IL130363A - Quinazolines that inhibit frenzyl transferase, their preparation and pharmaceutical preparations containing them - Google Patents

Quinazolines that inhibit frenzyl transferase, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL130363A
Authority: IL; Israel
Prior art keywords: alkyl; hydrogen; formula; 6alkyl; halo
Prior art date: 1997-04-25

Application number

IL13036398A

Other languages

English (en)

Hebrew (he)

Other versions

IL130363A0 (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.)

1997-04-25

Filing date

1998-04-17

Publication date

2002-08-14

1998-04-17 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2000-06-01 Publication of IL130363A0 publication Critical patent/IL130363A0/xx

2002-08-14 Publication of IL130363A publication Critical patent/IL130363A/en

Links

238000002360 preparation method Methods 0.000 title claims description 10
230000002401 inhibitory effect Effects 0.000 title claims description 9
239000008194 pharmaceutical composition Substances 0.000 title claims description 8
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 5
108010007508 Farnesyltranstransferase Proteins 0.000 title description 2
102000007317 Farnesyltranstransferase Human genes 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 107
239000001257 hydrogen Substances 0.000 claims abstract description 88
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 88
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 73
-1 Ar1oxy Chemical group 0.000 claims abstract description 35
239000002253 acid Substances 0.000 claims abstract description 22
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
125000001424 substituent group Chemical group 0.000 claims abstract description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
239000001301 oxygen Substances 0.000 claims abstract description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 8
125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
125000004951 trihalomethoxy group Chemical group 0.000 claims abstract description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
229910052717 sulfur Chemical group 0.000 claims abstract description 5
239000011593 sulfur Chemical group 0.000 claims abstract description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 3
125000005843 halogen group Chemical group 0.000 claims description 31
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
239000002585 base Substances 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 10
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
150000002576 ketones Chemical class 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
230000004614 tumor growth Effects 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 3
230000009466 transformation Effects 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 14
JVAQVSBUXYDHFX-UHFFFAOYSA-N 6-[amino-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinazolin-2-one Chemical compound CN1C=NC=C1C(N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=NC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 JVAQVSBUXYDHFX-UHFFFAOYSA-N 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
239000012458 free base Substances 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 abstract description 4
125000004448 alkyl carbonyl group Chemical group 0.000 abstract description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 26
125000003545 alkoxy group Chemical group 0.000 abstract 14
125000001475 halogen functional group Chemical group 0.000 abstract 8
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 5
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 4
125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 2
125000004890 (C1-C6) alkylamino 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
239000000203 mixture Substances 0.000 description 69
239000000543 intermediate Substances 0.000 description 65
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 52
239000002904 solvent Substances 0.000 description 48
210000004027 cell Anatomy 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
125000001309 chloro group Chemical group Cl* 0.000 description 20
239000012044 organic layer Substances 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
239000002244 precipitate Substances 0.000 description 18
150000003254 radicals Chemical class 0.000 description 18
239000003480 eluent Substances 0.000 description 17
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
206010028980 Neoplasm Diseases 0.000 description 15
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
108010037444 diisopropylglutathione ester Proteins 0.000 description 13
108700042226 ras Genes Proteins 0.000 description 13
108010014186 ras Proteins Proteins 0.000 description 13
102000016914 ras Proteins Human genes 0.000 description 13
239000000243 solution Substances 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
238000004440 column chromatography Methods 0.000 description 11
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 11
238000000034 method Methods 0.000 description 11
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
239000000047 product Substances 0.000 description 10
239000012279 sodium borohydride Substances 0.000 description 10
229910000033 sodium borohydride Inorganic materials 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
108090000623 proteins and genes Proteins 0.000 description 8
238000012360 testing method Methods 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
230000010261 cell growth Effects 0.000 description 7
239000005457 ice water Substances 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
230000035772 mutation Effects 0.000 description 6
231100000590 oncogenic Toxicity 0.000 description 6
230000002246 oncogenic effect Effects 0.000 description 6
229910052757 nitrogen Chemical group 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
238000000746 purification Methods 0.000 description 5
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-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
125000004432 carbon atom Chemical group C* 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
239000011521 glass Substances 0.000 description 4
230000012010 growth Effects 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
235000010446 mineral oil Nutrition 0.000 description 4
235000018102 proteins Nutrition 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
239000000725 suspension Substances 0.000 description 4
239000003826 tablet 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
239000005695 Ammonium acetate Substances 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
108700020796 Oncogene Proteins 0.000 description 3
101150040459 RAS gene Proteins 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000000654 additive Substances 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 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
239000003795 chemical substances by application Substances 0.000 description 3
230000030944 contact inhibition Effects 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
230000002140 halogenating effect Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Inorganic materials O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
XVDBWWRIXBMVJV-UHFFFAOYSA-N n-[bis(dimethylamino)phosphanyl]-n-methylmethanamine Chemical compound CN(C)P(N(C)C)N(C)C XVDBWWRIXBMVJV-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
230000002062 proliferating effect Effects 0.000 description 3
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-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
201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
238000007126 N-alkylation reaction Methods 0.000 description 2
102000043276 Oncogene Human genes 0.000 description 2
MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000007868 Raney catalyst Substances 0.000 description 2
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
229910000564 Raney nickel Inorganic materials 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
108090000992 Transferases Proteins 0.000 description 2
102000004357 Transferases Human genes 0.000 description 2
230000001594 aberrant effect Effects 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
230000033115 angiogenesis Effects 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
230000037396 body weight Effects 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
201000010099 disease Diseases 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
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 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
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
230000003211 malignant effect Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
239000002245 particle Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
CLFRUWPJQKSRRT-UHFFFAOYSA-N (4-chlorophenyl)-(4-nitrophenyl)methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=C(Cl)C=C1 CLFRUWPJQKSRRT-UHFFFAOYSA-N 0.000 description 1
CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
GTIKLPYCSAMPNG-UHFFFAOYSA-N 2-(3-chlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(CC#N)=C1 GTIKLPYCSAMPNG-UHFFFAOYSA-N 0.000 description 1
FHMVVEJYBMMVDJ-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(4-nitrophenyl)-1,3-dioxolane Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1(C=2C=CC(Cl)=CC=2)OCCO1 FHMVVEJYBMMVDJ-UHFFFAOYSA-N 0.000 description 1
YQOUWOJPPGRPPW-UHFFFAOYSA-N 2-bis(4-methylphenyl)phosphanylethyl-bis(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC(C)=CC=1)CCP(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 YQOUWOJPPGRPPW-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
125000006024 2-pentenyl group Chemical group 0.000 description 1
ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
BGEPYMMHNAKBFW-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(4-chlorophenyl)-(2-phenylimidazol-1-yl)methyl]-1h-quinazolin-2-one Chemical compound C1=CC(Cl)=CC=C1C(N1C(=NC=C1)C=1C=CC=CC=1)C1=CC=C(NC(=O)N=C2C=3C=C(Cl)C=CC=3)C2=C1 BGEPYMMHNAKBFW-UHFFFAOYSA-N 0.000 description 1
ZVCOTHAWLNIJKS-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(4-chlorophenyl)-(2-phenylimidazol-1-yl)methyl]-2-methoxyquinazoline Chemical compound C=12C=C(C(C=3C=CC(Cl)=CC=3)N3C(=NC=C3)C=3C=CC=CC=3)C=CC2=NC(OC)=NC=1C1=CC=CC(Cl)=C1 ZVCOTHAWLNIJKS-UHFFFAOYSA-N 0.000 description 1
NVCKFVKXOQUYFD-UHFFFAOYSA-N 4-(3-chlorophenyl)-6-[(4-chlorophenyl)-hydroxy-(3-methylimidazol-4-yl)methyl]-1-methylquinazolin-2-one;hydrate Chemical compound O.CN1C=NC=C1C(O)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=NC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 NVCKFVKXOQUYFD-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Medicines Containing Plant Substances (AREA)
Silver Salt Photography Or Processing Solution Therefor (AREA)
Cosmetics (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

IL13036398A 1997-04-25 1998-04-17 Quinazolines that inhibit frenzyl transferase, their preparation and pharmaceutical preparations containing them IL130363A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97201259		1997-04-25
PCT/EP1998/002357 WO1998049157A1 (en)	1997-04-25	1998-04-17	Farnesyltransferase inhibiting quinazolinones

Publications (2)

Publication Number	Publication Date
IL130363A0 IL130363A0 (en)	2000-06-01
IL130363A true IL130363A (en)	2002-08-14

Family

ID=8228267

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Application Number	Title	Priority Date	Filing Date
IL13036398A IL130363A (en)	1997-04-25	1998-04-17	Quinazolines that inhibit frenzyl transferase, their preparation and pharmaceutical preparations containing them

Country Status (22)

Country	Link
US (2)	US6177432B1 (de)
EP (1)	EP0977750B1 (de)
JP (1)	JP4308919B2 (de)
KR (1)	KR100520401B1 (de)
CN (1)	CN1094937C (de)
AT (1)	ATE366250T1 (de)
AU (1)	AU738628B2 (de)
BR (1)	BR9809398A (de)
CA (1)	CA2288140C (de)
CZ (1)	CZ296959B6 (de)
DE (1)	DE69838025T2 (de)
ES (1)	ES2289783T3 (de)
HU (1)	HUP0001122A3 (de)
IL (1)	IL130363A (de)
NO (1)	NO317576B1 (de)
NZ (1)	NZ336233A (de)
PL (1)	PL190944B1 (de)
RU (1)	RU2205831C2 (de)
SK (1)	SK146199A3 (de)
TR (1)	TR199902606T2 (de)
WO (1)	WO1998049157A1 (de)
ZA (1)	ZA983504B (de)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2205831C2 (ru) *	1997-04-25	2003-06-10	Янссен Фармацевтика Н.В.	Хиназолиноны, ингибирующие фарнезилтрансферазу
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1998
- 1998-04-17 RU RU99124815/04A patent/RU2205831C2/ru active
- 1998-04-17 HU HU0001122A patent/HUP0001122A3/hu unknown
- 1998-04-17 ES ES98924161T patent/ES2289783T3/es not_active Expired - Lifetime
- 1998-04-17 AU AU76460/98A patent/AU738628B2/en not_active Expired
- 1998-04-17 IL IL13036398A patent/IL130363A/en not_active IP Right Cessation
- 1998-04-17 CZ CZ0371799A patent/CZ296959B6/cs not_active IP Right Cessation
- 1998-04-17 CA CA002288140A patent/CA2288140C/en not_active Expired - Lifetime
- 1998-04-17 KR KR10-1999-7005507A patent/KR100520401B1/ko not_active Expired - Fee Related
- 1998-04-17 BR BR9809398-3A patent/BR9809398A/pt not_active Application Discontinuation
- 1998-04-17 DE DE69838025T patent/DE69838025T2/de not_active Expired - Lifetime
- 1998-04-17 US US09/403,705 patent/US6177432B1/en not_active Expired - Lifetime
- 1998-04-17 EP EP98924161A patent/EP0977750B1/de not_active Expired - Lifetime
- 1998-04-17 TR TR1999/02606T patent/TR199902606T2/xx unknown
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- 1998-04-17 PL PL336468A patent/PL190944B1/pl unknown
- 1998-04-17 AT AT98924161T patent/ATE366250T1/de not_active IP Right Cessation
- 1998-04-17 WO PCT/EP1998/002357 patent/WO1998049157A1/en not_active Ceased
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- 1998-04-17 CN CN98804366A patent/CN1094937C/zh not_active Expired - Lifetime
- 1998-04-24 ZA ZA9803504A patent/ZA983504B/xx unknown
1999
- 1999-10-22 NO NO19995169A patent/NO317576B1/no unknown
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TR199902606T2 (xx)	2000-07-21
ES2289783T3 (es)	2008-02-01
US6177432B1 (en)	2001-01-23
NO995169D0 (no)	1999-10-22
JP4308919B2 (ja)	2009-08-05
DE69838025D1 (de)	2007-08-16
NO317576B1 (no)	2004-11-15
PL336468A1 (en)	2000-06-19
JP2001522364A (ja)	2001-11-13
CA2288140A1 (en)	1998-11-05
EP0977750A1 (de)	2000-02-09
HUP0001122A3 (en)	2002-03-28
IL130363A0 (en)	2000-06-01
DE69838025T2 (de)	2008-05-08
CZ371799A3 (cs)	2000-02-16
CA2288140C (en)	2007-04-03
ATE366250T1 (de)	2007-07-15
RU2205831C2 (ru)	2003-06-10
HUP0001122A2 (hu)	2001-04-28
EP0977750B1 (de)	2007-07-04
NO995169L (no)	1999-12-27
CN1094937C (zh)	2002-11-27
PL190944B1 (pl)	2006-02-28
CN1252800A (zh)	2000-05-10
SK146199A3 (en)	2000-06-12
BR9809398A (pt)	2000-06-13
NZ336233A (en)	2001-01-26
AU7646098A (en)	1998-11-24
KR20000069560A (ko)	2000-11-25
CZ296959B6 (cs)	2006-08-16
US6358961B1 (en)	2002-03-19
WO1998049157A1 (en)	1998-11-05
ZA983504B (en)	1999-10-25
KR100520401B1 (ko)	2005-10-12
AU738628B2 (en)	2001-09-20

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2016-03-31	KB	Patent renewed
2018-11-29	EXP	Patent expired

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