JP2000504014A - ファルネシル―タンパク質転移酵素の阻害剤 - Google Patents
ファルネシル―タンパク質転移酵素の阻害剤Info
- Publication number
- JP2000504014A JP2000504014A JP9527779A JP52777997A JP2000504014A JP 2000504014 A JP2000504014 A JP 2000504014A JP 9527779 A JP9527779 A JP 9527779A JP 52777997 A JP52777997 A JP 52777997A JP 2000504014 A JP2000504014 A JP 2000504014A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- hydrogen
- unsubstituted
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 238000000034 method Methods 0.000 claims abstract description 42
- 102000004357 Transferases Human genes 0.000 claims abstract description 32
- 108090000992 Transferases Proteins 0.000 claims abstract description 32
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims description 95
- 229910052739 hydrogen Inorganic materials 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims description 69
- 150000002431 hydrogen Chemical class 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- -1 hydrogen Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000005494 pyridonyl group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 201000004569 Blindness Diseases 0.000 claims description 2
- 241000724709 Hepatitis delta virus Species 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 201000004404 Neurofibroma Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- VHWJSJBTUWUEAL-UHFFFAOYSA-N propanamide;hydrochloride Chemical compound Cl.CCC(N)=O VHWJSJBTUWUEAL-UHFFFAOYSA-N 0.000 claims 2
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 230000004263 retinal angiogenesis Effects 0.000 claims 1
- 230000006126 farnesylation Effects 0.000 abstract description 7
- 108700020796 Oncogene Proteins 0.000 abstract description 4
- 102000043276 Oncogene Human genes 0.000 abstract description 4
- 230000000973 chemotherapeutic effect Effects 0.000 abstract description 4
- 102000016914 ras Proteins Human genes 0.000 description 30
- 108010014186 ras Proteins Proteins 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 238000003556 assay Methods 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 150000003573 thiols Chemical group 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 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 4
- VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- NDKSZWKLAXIOCK-UHFFFAOYSA-N n-(3-chlorophenyl)-3-[3-[(4-cyanophenyl)methyl]imidazol-4-yl]propanamide;hydrochloride Chemical compound Cl.ClC1=CC=CC(NC(=O)CCC=2N(C=NC=2)CC=2C=CC(=CC=2)C#N)=C1 NDKSZWKLAXIOCK-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102100029974 GTPase HRas Human genes 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- YFEPBWKUBQUBKL-UHFFFAOYSA-N methyl 3-(1h-imidazol-5-yl)propanoate Chemical compound COC(=O)CCC1=CN=CN1 YFEPBWKUBQUBKL-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 108700042226 ras Genes Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VWFJDQUYCIWHTN-FBXUGWQNSA-N Farnesyl diphosphate Natural products CC(C)=CCC\C(C)=C/CC\C(C)=C/COP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-FBXUGWQNSA-N 0.000 description 2
- VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 2
- 102100039788 GTPase NRas Human genes 0.000 description 2
- 108091006109 GTPases Proteins 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101150040459 RAS gene Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 2
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 2
- 125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 108091005640 farnesylated proteins Proteins 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000012742 immunoprecipitation (IP) buffer Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- ZLKNPIVTWNMMMH-UHFFFAOYSA-N 1-imidazol-1-ylsulfonylimidazole Chemical compound C1=CN=CN1S(=O)(=O)N1C=CN=C1 ZLKNPIVTWNMMMH-UHFFFAOYSA-N 0.000 description 1
- AZWFNQKHHGQCET-UHFFFAOYSA-N 2-(2-methylphenyl)acetamide Chemical compound CC1=CC=CC=C1CC(N)=O AZWFNQKHHGQCET-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- GAIWOPZOFIPSDC-UHFFFAOYSA-N 3-[3-[(4-cyanophenyl)methyl]imidazol-4-yl]propanoic acid Chemical compound OC(=O)CCC1=CN=CN1CC1=CC=C(C#N)C=C1 GAIWOPZOFIPSDC-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
- 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 108010038049 Mating Factor Proteins 0.000 description 1
- GDIHDSKOVXEJQQ-UHFFFAOYSA-N NC(O)=O.NC(O)=O.NC(O)=O.N Chemical compound NC(O)=O.NC(O)=O.NC(O)=O.N GDIHDSKOVXEJQQ-UHFFFAOYSA-N 0.000 description 1
- 208000034827 Neointima Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000006612 Transducin Human genes 0.000 description 1
- 108010087042 Transducin Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 238000006701 autoxidation reaction Methods 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound 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 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- WOKPSXJEBSRSAT-UHFFFAOYSA-N dihydrobenzothiopyranyl sulfone group Chemical group S1C(CCC2=C1C=CC=C2)S(=O)(=O)C2SC1=C(CC2)C=CC=C1 WOKPSXJEBSRSAT-UHFFFAOYSA-N 0.000 description 1
- QGFRSPMTVBPWNK-UHFFFAOYSA-N dilithium;oxygen(2-);hydrate Chemical compound [Li+].[Li+].O.[O-2] QGFRSPMTVBPWNK-UHFFFAOYSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 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 1
- 238000002143 fast-atom bombardment mass spectrum Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005053 lamin Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- SKEFKEOTNIPLCQ-LWIQTABASA-N mating hormone Chemical compound C([C@@H](C(=O)NC(CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCS(C)=O)C(=O)NC(CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CN=CN1 SKEFKEOTNIPLCQ-LWIQTABASA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 108700024543 mos Genes Proteins 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- 206010061311 nervous system neoplasm Diseases 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 238000000879 optical micrograph Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000000858 peroxisomal effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000003804 salivary gland carcinoma Diseases 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 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
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical class [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1079896P | 1996-01-30 | 1996-01-30 | |
| GB9605708.8 | 1996-03-19 | ||
| GBGB9605708.8A GB9605708D0 (en) | 1996-03-19 | 1996-03-19 | Inhibitors of farnesyl-protein transferase |
| GB60/010,798 | 1996-03-19 | ||
| PCT/US1997/001354 WO1997027852A1 (en) | 1996-01-30 | 1997-01-27 | Inhibitors of farnesyl-protein transferase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000504014A true JP2000504014A (ja) | 2000-04-04 |
Family
ID=26308955
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9527779A Pending JP2000504014A (ja) | 1996-01-30 | 1997-01-27 | ファルネシル―タンパク質転移酵素の阻害剤 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US6066738A (enFirst) |
| EP (1) | EP0944387A1 (enFirst) |
| JP (1) | JP2000504014A (enFirst) |
| AU (1) | AU703203B2 (enFirst) |
| WO (1) | WO1997027852A1 (enFirst) |
Families Citing this family (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997027752A1 (en) * | 1996-01-30 | 1997-08-07 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5972966A (en) * | 1996-12-05 | 1999-10-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| WO1999027928A1 (en) * | 1997-12-04 | 1999-06-10 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| JP2002519427A (ja) | 1998-07-02 | 2002-07-02 | メルク エンド カムパニー インコーポレーテッド | プレニル蛋白トランスフェラーゼ阻害薬 |
| AU760027B2 (en) | 1998-07-02 | 2003-05-08 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| HRP990246A2 (en) | 1998-08-07 | 2000-06-30 | Du Pont Pharm Co | Succinoylamino benzodiazepines as inhibitors of a beta protein production |
| NZ509241A (en) | 1998-08-07 | 2003-08-29 | Du Pont Pharm Co | Succinoylamino lactams as inhibitors of alpha-beta protein production |
| JP4615727B2 (ja) | 1998-12-24 | 2011-01-19 | ブリストル−マイヤーズ スクイブ ファーマ カンパニー | Ａβタンパク質生成の阻害剤としてのスクシノイルアミノベンゾジアゼピン |
| US6960576B2 (en) | 1999-09-13 | 2005-11-01 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production |
| US6503902B2 (en) | 1999-09-13 | 2003-01-07 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production |
| EP1222176A1 (en) | 1999-10-08 | 2002-07-17 | Bristol-Myers Squibb Pharma Company | AMINO LACTAM SULFONAMIDES AS INHIBITORS OF A$g(b) PROTEIN PRODUCTION |
| US6525044B2 (en) | 2000-02-17 | 2003-02-25 | Bristol-Myers Squibb Company | Succinoylamino carbocycles and heterocycles as inhibitors of a-β protein production |
| US6495540B2 (en) | 2000-03-28 | 2002-12-17 | Bristol - Myers Squibb Pharma Company | Lactams as inhibitors of A-β protein production |
| MXPA02009729A (es) | 2000-04-03 | 2003-03-27 | Bristol Myers Squibb Pharma Co | Lactamas ciclicas como inhibidores de la produccion de la proteina a-beta. |
| AU2001253090A1 (en) | 2000-04-03 | 2001-10-15 | Bristol-Myers Squibb Pharma Company | Cyclic lactams as inhibitors of abeta protein production |
| WO2001076694A1 (en) | 2000-04-10 | 2001-10-18 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US6632812B2 (en) | 2000-04-11 | 2003-10-14 | Dupont Pharmaceuticals Company | Substituted lactams as inhibitors of Aβ protein production |
| CA2379445C (en) | 2000-06-01 | 2007-08-21 | Bristol-Myers Squibb Pharma Company | Lactams substituted by cyclic succinates as inhibitors of a.beta. protein production |
| EP1357908A4 (en) | 2001-01-30 | 2009-07-15 | Merck & Co Inc | "ACYLSULFAMIDES FOR THE TREATMENT OF FATIBILITY, DIABETES AND LIPID DISORDERS" |
| US6624162B2 (en) | 2001-10-22 | 2003-09-23 | Pfizer Inc. | Imidazopyridine compounds as 5-HT4 receptor modulators |
| MXPA03000145A (es) | 2002-01-07 | 2003-07-15 | Pfizer | Compuestos de oxo u oxi-piridina como moduladores de receptores 5-ht4. |
| ATE346058T1 (de) | 2002-01-14 | 2006-12-15 | Boehringer Ingelheim Pharma | Glucocorticoid mimetika, verfahren zu ihrer herstellung, pharmazeutische formulierungen sie enthaltend und verwendungen davon |
| HRP20040887A2 (en) | 2002-03-26 | 2005-04-30 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7268152B2 (en) | 2002-03-26 | 2007-09-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| GB0211230D0 (en) | 2002-05-16 | 2002-06-26 | Medinnova Sf | Treatment of heart failure |
| US7186864B2 (en) | 2002-05-29 | 2007-03-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7074806B2 (en) | 2002-06-06 | 2006-07-11 | Boehringer Ingelheim Pharmaceuticals, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| US7425618B2 (en) | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| CA2496175A1 (en) | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted hihydroquinolines as glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| EP1539141B1 (en) | 2002-08-29 | 2010-07-14 | Boehringer Ingelheim Pharmaceuticals Inc. | 3-(sulfonamidoethyl)-indole derivatives for use as glucocorticoid mimetics in the treatment of inflammatory, allergic and proliferative diseases |
| DOP2003000703A (es) | 2002-09-20 | 2004-03-31 | Pfizer | Compuestos de imidazopiradina como agonistas del receptor 5-ht4 |
| BR0314584A (pt) | 2002-09-20 | 2005-08-09 | Pfizer | Compostos piperidinil-imidazopiridina n-substituìda como moduladores e receptores 5-ht4 |
| US7563810B2 (en) | 2002-11-06 | 2009-07-21 | Celgene Corporation | Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases |
| US8034831B2 (en) * | 2002-11-06 | 2011-10-11 | Celgene Corporation | Methods for the treatment and management of myeloproliferative diseases using 4-(amino)-2-(2,6-Dioxo(3-piperidyl)-isoindoline-1,3-dione in combination with other therapies |
| EP1583745A1 (en) | 2003-01-03 | 2005-10-12 | Boehringer Ingelheim Pharmaceuticals Inc. | 1-propanol and 1-propylamine derivatives and their use as glucocorticoid ligands |
| EP1613273B1 (en) | 2003-04-11 | 2012-06-13 | MedImmune, LLC | Recombinant il-9 antibodies and uses thereof |
| NZ544756A (en) | 2003-07-22 | 2009-09-25 | Astex Therapeutics Ltd | 3,4-Disubstituted 1H-pyrazole compounds and their use as cyclin dependent kinases (CDK) and glycogen synthase kinase-3 (GSK-3) modulators |
| EP1660186B1 (en) | 2003-08-18 | 2013-12-25 | MedImmune, LLC | Humanization of antibodies |
| US20060228350A1 (en) * | 2003-08-18 | 2006-10-12 | Medimmune, Inc. | Framework-shuffling of antibodies |
| UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
| US7932272B2 (en) | 2003-09-30 | 2011-04-26 | Eisai R&D Management Co., Ltd. | Antifungal agent containing heterocyclic compound |
| ATE366726T1 (de) | 2003-10-16 | 2007-08-15 | Boehringer Ingelheim Pharma | Stereoselektive synthese bestimmter trifluormethylsubstituierter alkohole |
| US7795272B2 (en) | 2004-03-13 | 2010-09-14 | Boehringer Ingelheim Pharmaceutical, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof |
| US7737163B2 (en) | 2004-06-15 | 2010-06-15 | Pfizer Inc. | Benzimidazolone carboxylic acid derivatives |
| BRPI0512046A (pt) | 2004-06-15 | 2008-02-06 | Pfizer | derivados de ácido benzimidazolona carboxìlico |
| EP2422811A2 (en) | 2004-10-27 | 2012-02-29 | MedImmune, LLC | Modulation of antibody specificity by tailoring the affinity to cognate antigens |
| EP1836166B1 (en) | 2004-12-27 | 2009-06-17 | Boehringer Ingelheim Pharmaceuticals Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| KR101155335B1 (ko) * | 2005-01-07 | 2012-06-11 | 엘지전자 주식회사 | 이동통신 단말기의 멀티미디어 메시지 동작방법 |
| US20080139620A1 (en) * | 2005-01-21 | 2008-06-12 | Astex Therapeutics Limited | Pyrazole Derivatives For The Inhibition Of Cdk's And Gsk's |
| AR052559A1 (es) * | 2005-01-21 | 2007-03-21 | Astex Therapeutics Ltd | Derivados de pirazol para inhibir cdk's y gsk's |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| AR054425A1 (es) * | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| AU2006207321B2 (en) * | 2005-01-21 | 2012-09-06 | Astex Therapeutics Limited | Pharmaceutical compounds |
| EP1845973B1 (en) * | 2005-01-21 | 2015-08-12 | Astex Therapeutics Limited | Pharmaceutical compounds |
| EP1845975A1 (en) * | 2005-01-21 | 2007-10-24 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors and further antitumor agents |
| US20090036607A1 (en) * | 2005-03-03 | 2009-02-05 | Mitsubishi Rayon Co., Ltd. | Polymer particle, resin composition containing same, and molded body |
| EP1869192B1 (en) | 2005-03-18 | 2016-01-20 | MedImmune, LLC | Framework-shuffling of antibodies |
| WO2006106711A1 (ja) | 2005-03-30 | 2006-10-12 | Eisai R & D Management Co., Ltd. | ピリジン誘導体を含有する抗真菌剤 |
| AU2006261920A1 (en) | 2005-06-23 | 2007-01-04 | Medimmune, Llc | Antibody formulations having optimized aggregation and fragmentation profiles |
| TWI385169B (zh) | 2005-10-31 | 2013-02-11 | Eisai R&D Man Co Ltd | 經雜環取代之吡啶衍生物及含有彼之抗真菌劑 |
| CA2651152A1 (en) * | 2006-05-05 | 2007-11-15 | Astex Therapeutics Limited | 4- (2,6-dichloro-benzoylamino) -1h-pyrazole-3-carboxylic acid (1-methanesulphonyl-piperidin-4-yl) -amide for the treatment of cancer |
| US20090142337A1 (en) * | 2006-05-08 | 2009-06-04 | Astex Therapeutics Limited | Pharmaceutical Combinations of Diazole Derivatives for Cancer Treatment |
| EP2049516A2 (en) * | 2006-07-14 | 2009-04-22 | Astex Therapeutics Limited | Pharmaceutical compounds |
| EA021255B1 (ru) | 2006-08-28 | 2015-05-29 | Киова Хакко Кирин Ко., Лимитед | Антагонистические моноклональные антитела человека, специфичные в отношении light человека |
| WO2008070507A2 (en) | 2006-12-06 | 2008-06-12 | Boehringer Ingelheim International Gmbh | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof |
| AU2008232903B9 (en) | 2007-03-30 | 2013-09-05 | Medimmune Llc | Antibodies with decreased deamidation profiles |
| MX2010004374A (es) | 2007-10-31 | 2010-04-30 | Medimmune Llc | Armazones proteinicos. |
| US8513287B2 (en) | 2007-12-27 | 2013-08-20 | Eisai R&D Management Co., Ltd. | Heterocyclic ring and phosphonoxymethyl group substituted pyridine derivatives and antifungal agent containing same |
| SI2300472T1 (sl) | 2008-06-06 | 2012-05-31 | Boehringer Ingelheim Int | Glukokortikoidni mimetiki postopki za njihovo pripravo farmacevtski sestavki in njihove uporabe |
| AR085091A1 (es) | 2011-01-26 | 2013-09-11 | Kolltan Pharmaceuticals Inc | Anticuerpos anti-kit y sus usos |
| RU2681730C2 (ru) | 2012-07-25 | 2019-03-12 | Селлдекс Терапьютикс Инк. | Антитела против kit и их применения |
| CA2887129A1 (en) | 2012-10-09 | 2014-04-17 | Igenica, Inc. | Anti-c16orf54 antibodies and methods of use thereof |
| JP6824735B2 (ja) | 2013-06-06 | 2021-02-03 | ピエール、ファーブル、メディカマン | 抗Ｃ１０ｏｒｆ５４抗体およびその使用方法 |
| US9475874B2 (en) | 2013-08-26 | 2016-10-25 | MabVax Therapeutics, Inc. | Nucleic acids encoding human antibodies to sialyl-lewisa |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| CA2950602C (en) | 2014-06-04 | 2021-07-20 | MabVax Therapeutics, Inc. | Human monoclonal antibodies to ganglioside gd2 |
| GB201415569D0 (en) | 2014-09-03 | 2014-10-15 | C4X Discovery Ltd | Therapeutic Compounds |
| CA2970352A1 (en) | 2014-12-11 | 2016-06-16 | Pierre Fabre Medicament | Anti-c10orf54 antibodies and uses thereof |
| HRP20230046T1 (hr) | 2015-03-03 | 2023-03-03 | Kymab Limited | Protutijela, upotreba i postupci |
| US11253590B2 (en) | 2015-12-02 | 2022-02-22 | Stsciences, Inc. | Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator) |
| CN114470194A (zh) | 2015-12-02 | 2022-05-13 | 斯特库伯株式会社 | 与btn1a1免疫特异性结合的抗体和分子及其治疗用途 |
| TWI728017B (zh) | 2015-12-15 | 2021-05-21 | 瑞典商阿斯特捷利康公司 | 異吲哚化合物、包含其之醫藥組成物及其用途 |
| GB201601703D0 (en) | 2016-01-29 | 2016-03-16 | C4X Discovery Ltd | Therapeutic compounds |
| US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
| WO2018222689A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
| EP3630834A1 (en) | 2017-05-31 | 2020-04-08 | STCube & Co., Inc. | Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1 |
| CN121609797A (zh) | 2017-06-06 | 2026-03-06 | 斯特库伯株式会社 | 使用结合btn1a1或btn1a1-配体的抗体和分子治疗癌症的方法 |
| JP2020524660A (ja) | 2017-06-14 | 2020-08-20 | アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ | Ｒｏｒ−ガンマモジュレーターとして有用な２，３−ジヒドロイソインドール−１−カルボキサミド |
| EP3694889A1 (en) | 2017-10-13 | 2020-08-19 | Boehringer Ingelheim International GmbH | Human antibodies to thomsen-nouvelle (tn) antigen |
| MA53160A (fr) | 2018-07-20 | 2021-05-26 | Pf Medicament | Récepteur pour vista |
| DK4069691T3 (da) | 2019-12-06 | 2024-10-28 | Vertex Pharma | Substituerede tetrahydrofuraner som modulatorer af natriumkanaler |
| MA64853B1 (fr) | 2021-06-04 | 2025-11-28 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hétéro)aryl) tétrahydrofuran carboxamides utilisés en tant que modulateurs de canaux sodiques |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1204720A (en) * | 1982-09-30 | 1986-05-20 | Hajimu Kitahara | Packing materials for chromatographic use and a method for analysis of an enantiomer mixture using the same |
| US4749713A (en) * | 1986-03-07 | 1988-06-07 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| CA1326852C (en) * | 1987-10-16 | 1994-02-08 | Yukihisa Goto | Condensed heterocyclic compounds, a process for preparing the same and a herbicidal composition thereof |
| EP0387431A1 (en) * | 1989-03-14 | 1990-09-19 | Beecham Group Plc | Imidazole derivatives, process for their preparation and their pharmaceutical use |
| US5234917A (en) * | 1989-12-29 | 1993-08-10 | Finkelstein Joseph A | Substituted 5-(alkyl)carboxamide imidazoles |
| US5141851A (en) * | 1990-04-18 | 1992-08-25 | Board Of Regents, The University Of Texas System | Isolated farnesyl protein transferase enzyme |
| US5340828A (en) * | 1991-09-30 | 1994-08-23 | Merck & Co., Inc. | Inhibitors of farnesyl protein transferase |
| US5238922A (en) * | 1991-09-30 | 1993-08-24 | Merck & Co., Inc. | Inhibitors of farnesyl protein transferase |
| US5352705A (en) * | 1992-06-26 | 1994-10-04 | Merck & Co., Inc. | Inhibitors of farnesyl protein transferase |
| US5326773A (en) * | 1992-10-29 | 1994-07-05 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5504212A (en) * | 1992-10-29 | 1996-04-02 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5468733A (en) * | 1993-09-30 | 1995-11-21 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5439918A (en) * | 1994-03-14 | 1995-08-08 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5571792A (en) * | 1994-06-30 | 1996-11-05 | Warner-Lambert Company | Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase |
| US5571835A (en) * | 1994-09-29 | 1996-11-05 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5491164A (en) * | 1994-09-29 | 1996-02-13 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5585359A (en) * | 1994-09-29 | 1996-12-17 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5578629A (en) * | 1995-03-29 | 1996-11-26 | Merck & Co., Inc. | Benzamide-containing inhibitors of farnesyl-protein transferase |
| EP0817630A4 (en) * | 1995-03-29 | 1999-01-27 | Merck & Co Inc | INHIBITORS OF FARNESYL PROTEIN TRANSFERASE |
| US5534537A (en) * | 1995-03-29 | 1996-07-09 | Merck & Co., Inc. | Prodrugs of inhibitors of farnesyl-protein transferase |
| IL126833A0 (en) * | 1996-05-22 | 1999-08-17 | Warner Lambert Co | Inhibitors of protein farnesyl transferase |
-
1997
- 1997-01-27 JP JP9527779A patent/JP2000504014A/ja active Pending
- 1997-01-27 EP EP97904037A patent/EP0944387A1/en not_active Withdrawn
- 1997-01-27 AU AU18444/97A patent/AU703203B2/en not_active Ceased
- 1997-01-27 WO PCT/US1997/001354 patent/WO1997027852A1/en not_active Ceased
- 1997-01-27 US US09/117,260 patent/US6066738A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0944387A4 (enFirst) | 1999-09-29 |
| US6066738A (en) | 2000-05-23 |
| EP0944387A1 (en) | 1999-09-29 |
| WO1997027852A1 (en) | 1997-08-07 |
| AU703203B2 (en) | 1999-03-18 |
| AU1844497A (en) | 1997-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2000504014A (ja) | ファルネシル―タンパク質転移酵素の阻害剤 | |
| US5968965A (en) | Inhibitors of farnesyl-protein transferase | |
| US6090948A (en) | Inhibitors of farnesyl-protein transferase | |
| US5780488A (en) | Inhibitors of farnesyl-protein transferase | |
| US5925651A (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507580A (ja) | ファルネシル―タンパク質トランスフェラーゼ阻害剤 | |
| US5939557A (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507592A (ja) | ファルネシル―タンパク質トランスフェラーゼ阻害剤 | |
| US5780492A (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507585A (ja) | ファルネシルタンパク質トランスフェラーゼの阻害剤 | |
| JP2000509371A (ja) | ファルネシル―タンパク質トランスフェラーゼ阻害剤 | |
| JP2000508631A (ja) | ファルネシルタンパク質トランスフェラーゼの阻害剤 | |
| JP2000507579A (ja) | ファルネシル―タンパク質トランスフェラーゼ阻害剤 | |
| WO1997036898A1 (en) | Inhibitors of farnesyl-protein transferase | |
| EP0880320A1 (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507576A (ja) | ファルネシル―タンパク質トランスフェラーゼ阻害剤 | |
| WO1997036886A1 (en) | Inhibitors of farnesyl-protein transferase | |
| AU707416B2 (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507582A (ja) | ファルネシルプロテイントランスフェラーゼの阻害剤 | |
| JP2000507581A (ja) | ファルネシル―タンパク質転移酵素の阻害剤 | |
| US6028201A (en) | Inhibitors of farnesyl-protein transferase | |
| JP2000507586A (ja) | ファルネシル―タンパク質転移酵素の阻害剤 | |
| JP2000507584A (ja) | ファルネシル―タンパク質転移酵素の阻害剤 | |
| JP2000505797A (ja) | ファルネシル―タンパク質転移酵素の阻害剤 | |
| US5981562A (en) | Inhibitors of farnesyl-protein transferase |