-butyl 3-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 CLNGMCHUKJFCQJ-UHFFFAOYSA-N 0.000 claims description 3
PIIVKCJYOUJKQK-GOTSBHOMSA-N (2S)-4-methylsulfanyl-2-[3-phenylpropanoyl-[[(2S)-1-(pyridin-3-ylmethyl)pyrrolidin-2-yl]methoxy]amino]butanoic acid Chemical compound C([C@H]1CON([C@@H](CCSC)C(O)=O)C(=O)CCC=2C=CC=CC=2)CCN1CC1=CC=CN=C1 PIIVKCJYOUJKQK-GOTSBHOMSA-N 0.000 claims description 2
WMLVYMSANAXLFU-QABMSTFYSA-N (2r)-5-amino-2-(dimethylamino)-2-[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]-5-oxopentanoic acid Chemical compound C([C@H]1CN(CC(=O)[C@](CCC(N)=O)(C(O)=O)N(C)C)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 WMLVYMSANAXLFU-QABMSTFYSA-N 0.000 claims description 2
CDNYGEBAKLWIHE-GOTSBHOMSA-N (2s)-2-[[2-[(2-cyanophenyl)methyl-[[(2s)-1-[3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C(=CC=CC=2)C#N)CCN1C(=O)CCC1=CNC=N1 CDNYGEBAKLWIHE-GOTSBHOMSA-N 0.000 claims description 2
JMEPRQNCQFXREP-VXKWHMMOSA-N (2s)-2-[[2-[(3-cyanophenyl)methyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C=C(C=CC=2)C#N)CCN1C(=O)CC1=CN=CN1 JMEPRQNCQFXREP-VXKWHMMOSA-N 0.000 claims description 2
LDUJEEUZBDBLJF-VXKWHMMOSA-N (2s)-2-[[2-[(4-cyanophenyl)methyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C=CC(=CC=2)C#N)CCN1C(=O)CC1=CN=CN1 LDUJEEUZBDBLJF-VXKWHMMOSA-N 0.000 claims description 2
VOWJQSVTTNCIGG-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-(1h-imidazole-5-carbonyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1=CNC=N1 VOWJQSVTTNCIGG-GMAHTHKFSA-N 0.000 claims description 2
BBIMPJDOEHPCLJ-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-(2-aminoethyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1CCN BBIMPJDOEHPCLJ-GMAHTHKFSA-N 0.000 claims description 2
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NIMQYCGHXAABQY-DMDYGQEQSA-N (2s)-2-[[2-[[(2s)-1-[(2r)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=1C2=CC=CC=C2C=CC=1)C1=CNC=N1 NIMQYCGHXAABQY-DMDYGQEQSA-N 0.000 claims description 2
RDGVOABWUWODLX-JZWVFAODSA-N (2s)-2-[[2-[[(2s)-1-[(2r)-2-aminopropanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)[C@@H](C)N RDGVOABWUWODLX-JZWVFAODSA-N 0.000 claims description 2
RURORQLXYNJSAS-XWGVYQGASA-N (2s)-2-[[2-[[(2s)-1-[(2s)-2,5-diamino-5-oxopentanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O RURORQLXYNJSAS-XWGVYQGASA-N 0.000 claims description 2
NIMQYCGHXAABQY-RNXOBYDBSA-N (2s)-2-[[2-[[(2s)-1-[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=1C2=CC=CC=C2C=CC=1)C1=CNC=N1 NIMQYCGHXAABQY-RNXOBYDBSA-N 0.000 claims description 2
HUBAHCJBIRMDBS-PMVMPFDFSA-N (2s)-2-[[2-[[(2s)-1-[(3s)-3,4-diamino-4-oxobutanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)C[C@H](N)C(N)=O HUBAHCJBIRMDBS-PMVMPFDFSA-N 0.000 claims description 2
IYOYWOOGHIFUGV-VXKWHMMOSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(2-methylphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C(=CC=CC=2)C)CCN1C(=O)CC1=CN=CN1 IYOYWOOGHIFUGV-VXKWHMMOSA-N 0.000 claims description 2
NAPKHUSBDHTYQA-UNMCSNQZSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[(3-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC(CN(C[C@H]2N(CCC2)C(=O)CC=2NC=NC=2)CC(=O)N[C@@H](CCSC)C(O)=O)=C1 NAPKHUSBDHTYQA-UNMCSNQZSA-N 0.000 claims description 2
XQGBKKUAEDGZFI-GMAHTHKFSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-naphthalen-1-ylsulfonylamino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)S(=O)(=O)C=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 XQGBKKUAEDGZFI-GMAHTHKFSA-N 0.000 claims description 2
NSTOSYAYHNCROE-UPVQGACJSA-N (2s)-2-[[2-[[(2s)-1-[2-(dimethylamino)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@@H]1CCCN1C(=O)CN(C)C NSTOSYAYHNCROE-UPVQGACJSA-N 0.000 claims description 2
LRICZMUKYVXXAT-VXKWHMMOSA-N (2s)-2-[[2-[[(2s)-1-[3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-[(2-methoxyphenyl)methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound COC1=CC=CC=C1CN(CC(=O)N[C@@H](CCSC)C(O)=O)C[C@H]1N(C(=O)CCC=2N=CNC=2)CCC1 LRICZMUKYVXXAT-VXKWHMMOSA-N 0.000 claims description 2
LLWHJERHFOWCKW-BDYUSTAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-2-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CC=N1 LLWHJERHFOWCKW-BDYUSTAISA-N 0.000 claims description 2
XGBRPDFOFRPDJH-BDYUSTAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-3-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CN=C1 XGBRPDFOFRPDJH-BDYUSTAISA-N 0.000 claims description 2
KZMFHSMLMMKVBK-AHWVRZQESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-4-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCNCC1 KZMFHSMLMMKVBK-AHWVRZQESA-N 0.000 claims description 2
BVVYOFGYTQLBKT-HVCNVCAESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-pyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCCN1 BVVYOFGYTQLBKT-HVCNVCAESA-N 0.000 claims description 2
YRSFPIMTLHOOHE-AHWVRZQESA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-2-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=CC=N1 YRSFPIMTLHOOHE-AHWVRZQESA-N 0.000 claims description 2
125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 2
RQFOMRXULVGANJ-UHFFFAOYSA-N 2-[3-[4-[4-(3,4-dichlorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidin-1-yl]propyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCN(CCCN3S(C4=CC=CC=C4C3=O)(=O)=O)CC2)N1 RQFOMRXULVGANJ-UHFFFAOYSA-N 0.000 claims description 2
PCUYSQDVWMRTAO-UHFFFAOYSA-N 2-[3-[4-[4-(3,4-dichlorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidin-1-yl]propyl]isoindole-1,3-dione Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCN(CCCN3C(C4=CC=CC=C4C3=O)=O)CC2)N1 PCUYSQDVWMRTAO-UHFFFAOYSA-N 0.000 claims description 2
RKYNIUIPMRFVJX-UHFFFAOYSA-N 2-[5-[4-[4-(3,4-dichlorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidin-1-yl]pentyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCN(CCCCCN3S(C4=CC=CC=C4C3=O)(=O)=O)CC2)N1 RKYNIUIPMRFVJX-UHFFFAOYSA-N 0.000 claims description 2
CLKUHLXHUUSWIC-UHFFFAOYSA-N 2-[5-[4-[4-(3,4-dichlorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidin-1-yl]pentyl]isoindole-1,3-dione Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCN(CCCCCN3C(C4=CC=CC=C4C3=O)=O)CC2)N1 CLKUHLXHUUSWIC-UHFFFAOYSA-N 0.000 claims description 2
GYGGXCNUQIYXAV-UHFFFAOYSA-N 2-[6-[4-[4-(3,4-dichlorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidin-1-yl]hexyl]-1,1-dioxo-1,2-benzothiazol-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCN(CCCCCCN3S(C4=CC=CC=C4C3=O)(=O)=O)CC2)N1 GYGGXCNUQIYXAV-UHFFFAOYSA-N 0.000 claims description 2
125000006494 2-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 claims description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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HBLDNAVQCOHUEH-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-(3-methylsulfonylphenyl)-1h-imidazol-5-yl]pyridine Chemical compound CS(=O)(=O)C1=CC=CC(C=2NC(=C(N=2)C=2C=CC(F)=CC=2)C=2C=CN=CC=2)=C1 HBLDNAVQCOHUEH-UHFFFAOYSA-N 0.000 claims description 2
XBOAMGVRMOKHNU-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-(4-methoxyphenyl)-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(OC)=CC=C1C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 XBOAMGVRMOKHNU-UHFFFAOYSA-N 0.000 claims description 2
IXHWMGAFLNPNII-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-piperidin-4-yl-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C2CCNCC2)N1 IXHWMGAFLNPNII-UHFFFAOYSA-N 0.000 claims description 2
208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
GTHRHKIKXGVIOH-MQWKRIRWSA-N C(C(O)CO)OC([C@@H](NC(CN)=O)CCSC)=O Chemical compound C(C(O)CO)OC([C@@H](NC(CN)=O)CCSC)=O GTHRHKIKXGVIOH-MQWKRIRWSA-N 0.000 claims description 2
UUGYBWICSROEIS-LBPRGKRZSA-N C(C1=CC=CC=C1)OC([C@@H](NC(CN)=O)CCSC)=O Chemical compound C(C1=CC=CC=C1)OC([C@@H](NC(CN)=O)CCSC)=O UUGYBWICSROEIS-LBPRGKRZSA-N 0.000 claims description 2
NYVYNBDQPXBKJQ-NSHDSACASA-N C1(CCCCC1)OC([C@@H](NC(CN)=O)CCSC)=O Chemical compound C1(CCCCC1)OC([C@@H](NC(CN)=O)CCSC)=O NYVYNBDQPXBKJQ-NSHDSACASA-N 0.000 claims description 2
YQEOSBANZFCHDL-JTQLQIEISA-N CCC(CC)OC(=O)[C@H](CCSC)NC(=O)CN Chemical compound CCC(CC)OC(=O)[C@H](CCSC)NC(=O)CN YQEOSBANZFCHDL-JTQLQIEISA-N 0.000 claims description 2
LXHVDHCVOHXJTE-UWVGGRQHSA-N CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(O)=O Chemical compound CCN1CCC[C@H]1C(=O)N[C@@H](CCSC)C(O)=O LXHVDHCVOHXJTE-UWVGGRQHSA-N 0.000 claims description 2
UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims description 2
PVYWVOMHDKGWBJ-QFIPXVFZSA-N [(3s)-3-butyl-4-[3-(1h-imidazol-5-yl)propyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CCCC1=CNC=N1 PVYWVOMHDKGWBJ-QFIPXVFZSA-N 0.000 claims description 2
AEKIOMXHUIEHTI-PMERELPUSA-N [(3s)-3-butyl-4-[[3-(naphthalen-2-ylmethyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C1=CC=C2C(C(=O)N3C[C@@H](N(CC3)CC=3N(C=NC=3)CC=3C=C4C=CC=CC4=CC=3)CCCC)=CC=CC2=C1 AEKIOMXHUIEHTI-PMERELPUSA-N 0.000 claims description 2
WLDBTADIHZYGKF-MHZLTWQESA-N [(3s)-3-butyl-4-[[3-[(4-methylphenyl)methyl]imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC1=CC=C(C)C=C1 WLDBTADIHZYGKF-MHZLTWQESA-N 0.000 claims description 2
AVXFQBJAVCGIFW-FLDQDSGZSA-N [(3s)-4-[2-amino-3-(2-phenylmethoxyphenyl)propyl]-3-butylpiperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC(N)CC1=CC=CC=C1OCC1=CC=CC=C1 AVXFQBJAVCGIFW-FLDQDSGZSA-N 0.000 claims description 2
125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 2
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
150000001768 cations Chemical class 0.000 claims description 2
125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
ZBKUMGBVZLQGRO-ZETCQYMHSA-N ethyl (2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoate Chemical compound CCOC(=O)[C@H](CCSC)NC(=O)CN ZBKUMGBVZLQGRO-ZETCQYMHSA-N 0.000 claims description 2
125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 2
210000004185 liver Anatomy 0.000 claims description 2
210000004072 lung Anatomy 0.000 claims description 2
210000004324 lymphatic system Anatomy 0.000 claims description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
VZDCSCPXWAKUJU-VXKWHMMOSA-N methyl (2S)-2-[[(2S)-1-[2-(1H-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methoxy-(3-phenylpropanoyl)amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CON([C@@H](CCSC)C(=O)OC)C(=O)CCC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 VZDCSCPXWAKUJU-VXKWHMMOSA-N 0.000 claims description 2
JCUQPOFQFDSTBG-VVFBEHOQSA-N methyl (2r)-5-amino-2-(dimethylamino)-2-[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]-5-oxopentanoate Chemical compound C([C@H]1CN(CC(=O)[C@@](CCC(N)=O)(N(C)C)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 JCUQPOFQFDSTBG-VVFBEHOQSA-N 0.000 claims description 2
BULHVUSANBRPQC-WBKMXMRLSA-N methyl (2s)-2-[[(2s,3s)-3-ethyl-1-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@@H](C(=O)OC)NC(=O)[C@@H]1[C@@H](CC)CCN1C[C@H]1N(C(=O)CC=2N=CNC=2)CCC1 BULHVUSANBRPQC-WBKMXMRLSA-N 0.000 claims description 2
XTEQPZARJCTXPJ-ZEQRLZLVSA-N methyl (2s)-2-[[2-[(2-cyanophenyl)methyl-[[(2s)-1-[3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C(=CC=CC=2)C#N)CCN1C(=O)CCC1=CNC=N1 XTEQPZARJCTXPJ-ZEQRLZLVSA-N 0.000 claims description 2
XBHIDWKJAGFKQB-UPVQGACJSA-N methyl (2s)-2-[[2-[[(2s)-1-(1h-imidazole-5-carbonyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1=CNC=N1 XBHIDWKJAGFKQB-UPVQGACJSA-N 0.000 claims description 2
KKHKWUHYSPSTGC-OIKPOIBNSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2r)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)C1=CN=CN1 KKHKWUHYSPSTGC-OIKPOIBNSA-N 0.000 claims description 2
NGXKPLLTHVOWOD-UCFCWBNQSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2r)-2-aminopropanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)[C@@H](C)N NGXKPLLTHVOWOD-UCFCWBNQSA-N 0.000 claims description 2
YOXZXGNNGZYPKQ-YTMVLYRLSA-N methyl (2s)-2-[[2-[[(2s)-1-[2-[methyl(pyridin-4-yl)amino]acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CN(C)C1=CC=NC=C1 YOXZXGNNGZYPKQ-YTMVLYRLSA-N 0.000 claims description 2
IDOPLSXAMKHPEG-VXKWHMMOSA-N methyl (2s)-2-[[2-[benzyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 IDOPLSXAMKHPEG-VXKWHMMOSA-N 0.000 claims description 2
BPSHEPGKEMZQEO-ZEQRLZLVSA-N methyl (2s)-4-methylsulfanyl-2-[3-phenylpropanoyl-[[(2s)-1-(pyridin-3-ylmethyl)pyrrolidin-2-yl]methoxy]amino]butanoate Chemical compound C([C@H]1CON([C@@H](CCSC)C(=O)OC)C(=O)CCC=2C=CC=CC=2)CCN1CC1=CC=CN=C1 BPSHEPGKEMZQEO-ZEQRLZLVSA-N 0.000 claims description 2
LMWZXKDVEIHYSV-XCZPVHLTSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-2-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CC=N1 LMWZXKDVEIHYSV-XCZPVHLTSA-N 0.000 claims description 2
NKHUVKYFYROPGF-XCZPVHLTSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(2-pyridin-3-ylacetyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CC=CN=C1 NKHUVKYFYROPGF-XCZPVHLTSA-N 0.000 claims description 2
PQHPNFNTLZVBKS-ZVNMQXQGSA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-3-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCCNC1 PQHPNFNTLZVBKS-ZVNMQXQGSA-N 0.000 claims description 2
ZPSOILKVHRWGCY-HVCNVCAESA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)[C@@H]1CCC(=O)N1 ZPSOILKVHRWGCY-HVCNVCAESA-N 0.000 claims description 2
NJXNJEFBSMAYQB-BDYUSTAISA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-[2-(pyridin-2-ylamino)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CNC1=CC=CC=N1 NJXNJEFBSMAYQB-BDYUSTAISA-N 0.000 claims description 2
RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
201000002528 pancreatic cancer Diseases 0.000 claims description 2
208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
RVJFYCFGCRETAZ-BDYUSTAISA-N propan-2-yl (2s)-2-[[2-[[(2s)-1-[2-(dimethylamino)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)C)C[C@@H]1CCCN1C(=O)CN(C)C RVJFYCFGCRETAZ-BDYUSTAISA-N 0.000 claims description 2
125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 2
125000005493 quinolyl group Chemical group 0.000 claims description 2
210000002784 stomach Anatomy 0.000 claims description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
IMTGKHVDTDPVRV-UHFFFAOYSA-N tert-butyl 4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 IMTGKHVDTDPVRV-UHFFFAOYSA-N 0.000 claims description 2
125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
229910052727 yttrium Inorganic materials 0.000 claims description 2
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
SNJMJAVKVFZWSV-ZCYQVOJMSA-N (2s)-2-[[2-[[(2s)-1-(1h-imidazol-5-ylmethyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1CC1=CNC=N1 SNJMJAVKVFZWSV-ZCYQVOJMSA-N 0.000 claims 1
ZSUOHOMDEQTSSS-FPOVZHCZSA-N (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-[[2-(trifluoromethyl)phenyl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C(=CC=CC=2)C(F)(F)F)CCN1C(=O)CC1=CNC=N1 ZSUOHOMDEQTSSS-FPOVZHCZSA-N 0.000 claims 1
PJIRHLLXQXEKHG-SFTDATJTSA-N (2s)-2-[[2-[benzyl-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl]amino]acetyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C=CC=CC=2)CCN1C(=O)CC1=CN=CN1 PJIRHLLXQXEKHG-SFTDATJTSA-N 0.000 claims 1
UQSVTVHBYSCUOS-INIZCTEOSA-N (2s)-4-methylsulfanyl-2-[[2-(naphthalen-1-ylmethylamino)acetyl]amino]butanoic acid Chemical compound C1=CC=C2C(CNCC(=O)N[C@@H](CCSC)C(O)=O)=CC=CC2=C1 UQSVTVHBYSCUOS-INIZCTEOSA-N 0.000 claims 1
HFABAVNVKIGOQD-MMOCMJAISA-N (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-3-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoic acid Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(O)=O)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCCNC1 HFABAVNVKIGOQD-MMOCMJAISA-N 0.000 claims 1
MLLJGMFEGRJXLX-UHFFFAOYSA-N 4-[2-(4-methylsulfanylphenyl)-5-naphthalen-1-yl-1h-imidazol-4-yl]pyridine Chemical compound C1=CC(SC)=CC=C1C1=NC(C=2C=CN=CC=2)=C(C=2C3=CC=CC=C3C=CC=2)N1 MLLJGMFEGRJXLX-UHFFFAOYSA-N 0.000 claims 1
POUDZVWQMHMTCJ-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-(1-methylpiperidin-3-yl)-1h-imidazol-5-yl]pyridine Chemical compound C1N(C)CCCC1C1=NC(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)N1 POUDZVWQMHMTCJ-UHFFFAOYSA-N 0.000 claims 1
LFPRICXNGTVKHB-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-methyl-2-(4-methylsulfinylphenyl)imidazol-4-yl]pyridine Chemical compound CN1C(C=2C=CC(=CC=2)S(C)=O)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=NC=C1 LFPRICXNGTVKHB-UHFFFAOYSA-N 0.000 claims 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 1
208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 1
SUNRCDSJBVJKOF-DEOSSOPVSA-N [(3s)-3-butyl-4-[[3-(3-methylbut-2-enyl)imidazol-4-yl]methyl]piperazin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1CCCC)N(C(=O)C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CN=CN1CC=C(C)C SUNRCDSJBVJKOF-DEOSSOPVSA-N 0.000 claims 1
OMJJXOGARPFMJT-UPVQGACJSA-N methyl (2s)-2-[[2-[[(2s)-1-(3-aminopropanoyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)CCN OMJJXOGARPFMJT-UPVQGACJSA-N 0.000 claims 1
MVEXQFGXLMPEIZ-HVCNVCAESA-N methyl (2s)-2-[[2-[[(2s)-1-[(2s)-2,5-diamino-5-oxopentanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O MVEXQFGXLMPEIZ-HVCNVCAESA-N 0.000 claims 1
KKHKWUHYSPSTGC-URORMMCBSA-N methyl (2s)-2-[[2-[[(2s)-1-[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)C1=CN=CN1 KKHKWUHYSPSTGC-URORMMCBSA-N 0.000 claims 1
HQFUINJGHRJKJL-DPGDXNODSA-N methyl (2s)-2-[[2-[[(2s,3s)-2-[[2-[3-[(4-cyanophenyl)methyl]imidazol-4-yl]acetyl]amino]-3-methylpentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound N([C@H](CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)[C@@H](C)CC)C(=O)CC1=CN=CN1CC1=CC=C(C#N)C=C1 HQFUINJGHRJKJL-DPGDXNODSA-N 0.000 claims 1
SBVVZLWMKBDEEF-BDYUSTAISA-N methyl (2s)-4-methylsulfanyl-2-[[2-[naphthalen-1-ylmethyl-[[(2s)-1-(piperidine-4-carbonyl)pyrrolidin-2-yl]methyl]amino]acetyl]amino]butanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)C1CCNCC1 SBVVZLWMKBDEEF-BDYUSTAISA-N 0.000 claims 1
ZYXVFHLTYWMIHA-ZCYQVOJMSA-N propan-2-yl (2s)-2-[[2-[[(2s)-1-(2-aminoacetyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)C)C[C@@H]1CCCN1C(=O)CN ZYXVFHLTYWMIHA-ZCYQVOJMSA-N 0.000 claims 1
201000006845 reticulosarcoma Diseases 0.000 claims 1
208000029922 reticulum cell sarcoma Diseases 0.000 claims 1
102200160920 rs35304565 Human genes 0.000 claims 1
CYUZWOBJPPVACB-ZCYQVOJMSA-N tert-butyl (2s)-2-[[2-[[(2s)-1-(2-aminoacetyl)pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)(C)C)C[C@@H]1CCCN1C(=O)CN CYUZWOBJPPVACB-ZCYQVOJMSA-N 0.000 claims 1
241000124008 Mammalia Species 0.000 abstract 1
238000006243 chemical reaction Methods 0.000 description 132
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
239000000243 solution Substances 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
239000000047 product Substances 0.000 description 46
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
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FORVAIDSGSLRPX-RGMNGODLSA-N methyl (2s)-2,6-diaminohexanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CCCCN FORVAIDSGSLRPX-RGMNGODLSA-N 0.000 description 1
KXWULRSLTPLVDC-ZDUSSCGKSA-N methyl (2s)-2-(isoquinoline-1-carbonylamino)-4-methylsulfanylbutanoate Chemical compound C1=CC=C2C(C(=O)N[C@@H](CCSC)C(=O)OC)=NC=CC2=C1 KXWULRSLTPLVDC-ZDUSSCGKSA-N 0.000 description 1
PNWWULIGMCXRNW-XWGVYQGASA-N methyl (2s)-2-[[2-[[(2s)-1-[(3s)-3,4-diamino-4-oxobutanoyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C=1C=CC2=CC=CC=C2C=1CN(CC(=O)N[C@@H](CCSC)C(=O)OC)C[C@@H]1CCCN1C(=O)C[C@H](N)C(N)=O PNWWULIGMCXRNW-XWGVYQGASA-N 0.000 description 1
BTTAYOKAUFIVBM-SDZVROEXSA-N methyl (2s)-2-[[2-[[(2s,3s)-3-methyl-2-[[2-[3-[(4-nitrophenyl)methyl]imidazol-4-yl]acetyl]amino]pentyl]-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound N([C@H](CN(CC(=O)N[C@@H](CCSC)C(=O)OC)CC=1C2=CC=CC=C2C=CC=1)[C@@H](C)CC)C(=O)CC1=CN=CN1CC1=CC=C([N+]([O-])=O)C=C1 BTTAYOKAUFIVBM-SDZVROEXSA-N 0.000 description 1
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KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
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229910000343 potassium bisulfate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
NUVKWLIGQHQGOJ-JTQLQIEISA-N propan-2-yl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoate Chemical compound CSCC[C@@H](C(=O)OC(C)C)NC(=O)OC(C)(C)C NUVKWLIGQHQGOJ-JTQLQIEISA-N 0.000 description 1
JLXIOVDVKLIIOJ-XCZPVHLTSA-N propan-2-yl (2s)-2-[[2-[[(2s)-1-[2-(1h-imidazol-5-yl)acetyl]pyrrolidin-2-yl]methyl-(naphthalen-1-ylmethyl)amino]acetyl]amino]-4-methylsulfanylbutanoate Chemical compound C([C@H]1CN(CC(=O)N[C@@H](CCSC)C(=O)OC(C)C)CC=2C3=CC=CC=C3C=CC=2)CCN1C(=O)CC1=CNC=N1 JLXIOVDVKLIIOJ-XCZPVHLTSA-N 0.000 description 1
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238000011002 quantification Methods 0.000 description 1
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239000012047 saturated solution Substances 0.000 description 1
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XQXNTSWARYMIBD-HNNXBMFYSA-N tert-butyl (2s)-4-(3-chlorophenyl)-2-(2-methylsulfanylethyl)-5-oxopiperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)[C@@H](CCSC)CN1C1=CC=CC(Cl)=C1 XQXNTSWARYMIBD-HNNXBMFYSA-N 0.000 description 1
VQUGQCMRKRLMOF-UHFFFAOYSA-N tert-butyl 4-(3-chlorophenyl)-3-oxopiperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC(Cl)=C1 VQUGQCMRKRLMOF-UHFFFAOYSA-N 0.000 description 1
MSKPKYQESULKCE-QHCPKHFHSA-N tert-butyl n-[(2s)-1-(2,3-dimethylanilino)-6-phenylmethoxyhexan-2-yl]carbamate Chemical compound CC1=CC=CC(NC[C@H](CCCCOCC=2C=CC=CC=2)NC(=O)OC(C)(C)C)=C1C MSKPKYQESULKCE-QHCPKHFHSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
LOIYMIARKYCTBW-UHFFFAOYSA-N trans-urocanic acid Natural products OC(=O)C=CC1=CNC=N1 LOIYMIARKYCTBW-UHFFFAOYSA-N 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
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239000003039 volatile agent Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Gastroenterology & Hepatology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Steroid Compounds (AREA)

JP9535542A 1996-04-03 1997-03-31 癌治療方法 Pending JP2000504023A (ja)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US1477396P	1996-04-03	1996-04-03
GB60/014,773		1996-06-28
GB9613599.1		1996-06-28
GBGB9613599.1A GB9613599D0 (en)	1996-06-28	1996-06-28	A method of treating cancer
PCT/US1997/005328 WO1997036587A1 (en)	1996-04-03	1997-03-31	A method of treating cancer

Publications (1)

Publication Number	Publication Date
JP2000504023A true JP2000504023A (ja)	2000-04-04

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ID=26309586

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP9535542A Pending JP2000504023A (ja)	1996-04-03	1997-03-31	癌治療方法

Country Status (5)

Country	Link
EP (1)	EP0906099A4 (de)
JP (1)	JP2000504023A (de)
AU (1)	AU727939B2 (de)
CA (1)	CA2250232A1 (de)
WO (1)	WO1997036587A1 (de)

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JP2007507540A (ja) *	2003-10-02	2007-03-29	アイアールエム・リミテッド・ライアビリティ・カンパニー	タンパク質キナーゼ阻害剤としての化合物および組成物

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US6046208A (en) *	1996-01-11	2000-04-04	Smithkline Beecham Corporation	Substituted imidazole compounds
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US7301021B2 (en)	1997-07-02	2007-11-27	Smithkline Beecham Corporation	Substituted imidazole compounds
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CA2306077A1 (en)	1997-10-08	1999-04-15	Smithkline Beecham Corporation	Novel cycloalkenyl substituted compounds
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US6858617B2 (en)	1998-05-26	2005-02-22	Smithkline Beecham Corporation	Substituted imidazole compounds
GB9812523D0 (en) *	1998-06-10	1998-08-05	Angeletti P Ist Richerche Bio	Peptide inhibitors of hepatitis c virus ns3 protease
FR2780892B1 (fr) *	1998-07-08	2001-08-17	Sod Conseils Rech Applic	Utilisation d'inhibiteurs de prenyltransferases pour preparer un medicament destine a traiter les pathologies qui resultent de la fixation membranaire de la proteine g heterotrimerique
AU6256499A (en) *	1998-09-24	2000-04-10	Merck & Co., Inc.	A method of treating cancer
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AU1529901A (en)	1999-11-22	2001-06-04	Smithkline Beecham Plc	Compounds
EP1233950B1 (de)	1999-11-23	2005-10-05	Smithkline Beecham Corporation	3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p39-kinase-inhibitoren
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1997
- 1997-03-31 CA CA002250232A patent/CA2250232A1/en not_active Abandoned
- 1997-03-31 JP JP9535542A patent/JP2000504023A/ja active Pending
- 1997-03-31 EP EP97921085A patent/EP0906099A4/de not_active Withdrawn
- 1997-03-31 WO PCT/US1997/005328 patent/WO1997036587A1/en not_active Ceased
- 1997-03-31 AU AU27221/97A patent/AU727939B2/en not_active Ceased

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JP2007507540A (ja) *	2003-10-02	2007-03-29	アイアールエム・リミテッド・ライアビリティ・カンパニー	タンパク質キナーゼ阻害剤としての化合物および組成物

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Publication number	Publication date
EP0906099A4 (de)	2001-02-07
AU727939B2 (en)	2001-01-04
EP0906099A1 (de)	1999-04-07
AU2722197A (en)	1997-10-22
WO1997036587A1 (en)	1997-10-09
CA2250232A1 (en)	1997-10-09

Publication	Publication Date	Title
JP2000504023A (ja)	2000-04-04	癌治療方法
US5872135A (en)	1999-02-16	Inhibitors of farnesyl-protein transferase
US5869682A (en)	1999-02-09	Inhibitors of farnesyl-protein transferase
CA2251955A1 (en)	1997-10-23	A method of treating cancer
AU3215197A (en)	1998-01-05	A method of treating cancer
AU5322396A (en)	1996-10-16	Inhibitors of farnesyl-protein transferase
JP2000500502A (ja)	2000-01-18	ファルネシル―タンパク質トランスフェラーゼ阻害剤
CA2250190A1 (en)	1997-10-09	Inhibitors of farnesyl-protein transferase
CA2250353A1 (en)	1997-10-09	Inhibitors of farnesyl-protein transferase
AU714072B2 (en)	1999-12-16	Combinations of inhibitors of farnesyl-protein transferase
US5624936A (en)	1997-04-29	Inhibitors of farnesyl-protein transferase
EP0891349A1 (de)	1999-01-20	Inhibitoren von farnesylprotein-transferase
JPH10508006A (ja)	1998-08-04	ファルネシル−タンパク質トランスフェラーゼ阻害剤
AU717298B2 (en)	2000-03-23	Inhibitors of farnesyl-protein transferase
AU700175B2 (en)	1998-12-24	Thiol-free inhibitors of farnesyl-protein transferase
WO1996034010A2 (en)	1996-10-31	Inhibitors of farnesyl-protein transferase
US5627202A (en)	1997-05-06	Inhibitors of farnesyl-protein transferase
US5652257A (en)	1997-07-29	Heterocycle-containing inhibitors of farnesyl-protein transferase
EP0837875A2 (de)	1998-04-29	Inhibitoren der farnesyl-proteintransferase
CA2243320A1 (en)	1997-08-07	Inhibitors of farnesyl-protein transferase
JPH11502822A (ja)	1999-03-09	ファルネシル−タンパク質トランスフェラーゼ阻害剤
CA2201348A1 (en)	1996-04-04	Thiol-free inhibitors of farnesyl-protein transferase

JP2000504023A - 癌治療方法 - Google Patents

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