IL130362A - History of Quinoline-8,1 Connected Converted to Nimedazoles Linked Through Nitrogen or Carbon as Inhibitors of Prenzyl Transfer, Preparation and Pharmaceutical Preparations Containing Them - Google Patents

History of Quinoline-8,1 Connected Converted to Nimedazoles Linked Through Nitrogen or Carbon as Inhibitors of Prenzyl Transfer, Preparation and Pharmaceutical Preparations Containing Them

Info

Publication number: IL130362A
Authority: IL; Israel
Prior art keywords: formula; alkyl; hydrogen; 6alkyl; halo
Prior art date: 1997-03-10

Application number

IL13036298A

Other languages

English (en)

Hebrew (he)

Other versions

IL130362A0 (en

Original Assignee

Janssen Pharmaceutica Nv

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.)

1997-03-10

Filing date

1998-03-03

Publication date

2004-02-19

1998-03-03 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2000-06-01 Publication of IL130362A0 publication Critical patent/IL130362A0/xx

2004-02-19 Publication of IL130362A publication Critical patent/IL130362A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 10
238000002360 preparation method Methods 0.000 title description 10
230000002401 inhibitory effect Effects 0.000 title description 9
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title description 6
108010007508 Farnesyltranstransferase Proteins 0.000 title description 5
102000007317 Farnesyltranstransferase Human genes 0.000 title description 5
150000002460 imidazoles Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 123
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 76
239000001257 hydrogen Substances 0.000 claims abstract description 76
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 42
-1 Ar3-oxy Chemical group 0.000 claims abstract description 32
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 31
239000002253 acid Substances 0.000 claims abstract description 26
150000003839 salts Chemical class 0.000 claims abstract description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 18
229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
229910052717 sulfur Chemical group 0.000 claims abstract description 11
125000004951 trihalomethoxy group Chemical group 0.000 claims abstract description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
239000001301 oxygen Substances 0.000 claims abstract description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
239000011593 sulfur Chemical group 0.000 claims abstract description 7
125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 7
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
125000001475 halogen functional group Chemical group 0.000 claims abstract 16
150000002431 hydrogen Chemical class 0.000 claims description 34
238000006243 chemical reaction Methods 0.000 claims description 17
239000002585 base Substances 0.000 claims description 10
229920000137 polyphosphoric acid Polymers 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 6
230000009466 transformation Effects 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
150000002576 ketones Chemical class 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
239000012458 free base Substances 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 19
125000003545 alkoxy group Chemical group 0.000 abstract 11
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 4
125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 4
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 3
125000000217 alkyl group Chemical group 0.000 abstract 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
125000004890 (C1-C6) alkylamino group Chemical group 0.000 abstract 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 abstract 1
125000003806 alkyl carbonyl amino group Chemical group 0.000 abstract 1
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 abstract 1
230000001093 anti-cancer Effects 0.000 abstract 1
239000000203 mixture Substances 0.000 description 105
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
239000000543 intermediate Substances 0.000 description 75
239000002904 solvent Substances 0.000 description 58
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
210000004027 cell Anatomy 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
125000001309 chloro group Chemical group Cl* 0.000 description 32
239000012044 organic layer Substances 0.000 description 32
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
239000003480 eluent Substances 0.000 description 28
206010028980 Neoplasm Diseases 0.000 description 27
239000002244 precipitate Substances 0.000 description 27
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
238000004440 column chromatography Methods 0.000 description 25
150000003254 radicals Chemical class 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 23
238000012360 testing method Methods 0.000 description 20
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 19
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 18
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
108010037444 diisopropylglutathione ester Proteins 0.000 description 17
125000005843 halogen group Chemical group 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
235000011114 ammonium hydroxide Nutrition 0.000 description 13
PMZDQRJGMBOQBF-UHFFFAOYSA-N 1H-quinolin-4-one Natural products C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
230000000694 effects Effects 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
VSGPVHSTVTXREH-UHFFFAOYSA-N quinolin-4-one Chemical compound C1=CC=C[C]2C(=O)C=CN=C21 VSGPVHSTVTXREH-UHFFFAOYSA-N 0.000 description 11
108700042226 ras Genes Proteins 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
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 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
108010014186 ras Proteins Proteins 0.000 description 10
102000016914 ras Proteins Human genes 0.000 description 10
102000004190 Enzymes Human genes 0.000 description 9
108090000790 Enzymes Proteins 0.000 description 9
102000004357 Transferases Human genes 0.000 description 9
108090000992 Transferases Proteins 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
108700020796 Oncogene Proteins 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
102000043276 Oncogene Human genes 0.000 description 7
239000000872 buffer Substances 0.000 description 7
238000000034 method Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 6
230000010261 cell growth Effects 0.000 description 6
DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 6
231100000590 oncogenic Toxicity 0.000 description 6
230000002246 oncogenic effect Effects 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
201000011510 cancer Diseases 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000000502 dialysis Methods 0.000 description 5
230000012010 growth Effects 0.000 description 5
230000035772 mutation Effects 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000000047 product Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000037396 body weight Effects 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
230000030944 contact inhibition Effects 0.000 description 4
239000005457 ice water Substances 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
229960004592 isopropanol Drugs 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
238000000746 purification Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
210000004881 tumor cell Anatomy 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
108010021101 Lamin Type B Proteins 0.000 description 3
101150040459 RAS gene Proteins 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
239000000654 additive Substances 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
210000000170 cell membrane Anatomy 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
229960005235 piperonyl butoxide Drugs 0.000 description 3
235000015320 potassium carbonate Nutrition 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
230000002062 proliferating effect Effects 0.000 description 3
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
230000004614 tumor growth Effects 0.000 description 3
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 2
SCNRDAIXZJFMEX-UHFFFAOYSA-N 3-(3-chlorophenyl)prop-2-enoyl chloride Chemical compound ClC(=O)C=CC1=CC=CC(Cl)=C1 SCNRDAIXZJFMEX-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
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 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
241000699660 Mus musculus Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
229910017974 NH40H Inorganic materials 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
VKCLPVFDVVKEKU-UHFFFAOYSA-N S=[P] Chemical compound S=[P] VKCLPVFDVVKEKU-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
230000001594 aberrant effect Effects 0.000 description 2
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
229910052921 ammonium sulfate Inorganic materials 0.000 description 2
235000011130 ammonium sulphate Nutrition 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
238000003556 assay Methods 0.000 description 2
GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 0.000 description 2
239000011324 bead Substances 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
229960002685 biotin Drugs 0.000 description 2
239000011616 biotin Substances 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
229940127573 compound 38 Drugs 0.000 description 2
WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000011630 iodine Substances 0.000 description 2
230000003211 malignant effect Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 2
230000018791 negative regulation of catalytic activity Effects 0.000 description 2
238000011580 nude mouse model Methods 0.000 description 2
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
230000002018 overexpression Effects 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
239000002245 particle Substances 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
239000006187 pill Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000011160 research Methods 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
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150000004756 silanes Chemical class 0.000 description 1
KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 1
239000002356 single layer Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
229960005137 succinic acid Drugs 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
208000001608 teratocarcinoma Diseases 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 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
230000001131 transforming effect Effects 0.000 description 1
230000004565 tumor cell growth Effects 0.000 description 1
231100000588 tumorigenic Toxicity 0.000 description 1
230000000381 tumorigenic effect Effects 0.000 description 1
208000010570 urinary bladder carcinoma Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Cosmetics (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

IL13036298A 1997-03-10 1998-03-03 History of Quinoline-8,1 Connected Converted to Nimedazoles Linked Through Nitrogen or Carbon as Inhibitors of Prenzyl Transfer, Preparation and Pharmaceutical Preparations Containing Them IL130362A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP97200709		1997-03-10
EP97200708		1997-03-10
PCT/EP1998/001296 WO1998040383A1 (en)	1997-03-10	1998-03-03	Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with n- or c-linked imidazoles

Publications (2)

Publication Number	Publication Date
IL130362A0 IL130362A0 (en)	2000-06-01
IL130362A true IL130362A (en)	2004-02-19

Family

ID=26146222

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL13036298A IL130362A (en)	1997-03-10	1998-03-03	History of Quinoline-8,1 Connected Converted to Nimedazoles Linked Through Nitrogen or Carbon as Inhibitors of Prenzyl Transfer, Preparation and Pharmaceutical Preparations Containing Them

Country Status (21)

Country	Link
US (2)	US6187786B1 (de)
EP (1)	EP0970079B1 (de)
JP (1)	JP4272262B2 (de)
KR (1)	KR100549096B1 (de)
CN (1)	CN1128797C (de)
AT (1)	ATE251159T1 (de)
AU (1)	AU748702B2 (de)
BR (1)	BR9808843A (de)
CA (1)	CA2283587C (de)
DE (1)	DE69818649T2 (de)
ES (1)	ES2209127T3 (de)
HU (1)	HUP0001498A3 (de)
IL (1)	IL130362A (de)
NO (1)	NO313143B1 (de)
NZ (1)	NZ336234A (de)
PL (1)	PL191564B1 (de)
RU (1)	RU2204553C2 (de)
SK (1)	SK283927B6 (de)
TR (1)	TR199902203T2 (de)
TW (1)	TW591030B (de)
WO (1)	WO1998040383A1 (de)

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1998
- 1998-03-02 TW TW087102940A patent/TW591030B/zh not_active IP Right Cessation
- 1998-03-03 AU AU70318/98A patent/AU748702B2/en not_active Expired
- 1998-03-03 EP EP98916890A patent/EP0970079B1/de not_active Expired - Lifetime
- 1998-03-03 JP JP53919398A patent/JP4272262B2/ja not_active Expired - Lifetime
- 1998-03-03 ES ES98916890T patent/ES2209127T3/es not_active Expired - Lifetime
- 1998-03-03 IL IL13036298A patent/IL130362A/en not_active IP Right Cessation
- 1998-03-03 CA CA002283587A patent/CA2283587C/en not_active Expired - Lifetime
- 1998-03-03 AT AT98916890T patent/ATE251159T1/de not_active IP Right Cessation
- 1998-03-03 DE DE69818649T patent/DE69818649T2/de not_active Expired - Lifetime
- 1998-03-03 NZ NZ336234A patent/NZ336234A/xx unknown
- 1998-03-03 RU RU99121331/04A patent/RU2204553C2/ru active
- 1998-03-03 PL PL335518A patent/PL191564B1/pl unknown
- 1998-03-03 BR BR9808843-2A patent/BR9808843A/pt not_active Application Discontinuation
- 1998-03-03 TR TR1999/02203T patent/TR199902203T2/xx unknown
- 1998-03-03 KR KR1019997005506A patent/KR100549096B1/ko not_active Expired - Fee Related
- 1998-03-03 HU HU0001498A patent/HUP0001498A3/hu unknown
- 1998-03-03 WO PCT/EP1998/001296 patent/WO1998040383A1/en not_active Ceased
- 1998-03-03 US US09/380,856 patent/US6187786B1/en not_active Expired - Lifetime
- 1998-03-03 SK SK1217-99A patent/SK283927B6/sk unknown
- 1998-03-03 CN CN98803064A patent/CN1128797C/zh not_active Expired - Lifetime
1999
- 1999-09-02 NO NO19994268A patent/NO313143B1/no unknown
2000
- 2000-11-29 US US09/725,391 patent/US6444812B1/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
TW591030B (en)	2004-06-11
DE69818649D1 (de)	2003-11-06
ATE251159T1 (de)	2003-10-15
AU748702B2 (en)	2002-06-13
CA2283587C (en)	2007-05-01
DE69818649T2 (de)	2004-07-01
ES2209127T3 (es)	2004-06-16
NZ336234A (en)	2000-10-27
RU2204553C2 (ru)	2003-05-20
CA2283587A1 (en)	1998-09-17
PL191564B1 (pl)	2006-06-30
EP0970079A1 (de)	2000-01-12
EP0970079B1 (de)	2003-10-01
KR20000069559A (ko)	2000-11-25
US6444812B1 (en)	2002-09-03
NO313143B1 (no)	2002-08-19
IL130362A0 (en)	2000-06-01
SK121799A3 (en)	2000-05-16
WO1998040383A1 (en)	1998-09-17
US6187786B1 (en)	2001-02-13
JP4272262B2 (ja)	2009-06-03
BR9808843A (pt)	2000-07-04
US20020049327A1 (en)	2002-04-25
KR100549096B1 (ko)	2006-02-06
TR199902203T2 (xx)	1999-12-21
CN1128797C (zh)	2003-11-26
NO994268D0 (no)	1999-09-02
CN1249753A (zh)	2000-04-05
HUP0001498A2 (hu)	2000-11-28
HK1024689A1 (en)	2000-10-20
NO994268L (no)	1999-11-08
JP2001515487A (ja)	2001-09-18
SK283927B6 (sk)	2004-05-04
AU7031898A (en)	1998-09-29
PL335518A1 (en)	2000-04-25
HUP0001498A3 (en)	2001-01-29

Legal Events

Date	Code	Title
2004-07-25	FF	Patent granted
2008-04-13	KB	Patent renewed
2012-03-29	KB	Patent renewed
2016-02-29	KB	Patent renewed
2018-10-31	EXP	Patent expired

Publication	Publication Date	Title
US6187786B1 (en)	2001-02-13	Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles
US6458800B1 (en)	2002-10-01	1,2-annelated quinoline derivatives
AP1108A (en)	2002-10-02	Farnesyl protein transferase inhibiting (imidazol-5-Y1) Methyl-2-Quinoline derivatives.
PL190944B1 (pl)	2006-02-28	Pochodna chinazolinonu i sposób jej wytwarzania oraz kompozycja farmaceutyczna i sposób jej wytwarzania
EP1322644A1 (de)	2003-07-02	6-heterocyclylmethyl chinolon derivate und deren verwendung als farnesyl transferase inhibitoren
HK1024689B (en)	2004-03-05	Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with n- or c-linked imidazoles
CZ316799A3 (cs)	2000-03-15	1,8-Anelované chinolinonové deriváty substituované N- nebo C-vázanými imidazoly inhibující farnesyl transferázu
HK1012188B (en)	2002-07-26	Farnesyl protein transferase inhibiting (imidazol-5-yl) methyl-2-quinolinone derivatives
MXPA98002067A (en)	1998-11-12	Derivatives of the 2-quinolone inhibitors of the farnesil transfer
MXPA99009763A (en)	2000-09-04	Farnesyltransferase inhibiting quinazolinones