AU728477B2 - Inhibitors of protein farnesyltransferase - Google Patents

Inhibitors of protein farnesyltransferase Download PDF

Info

Publication number: AU728477B2
Authority: AU; Australia
Prior art keywords: methyl; imidazole; ethyl; phenyl; benzyl
Prior art date: 1996-05-22
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.): Ceased

Application number

AU28058/97A

Other languages

English (en)

Other versions

AU2805897A (en

Inventor

Ellen M. Dobrusin

Annette Marian Doherty

James Stanley Kaltenbronn

Daniele M. Leonard

Dennis Joseph Mcnamara

Judith Sebolt-Leopold

Kevon R. Shuler

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Warner Lambert Co LLC

Original Assignee

Warner Lambert Co LLC

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.)

1996-05-22

Filing date

1997-04-29

Publication date

2001-01-11

1997-04-29 Application filed by Warner Lambert Co LLC filed Critical Warner Lambert Co LLC

1997-12-09 Publication of AU2805897A publication Critical patent/AU2805897A/en

2001-01-11 Application granted granted Critical

2001-01-11 Publication of AU728477B2 publication Critical patent/AU728477B2/en

2017-04-29 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 title description 9
239000003112 inhibitor Substances 0.000 title description 5
-1 Cj-C6 alkyl Inorganic materials 0.000 claims description 440
150000001875 compounds Chemical class 0.000 claims description 327
238000000034 method Methods 0.000 claims description 102
206010028980 Neoplasm Diseases 0.000 claims description 59
229910052739 hydrogen Inorganic materials 0.000 claims description 58
239000001257 hydrogen Substances 0.000 claims description 58
239000000203 mixture Substances 0.000 claims description 55
208000037803 restenosis Diseases 0.000 claims description 53
201000011510 cancer Diseases 0.000 claims description 50
238000011282 treatment Methods 0.000 claims description 49
239000003814 drug Substances 0.000 claims description 47
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
150000002148 esters Chemical class 0.000 claims description 44
239000002253 acid Substances 0.000 claims description 41
238000004519 manufacturing process Methods 0.000 claims description 40
208000036142 Viral infection Diseases 0.000 claims description 36
230000009385 viral infection Effects 0.000 claims description 36
201000004681 Psoriasis Diseases 0.000 claims description 34
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
150000002431 hydrogen Chemical class 0.000 claims description 26
PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 25
229940080818 propionamide Drugs 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 24
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
150000001408 amides Chemical class 0.000 claims description 19
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 18
150000002367 halogens Chemical class 0.000 claims description 17
229940002612 prodrug Drugs 0.000 claims description 16
239000000651 prodrug Substances 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 14
230000002265 prevention Effects 0.000 claims description 11
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 10
229910017711 NHRa Inorganic materials 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 6
ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 4
125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 4
206010005003 Bladder cancer Diseases 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 4
125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 3
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 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 3
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 description 3
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 2
125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 2
125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
206010006187 Breast cancer Diseases 0.000 claims description 2
208000026310 Breast neoplasm Diseases 0.000 claims description 2
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
208000029742 colonic neoplasm Diseases 0.000 claims description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 2
201000005202 lung cancer Diseases 0.000 claims description 2
208000020816 lung neoplasm Diseases 0.000 claims description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
201000002528 pancreatic cancer Diseases 0.000 claims description 2
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
229910052702 rhenium Inorganic materials 0.000 claims description 2
201000002510 thyroid cancer Diseases 0.000 claims description 2
201000005112 urinary bladder cancer Diseases 0.000 claims description 2
230000000052 comparative effect Effects 0.000 claims 16
101000986989 Naja kaouthia Acidic phospholipase A2 CM-II Proteins 0.000 claims 1
GDNMFXNLQJTIBN-SFCXHYMASA-N benzyl n-[(2s)-1-[(1-amino-1-oxo-4-phenylbutan-2-yl)-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)C(C(=O)N)CCC1=CC=CC=C1 GDNMFXNLQJTIBN-SFCXHYMASA-N 0.000 claims 1
UQLQRUIIDDIQBK-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-(pyridin-3-ylmethyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CN=C1 UQLQRUIIDDIQBK-NDEPHWFRSA-N 0.000 claims 1
239000003643 water by type Substances 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
239000000243 solution Substances 0.000 description 85
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 73
239000006260 foam Substances 0.000 description 70
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
108010014186 ras Proteins Proteins 0.000 description 41
102000016914 ras Proteins Human genes 0.000 description 41
ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 40
125000000217 alkyl group Chemical group 0.000 description 40
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
239000012267 brine Substances 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 26
239000000047 product Substances 0.000 description 25
239000010410 layer Substances 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
229920006395 saturated elastomer Polymers 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 19
XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 18
238000003818 flash chromatography Methods 0.000 description 16
VKJXAQYPOTYDLO-UHFFFAOYSA-N 4-methylphenethylamine Chemical group CC1=CC=C(CCN)C=C1 VKJXAQYPOTYDLO-UHFFFAOYSA-N 0.000 description 15
239000007787 solid Substances 0.000 description 15
210000004027 cell Anatomy 0.000 description 14
229920001817 Agar Polymers 0.000 description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
235000010419 agar Nutrition 0.000 description 12
239000000706 filtrate Substances 0.000 description 11
108090000623 proteins and genes Proteins 0.000 description 11
239000000725 suspension Substances 0.000 description 11
229940086542 triethylamine Drugs 0.000 description 11
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
239000008272 agar Substances 0.000 description 10
239000002585 base Substances 0.000 description 10
239000007822 coupling agent Substances 0.000 description 10
229960004132 diethyl ether Drugs 0.000 description 10
235000018102 proteins Nutrition 0.000 description 10
102000004169 proteins and genes Human genes 0.000 description 10
239000002904 solvent Substances 0.000 description 10
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
230000012010 growth Effects 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000012321 sodium triacetoxyborohydride Substances 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 8
235000019441 ethanol Nutrition 0.000 description 8
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 8
150000004702 methyl esters Chemical class 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
239000000843 powder Substances 0.000 description 7
230000004614 tumor growth Effects 0.000 description 7
CGTWPKMZGWJCGE-UHFFFAOYSA-N 2-pyridin-2-ylethanamine;hydrochloride Chemical compound Cl.NCCC1=CC=CC=N1 CGTWPKMZGWJCGE-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
108010007508 Farnesyltranstransferase Proteins 0.000 description 6
102000007317 Farnesyltranstransferase Human genes 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
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 description 6
230000035772 mutation Effects 0.000 description 6
238000012545 processing Methods 0.000 description 6
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
WCOJOHPAKJFUDF-LBPRGKRZSA-N (2s)-3-(1h-imidazol-5-yl)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CN=CN1 WCOJOHPAKJFUDF-LBPRGKRZSA-N 0.000 description 5
AFQMWBUNDONXED-UHFFFAOYSA-N 2-phenylmethoxyethanamine;hydrochloride Chemical compound Cl.NCCOCC1=CC=CC=C1 AFQMWBUNDONXED-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
150000001413 amino acids Chemical group 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
210000000170 cell membrane Anatomy 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000000499 gel Substances 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
239000002609 medium Substances 0.000 description 5
230000002246 oncogenic effect Effects 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
238000006268 reductive amination reaction Methods 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 4
VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 4
WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical group COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 4
201000001320 Atherosclerosis Diseases 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 4
238000009643 clonogenic assay Methods 0.000 description 4
231100000096 clonogenic assay Toxicity 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
238000011534 incubation Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
231100000590 oncogenic Toxicity 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
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230000009467 reduction Effects 0.000 description 4
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210000001519 tissue Anatomy 0.000 description 4
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical group COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 3
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108091035707 Consensus sequence Proteins 0.000 description 3
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239000007821 HATU Substances 0.000 description 3
241000699660 Mus musculus Species 0.000 description 3
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
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RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000002002 slurry Substances 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
239000008107 starch Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
XIDMQWDTWMLYFS-UHFFFAOYSA-N tert-butyl 2-[(4-phenylmethoxyphenyl)methylamino]acetate Chemical compound C1=CC(CNCC(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC=C1 XIDMQWDTWMLYFS-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000002463 transducing effect Effects 0.000 description 1
238000001890 transfection Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000004222 uncontrolled growth Effects 0.000 description 1
208000010576 undifferentiated carcinoma Diseases 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
239000004474 valine Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1

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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biochemistry (AREA)
Communicable Diseases (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Oncology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Dermatology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Virology (AREA)
Pregnancy & Childbirth (AREA)
Gynecology & Obstetrics (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicines Containing Plant Substances (AREA)
Enzymes And Modification Thereof (AREA)

AU28058/97A 1996-05-22 1997-04-29 Inhibitors of protein farnesyltransferase Ceased AU728477B2 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US1611096P	1996-05-22	1996-05-22
US60/016110		1996-05-22
US3366296P	1996-12-17	1996-12-17
US60/033662		1996-12-17
PCT/US1997/006591 WO1997044350A1 (en)	1996-05-22	1997-04-29	Inhibitors of protein farnesyl transferase

Publications (2)

Publication Number	Publication Date
AU2805897A AU2805897A (en)	1997-12-09
AU728477B2 true AU728477B2 (en)	2001-01-11

Family

ID=26688183

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU28058/97A Ceased AU728477B2 (en)	1996-05-22	1997-04-29	Inhibitors of protein farnesyltransferase

Country Status (18)

Country	Link
EP (1)	EP0938494A1 (no)
JP (1)	JP2000511527A (no)
CN (1)	CN1219174A (no)
AU (1)	AU728477B2 (no)
BG (1)	BG102936A (no)
BR (1)	BR9709354A (no)
CA (1)	CA2253934A1 (no)
CO (1)	CO4960642A1 (no)
CZ (1)	CZ376498A3 (no)
EA (1)	EA199801031A1 (no)
EE (1)	EE9800408A (no)
GE (1)	GEP20012500B (no)
IL (1)	IL126833A0 (no)
NO (1)	NO985405L (no)
NZ (1)	NZ332712A (no)
PL (1)	PL330120A1 (no)
SK (1)	SK161098A3 (no)
WO (1)	WO1997044350A1 (no)

Families Citing this family (75)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU703203B2 (en) *	1996-01-30	1999-03-18	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
AU704087B2 (en) *	1996-01-30	1999-04-15	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
US6028201A (en) *	1996-01-30	2000-02-22	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
US5981562A (en) *	1996-01-30	1999-11-09	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
US5968965A (en) *	1996-01-30	1999-10-19	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
US6300501B1 (en)	1996-05-22	2001-10-09	Warner-Lambert Company	Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
US6737410B1 (en)	1997-04-11	2004-05-18	Warner-Lambert Company	Inhibitors of protein farnesyl transferase
WO1998046625A1 (en) *	1997-04-11	1998-10-22	Warner-Lambert Company	Dipeptide inhibitors of protein farnesyltransferase
US20030069231A1 (en)	1999-10-12	2003-04-10	Klaus Rudolf	Modified aminoacids, pharmaceuticals containing these compounds and method for their production
AU759492B2 (en) *	1998-04-27	2003-04-17	Warner-Lambert Company	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
US6316436B1 (en)	1998-12-08	2001-11-13	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
WO2000034437A2 (en)	1998-12-08	2000-06-15	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
WO2001051494A1 (en)	2000-01-12	2001-07-19	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
JP2002188646A (ja) *	2000-12-20	2002-07-05	Nsk Ltd	転がり軸受及び軸受装置
US7595312B2 (en)	2002-10-25	2009-09-29	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Selected CGRP antagonists, processes for preparing them and their use as pharmaceutical compositions
WO2005049589A2 (en) *	2003-10-14	2005-06-02	Cadila Healthcare Limited	Heterocyclic compounds for the treatment of hyperlipidemia, diabetes, obesity and similar diseases
DE102004015723A1 (de)	2004-03-29	2005-10-20	Boehringer Ingelheim Pharma	Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
US8362075B2 (en)	2005-05-17	2013-01-29	Merck Sharp & Dohme Corp.	Cyclohexyl sulphones for treatment of cancer
TW200804345A (en)	2005-08-30	2008-01-16	Novartis Ag	Substituted benzimidazoles and methods of preparation
GB0603041D0 (en)	2006-02-15	2006-03-29	Angeletti P Ist Richerche Bio	Therapeutic compounds
TW200813039A (en)	2006-04-19	2008-03-16	Novartis Ag	6-O-substituted benzoxazole and benzothiazole compounds and methods of inhibiting CSF-1R signaling
JP5489333B2 (ja)	2006-09-22	2014-05-14	メルク・シャープ・アンド・ドーム・コーポレーション	脂肪酸合成阻害剤を用いた治療の方法
US20110218176A1 (en)	2006-11-01	2011-09-08	Barbara Brooke Jennings-Spring	Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
CA2674436C (en)	2007-01-10	2012-07-17	Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A.	Amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors
AU2008221263B2 (en)	2007-03-01	2012-02-23	Novartis Ag	Pim kinase inhibitors and methods of their use
JP5378362B2 (ja)	2007-05-21	2013-12-25	ノバルティスアーゲー	Ｃｓｆ−１ｒ阻害剤、組成物および使用方法
EP2170076B1 (en)	2007-06-27	2016-05-18	Merck Sharp & Dohme Corp.	4-carboxybenzylamino derivatives as histone deacetylase inhibitors
US8691825B2 (en)	2009-04-01	2014-04-08	Merck Sharp & Dohme Corp.	Inhibitors of AKT activity
CN102480966B (zh)	2009-06-12	2015-09-16	达娜-法勃肿瘤研究所公司	融合的杂环化合物及其用途
US8859776B2 (en)	2009-10-14	2014-10-14	Merck Sharp & Dohme Corp.	Substituted piperidines that increase p53 activity and the uses thereof
EP2937345B1 (en)	2009-12-29	2018-03-21	Dana-Farber Cancer Institute, Inc.	Type ii raf kinase inhibitors
JP2013522292A (ja)	2010-03-16	2013-06-13	デイナファーバーキャンサーインスティチュート，インコーポレイテッド	インダゾール化合物およびそれらの使用
WO2011163330A1 (en)	2010-06-24	2011-12-29	Merck Sharp & Dohme Corp.	Novel heterocyclic compounds as erk inhibitors
CA2805265A1 (en)	2010-08-02	2012-02-09	Merck Sharp & Dohme Corp.	Rna interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (ctnnb1) gene expression using short interfering nucleic acid (sina)
HRP20191232T1 (hr)	2010-08-17	2019-11-01	Sirna Therapeutics Inc	Inhibicija, posredovana rna interferencijom, ekspresije gena virusa hepatitisa b (hbv) korištenjem kratkih interferirajućih nukleinskih kiselina (sina)
EP2608669B1 (en)	2010-08-23	2016-06-22	Merck Sharp & Dohme Corp.	NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
US8946216B2 (en)	2010-09-01	2015-02-03	Merck Sharp & Dohme Corp.	Indazole derivatives useful as ERK inhibitors
US9242981B2 (en)	2010-09-16	2016-01-26	Merck Sharp & Dohme Corp.	Fused pyrazole derivatives as novel ERK inhibitors
DK2632472T3 (en)	2010-10-29	2018-03-19	Sirna Therapeutics Inc	RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA)
EP2654748B1 (en)	2010-12-21	2016-07-27	Merck Sharp & Dohme Corp.	Indazole derivatives useful as erk inhibitors
AU2012245455A1 (en)	2011-04-21	2013-10-31	Merck Sharp & Dohme Corp.	Insulin-Like Growth Factor-1 Receptor inhibitors
EP2770987B1 (en)	2011-10-27	2018-04-04	Merck Sharp & Dohme Corp.	Novel compounds that are erk inhibitors
JP6106685B2 (ja)	2011-11-17	2017-04-05	ダナ−ファーバーキャンサーインスティテュート，インコーポレイテッド	Ｃ−ｊｕｎ−ｎ−末端キナーゼ（ｊｎｋ）の阻害剤
EP2844261B1 (en)	2012-05-02	2018-10-17	Sirna Therapeutics, Inc.	SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
JP6280554B2 (ja)	2012-09-28	2018-02-14	メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋＳｈａｒｐ＆ＤｏｈｍｅＣｏｒｐ．	Ｅｒｋ阻害剤である新規化合物
EP2909194A1 (en)	2012-10-18	2015-08-26	Dana-Farber Cancer Institute, Inc.	Inhibitors of cyclin-dependent kinase 7 (cdk7)
WO2014063061A1 (en)	2012-10-19	2014-04-24	Dana-Farber Cancer Institute, Inc.	Hydrophobically tagged small molecules as inducers of protein degradation
US10000483B2 (en)	2012-10-19	2018-06-19	Dana-Farber Cancer Institute, Inc.	Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
AU2013352568B2 (en)	2012-11-28	2019-09-19	Merck Sharp & Dohme Llc	Compositions and methods for treating cancer
KR102196882B1 (ko)	2012-12-20	2020-12-30	머크 샤프 앤드 돔 코포레이션	Hdm2 억제제로서의 치환된 이미다조피리딘
US9540377B2 (en)	2013-01-30	2017-01-10	Merck Sharp & Dohme Corp.	2,6,7,8 substituted purines as HDM2 inhibitors
US20160194368A1 (en)	2013-09-03	2016-07-07	Moderna Therapeutics, Inc.	Circular polynucleotides
CN105849099B (zh)	2013-10-18	2020-01-17	达纳-法伯癌症研究所股份有限公司	周期蛋白依赖性激酶7(cdk7)的多环抑制剂
ES2676734T3 (es)	2013-10-18	2018-07-24	Syros Pharmaceuticals, Inc.	Compuestos heteroatómicos útiles para el tratamiento de enfermedades proliferativas
WO2015164614A1 (en)	2014-04-23	2015-10-29	Dana-Farber Cancer Institute, Inc.	Janus kinase inhibitors and uses thereof
WO2015164604A1 (en)	2014-04-23	2015-10-29	Dana-Farber Cancer Institute, Inc.	Hydrophobically tagged janus kinase inhibitors and uses thereof
JO3589B1 (ar)	2014-08-06	2020-07-05	Novartis Ag	مثبطات كيناز البروتين c وطرق استخداماتها
AU2015371251B2 (en)	2014-12-23	2020-06-11	Dana-Farber Cancer Institute, Inc.	Inhibitors of cyclin-dependent kinase 7 (CDK7)
JP6861166B2 (ja)	2015-03-27	2021-04-21	ダナ−ファーバーキャンサーインスティテュート，インコーポレイテッド	サイクリン依存性キナーゼの阻害剤
CA2986441A1 (en)	2015-06-12	2016-12-15	Dana-Farber Cancer Institute, Inc.	Combination therapy of transcription inhibitors and kinase inhibitors
CA2996978A1 (en)	2015-09-09	2017-03-16	Dana-Farber Cancer Institute, Inc.	Inhibitors of cyclin-dependent kinases
JOP20190055A1 (ar)	2016-09-26	2019-03-24	Merck Sharp & Dohme	أجسام مضادة ضد cd27
US10975084B2 (en)	2016-10-12	2021-04-13	Merck Sharp & Dohme Corp.	KDM5 inhibitors
EP3609922A2 (en)	2017-04-13	2020-02-19	Aduro Biotech Holdings, Europe B.V.	Anti-sirp alpha antibodies
WO2019094312A1 (en)	2017-11-08	2019-05-16	Merck Sharp & Dohme Corp.	Prmt5 inhibitors
WO2019094311A1 (en)	2017-11-08	2019-05-16	Merck Sharp & Dohme Corp.	Prmt5 inhibitors
WO2019148412A1 (en)	2018-02-01	2019-08-08	Merck Sharp & Dohme Corp.	Anti-pd-1/lag3 bispecific antibodies
US12187701B2 (en)	2018-06-25	2025-01-07	Dana-Farber Cancer Institute, Inc.	Taire family kinase inhibitors and uses thereof
CN112805006B (zh)	2018-08-07	2024-09-24	默沙东有限责任公司	Prmt5抑制剂
EP3833668B1 (en)	2018-08-07	2025-03-19	Merck Sharp & Dohme LLC	Prmt5 inhibitors
EP3833667B1 (en)	2018-08-07	2024-03-13	Merck Sharp & Dohme LLC	Prmt5 inhibitors
AU2019413694B2 (en)	2018-12-28	2025-03-20	Dana-Farber Cancer Institute, Inc.	Inhibitors of cyclin-dependent kinase 7 and uses thereof
US12441730B2 (en)	2019-12-17	2025-10-14	Merck Sharp & Dohme Llc	PRMT5 inhibitors
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1996000736A1 (en) *	1994-06-30	1996-01-11	Warner-Lambert Company	Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5352705A (en) *	1992-06-26	1994-10-04	Merck & Co., Inc.	Inhibitors of farnesyl protein transferase
US5576293A (en) *	1993-09-30	1996-11-19	Merck & Co., Inc.	Inhibitors of farnesyl-protein transferase
NZ275691A (en) *	1993-11-05	1998-03-25	Warner Lambert Co	Di and tripeptides and compositions thereof which inhibit farnesyl transferase

1997
- 1997-04-29 EA EA199801031A patent/EA199801031A1/ru unknown
- 1997-04-29 EE EE9800408A patent/EE9800408A/xx unknown
- 1997-04-29 JP JP09542369A patent/JP2000511527A/ja not_active Abandoned
- 1997-04-29 NZ NZ332712A patent/NZ332712A/xx unknown
- 1997-04-29 WO PCT/US1997/006591 patent/WO1997044350A1/en not_active Ceased
- 1997-04-29 CA CA002253934A patent/CA2253934A1/en not_active Abandoned
- 1997-04-29 IL IL12683397A patent/IL126833A0/xx unknown
- 1997-04-29 GE GEAP19974612A patent/GEP20012500B/en unknown
- 1997-04-29 BR BR9709354A patent/BR9709354A/pt not_active Application Discontinuation
- 1997-04-29 CZ CZ983764A patent/CZ376498A3/cs unknown
- 1997-04-29 CN CN97194835A patent/CN1219174A/zh active Pending
- 1997-04-29 AU AU28058/97A patent/AU728477B2/en not_active Ceased
- 1997-04-29 SK SK1610-98A patent/SK161098A3/sk unknown
- 1997-04-29 EP EP97922365A patent/EP0938494A1/en not_active Withdrawn
- 1997-04-29 PL PL97330120A patent/PL330120A1/xx unknown
- 1997-05-26 CO CO97028769A patent/CO4960642A1/es unknown
1998
- 1998-11-19 BG BG102936A patent/BG102936A/bg unknown
- 1998-11-20 NO NO985405A patent/NO985405L/no not_active Application Discontinuation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1996000736A1 (en) *	1994-06-30	1996-01-11	Warner-Lambert Company	Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase

Also Published As

Publication number	Publication date
EA199801031A1 (ru)	1999-06-24
CN1219174A (zh)	1999-06-09
CO4960642A1 (es)	2000-09-25
CA2253934A1 (en)	1997-11-27
JP2000511527A (ja)	2000-09-05
SK161098A3 (en)	2000-06-12
BG102936A (bg)	1999-09-30
WO1997044350A1 (en)	1997-11-27
EE9800408A (et)	1999-06-15
PL330120A1 (en)	1999-04-26
NZ332712A (en)	2000-07-28
EP0938494A1 (en)	1999-09-01
GEP20012500B (en)	2001-07-25
BR9709354A (pt)	1999-08-10
NO985405D0 (no)	1998-11-20
IL126833A0 (en)	1999-08-17
AU2805897A (en)	1997-12-09
CZ376498A3 (cs)	1999-02-17
NO985405L (no)	1999-01-19

Publication	Publication Date	Title
AU728477B2 (en)	2001-01-11	Inhibitors of protein farnesyltransferase
US6300501B1 (en)	2001-10-09	Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
AU759492B2 (en)	2003-04-17	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
KR100662309B1 (ko)	2007-02-28	멜라노코르틴 수용체 리간드
US5190922A (en)	1993-03-02	Terminally modified tri-, tetra- and pentapeptide anaphylatoxin receptor ligands
WO1987004349A1 (en)	1987-07-30	Peptide analogs
US6265382B1 (en)	2001-07-24	Dipeptide inhibitors of protein farnesyltransferase
AU8523198A (en)	1999-04-01	Novel imidazolidine derivatives, their preparation, their use and pharmaceutical preparations comprising them
AU758891B2 (en)	2003-04-03	Combinations of protein farnesyltransferase and HMG CoA reductase inhibitors and their use to treat cancer
AU721786B2 (en)	2000-07-13	Cycloalkyl inhibitors of protein farnesyltransferase
US6737410B1 (en)	2004-05-18	Inhibitors of protein farnesyl transferase
CA2013475A1 (en)	1990-10-04	Amino acid derivatives
HUP9903221A2 (hu)	2000-02-28	A protein farneliz transzferáz enzimet gátló vegyületek
MXPA00009613A (en)	2001-07-31	Functionalized alkyl and alkenyl side chain derivatives of glycinamides as farnesyl transferase inhibitors
HU203249B (en)	1991-06-28	Process for producing amino acid derivatives and pharmaceutical compositions comprising same as active ingredient
KR20000015892A (ko)	2000-03-15	단백질 파르네실 트랜스퍼라제의 억제제
MXPA99001592A (es)	1999-09-20	Inhibidores cicloalquilo de proteina farnesiltransferasa
MXPA00011113A (en)	2001-07-31	Combinations of protein farnesyltransferase and hmg coa reductase inhibitors and their use to treat cancer

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2001-05-10	FGA	Letters patent sealed or granted (standard patent)