SK33699A3 - Tricyclic compounds useful for inhibition of farnesyl protein transferase - Google Patents

Tricyclic compounds useful for inhibition of farnesyl protein transferase Download PDF

Info

Publication number: SK33699A3
Authority: SK; Slovakia
Prior art keywords: group; formula; alkyl; compound according; mixture
Prior art date: 1996-09-13

Application number

SK336-99A

Other languages

English (en)

Slovak (sk)

Inventor

Arthur G Taveras

Alan K Mallams

Adriano Afonso

Stacy W Remiszewski

F George Njoroge

Ronald J Doll

Tarik Lalwani

Carmen Alvarez

Original Assignee

Schering Corp

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

1996-09-13

Filing date

1997-09-11

Publication date

2000-03-13

1997-09-11 Application filed by Schering Corp filed Critical Schering Corp

2000-03-13 Publication of SK33699A3 publication Critical patent/SK33699A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 249
102000004357 Transferases Human genes 0.000 title claims abstract description 21
108090000992 Transferases Proteins 0.000 title claims abstract description 21
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 title claims abstract description 21
230000005764 inhibitory process Effects 0.000 title description 4
238000000034 method Methods 0.000 claims abstract description 74
210000004027 cell Anatomy 0.000 claims abstract description 20
210000004881 tumor cell Anatomy 0.000 claims abstract description 18
230000002401 inhibitory effect Effects 0.000 claims abstract description 17
-1 benzotriazol-l-yloxy, tetrazol-5-ylthio Chemical group 0.000 claims description 67
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 47
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 34
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 claims description 32
125000003118 aryl group Chemical group 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 17
229910052794 bromium Inorganic materials 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
229910052801 chlorine Inorganic materials 0.000 claims description 13
229920006395 saturated elastomer Polymers 0.000 claims description 13
229910052736 halogen Inorganic materials 0.000 claims description 12
206010028980 Neoplasm Diseases 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
125000003710 aryl alkyl group Chemical group 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 8
IXAGRXJIXIPQDR-OWOJBTEDSA-N (e)-2-nitroethenamine Chemical group N\C=C\[N+]([O-])=O IXAGRXJIXIPQDR-OWOJBTEDSA-N 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 6
201000011510 cancer Diseases 0.000 claims description 5
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
201000002528 pancreatic cancer Diseases 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
208000029742 colonic neoplasm Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000004404 heteroalkyl group Chemical group 0.000 claims description 3
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
239000012453 solvate Substances 0.000 claims description 3
206010005003 Bladder cancer Diseases 0.000 claims description 2
206010006187 Breast cancer Diseases 0.000 claims description 2
208000026310 Breast neoplasm Diseases 0.000 claims description 2
206010009944 Colon cancer Diseases 0.000 claims description 2
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
230000003325 follicular Effects 0.000 claims description 2
201000005202 lung cancer Diseases 0.000 claims description 2
208000020816 lung neoplasm Diseases 0.000 claims description 2
208000025113 myeloid leukemia Diseases 0.000 claims description 2
201000005112 urinary bladder cancer Diseases 0.000 claims description 2
239000003814 drug Substances 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
210000000066 myeloid cell Anatomy 0.000 claims 1
230000002159 abnormal effect Effects 0.000 abstract description 8
230000012010 growth Effects 0.000 abstract description 2
125000001475 halogen functional group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
239000000203 mixture Substances 0.000 description 103
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
239000000047 product Substances 0.000 description 70
239000000243 solution Substances 0.000 description 59
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 57
239000000460 chlorine Substances 0.000 description 56
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 50
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
239000000741 silica gel Substances 0.000 description 40
229910002027 silica gel Inorganic materials 0.000 description 40
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
239000007787 solid Substances 0.000 description 27
238000001819 mass spectrum Methods 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 21
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 18
239000000908 ammonium hydroxide Substances 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 16
239000000284 extract Substances 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 14
108010014186 ras Proteins Proteins 0.000 description 14
102000016914 ras Proteins Human genes 0.000 description 14
238000010992 reflux Methods 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
238000001704 evaporation Methods 0.000 description 11
230000008020 evaporation Effects 0.000 description 11
239000010410 layer Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 11
239000000126 substance Substances 0.000 description 11
238000004587 chromatography analysis Methods 0.000 description 10
239000003480 eluent Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 8
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
125000002837 carbocyclic group Chemical group 0.000 description 7
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
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 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
238000000921 elemental analysis Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
229910004373 HOAc Inorganic materials 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
238000010828 elution Methods 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
150000002463 imidates Chemical class 0.000 description 5
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
238000003556 assay Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
125000002686 geranylgeranyl 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])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
239000008187 granular material Substances 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000005842 heteroatom Chemical group 0.000 description 4
239000007788 liquid Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
238000000926 separation method Methods 0.000 description 4
238000003756 stirring Methods 0.000 description 4
NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 4
239000000725 suspension Substances 0.000 description 4
VOCBHZWNUHMROR-UHFFFAOYSA-N 1-[4-(3-bromo-8-chloro-6,11-dihydro-5h-benzo[1,2]cyclohepta[2,4-b]pyridin-11-yl)piperazin-1-yl]-2-piperidin-4-ylethanone Chemical compound C12=NC=C(Br)C=C2CCC2=CC(Cl)=CC=C2C1N(CC1)CCN1C(=O)CC1CCNCC1 VOCBHZWNUHMROR-UHFFFAOYSA-N 0.000 description 3
GRNOZCCBOFGDCL-UHFFFAOYSA-N 2,2,2-trichloroacetyl isocyanate Chemical compound ClC(Cl)(Cl)C(=O)N=C=O GRNOZCCBOFGDCL-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
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 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
229910002091 carbon monoxide Inorganic materials 0.000 description 3
230000004663 cell proliferation Effects 0.000 description 3
239000003795 chemical substances by application Substances 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
239000008120 corn starch Substances 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000003821 enantio-separation Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
235000013305 food Nutrition 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000012458 free base Substances 0.000 description 3
125000004446 heteroarylalkyl group Chemical group 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
230000003211 malignant effect Effects 0.000 description 3
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000035772 mutation Effects 0.000 description 3
UJJUEJRWNWVHCM-UHFFFAOYSA-N n-methylsulfamoyl chloride Chemical compound CNS(Cl)(=O)=O UJJUEJRWNWVHCM-UHFFFAOYSA-N 0.000 description 3
231100000590 oncogenic Toxicity 0.000 description 3
230000002246 oncogenic effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
208000008443 pancreatic carcinoma Diseases 0.000 description 3
CWHFDTWZHFRTAB-UHFFFAOYSA-N phenyl cyanate Chemical compound N#COC1=CC=CC=C1 CWHFDTWZHFRTAB-UHFFFAOYSA-N 0.000 description 3
125000003386 piperidinyl group Chemical group 0.000 description 3
108700042226 ras Genes Proteins 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 2
VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
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229920001817 Agar Polymers 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
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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
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
229940124226 Farnesyltransferase inhibitor Drugs 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
108091006027 G proteins Proteins 0.000 description 2
102000030782 GTP binding Human genes 0.000 description 2
108091000058 GTP-Binding Proteins 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
208000005016 Intestinal Neoplasms Diseases 0.000 description 2
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150000007522 mineralic acids Chemical class 0.000 description 1
JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
YQFHPXZGXNYYLD-UHFFFAOYSA-N n-methyl-1-methylsulfanyl-2-nitroethenamine Chemical compound CNC(SC)=C[N+]([O-])=O YQFHPXZGXNYYLD-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
201000004931 neurofibromatosis Diseases 0.000 description 1
RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229910003445 palladium oxide Inorganic materials 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
238000007911 parenteral administration Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
FMQZVPXFZGISQZ-UHFFFAOYSA-N phenyl 4-[2-[4-(3-bromo-8-chloro-6,11-dihydro-5h-benzo[1,2]cyclohepta[2,4-b]pyridin-11-yl)piperazin-1-yl]-2-oxoethyl]-n-sulfamoylpiperidine-1-carboximidate Chemical compound C1CC(CC(=O)N2CCN(CC2)C2C3=NC=C(Br)C=C3CCC3=CC(Cl)=CC=C32)CCN1C(=NS(=O)(=O)N)OC1=CC=CC=C1 FMQZVPXFZGISQZ-UHFFFAOYSA-N 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
201000001275 rectum cancer Diseases 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
231100000588 tumorigenic Toxicity 0.000 description 1
230000000381 tumorigenic effect Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- 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
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- 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
- C07D405/14—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 three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- 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
- C07D471/04—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines Containing Plant Substances (AREA)
Enzymes And Modification Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK336-99A 1996-09-13 1997-09-11 Tricyclic compounds useful for inhibition of farnesyl protein transferase SK33699A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US71329796A	1996-09-13	1996-09-13
US87745397A	1997-06-17	1997-06-17
PCT/US1997/019976 WO1998011091A2 (en)	1996-09-13	1997-09-11	Tricyclic compounds useful for inhibition of farnesyl protein transferase

Publications (1)

Publication Number	Publication Date
SK33699A3 true SK33699A3 (en)	2000-03-13

Family

ID=27108965

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK336-99A SK33699A3 (en)	1996-09-13	1997-09-11	Tricyclic compounds useful for inhibition of farnesyl protein transferase

Country Status (19)

Country	Link
EP (1)	EP0934303B1 (de)
JP (1)	JP2001500515A (de)
KR (1)	KR20000036110A (de)
CN (1)	CN1237164A (de)
AT (1)	ATE286044T1 (de)
AU (1)	AU5196698A (de)
BR (1)	BR9712980A (de)
CA (1)	CA2266014A1 (de)
CZ (1)	CZ84599A3 (de)
DE (1)	DE69732123T2 (de)
ES (1)	ES2234036T3 (de)
ID (1)	ID21577A (de)
IL (1)	IL128951A0 (de)
NO (1)	NO991235L (de)
NZ (1)	NZ334454A (de)
PL (1)	PL332192A1 (de)
SK (1)	SK33699A3 (de)
TR (1)	TR199901275T2 (de)
WO (1)	WO1998011091A2 (de)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6524832B1 (en)	1994-02-04	2003-02-25	Arch Development Corporation	DNA damaging agents in combination with tyrosine kinase inhibitors
ZA985205B (en) *	1997-06-17	1998-12-15	Schering Corp	Novel n-substituted urea inhibitors of arnesyl-protein transferase
US6358968B1 (en)	1997-06-17	2002-03-19	Schering Corporation	N-substituted urea inhibitors of farnesyl-protein transferase
US5939416A (en)	1997-06-17	1999-08-17	Schering Corporation	Benzo (5,6) cycloheptapyridine compounds useful as farnesyl protein transferase inhibitors
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
JP2002519376A (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
US6316462B1 (en)	1999-04-09	2001-11-13	Schering Corporation	Methods of inducing cancer cell death and tumor regression
AU2001227757A1 (en)	2000-01-12	2001-07-24	Merck And Co., Inc.	Inhibitors of prenyl-protein transferase
WO2001051127A1 (en)	2000-01-12	2001-07-19	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
WO2001051126A1 (en)	2000-01-12	2001-07-19	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
AU2001251445A1 (en)	2000-04-10	2001-10-23	Merck And Co., Inc.	Inhibitors of prenyl-protein transferase

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4826853A (en) *	1986-10-31	1989-05-02	Schering Corporation	6,11-Dihydro-11-(N-substituted-4-piperidylidene)-5H-benzo(5,6)cyclohepta(1,2-B)pyridines and compositions and methods of use
US5089496A (en) *	1986-10-31	1992-02-18	Schering Corporation	Benzo[5,6]cycloheptapyridine compounds, compositions and method of treating allergies
KR920014799A (ko) *	1991-01-18	1992-08-25	나오가따 다이도	신규벤조[5,6]시클로헵타[1,2-b]피리딘 유도체 및 이를 함유하는 항알레르기제
IL111235A (en) *	1993-10-15	2001-03-19	Schering Plough Corp	Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them
CA2174105C (en) *	1993-10-15	2002-02-12	W. Robert Bishop	Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5719148A (en) *	1993-10-15	1998-02-17	Schering Corporation	Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
IL111257A0 (en) *	1993-10-15	1994-12-29	Schering Corp	Tricyclic sulfonamide compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5700806A (en) *	1995-03-24	1997-12-23	Schering Corporation	Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
IL117798A (en) *	1995-04-07	2001-11-25	Schering Plough Corp	Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them
IL125062A (en) *	1995-12-22	2003-11-23	Schering Corp	Tricyclic amides and pharmaceutical compositions containing them for inhibition of g-protein function and for treatment of proliferative diseases

1997
- 1997-09-11 ES ES97946875T patent/ES2234036T3/es not_active Expired - Lifetime
- 1997-09-11 JP JP10514032A patent/JP2001500515A/ja not_active Ceased
- 1997-09-11 WO PCT/US1997/019976 patent/WO1998011091A2/en not_active Ceased
- 1997-09-11 TR TR1999/01275T patent/TR199901275T2/xx unknown
- 1997-09-11 NZ NZ334454A patent/NZ334454A/xx unknown
- 1997-09-11 ID IDW990085A patent/ID21577A/id unknown
- 1997-09-11 AU AU51966/98A patent/AU5196698A/en not_active Abandoned
- 1997-09-11 EP EP97946875A patent/EP0934303B1/de not_active Expired - Lifetime
- 1997-09-11 CN CN97199597A patent/CN1237164A/zh active Pending
- 1997-09-11 KR KR1019997002133A patent/KR20000036110A/ko not_active Withdrawn
- 1997-09-11 BR BR9712980-1A patent/BR9712980A/pt unknown
- 1997-09-11 SK SK336-99A patent/SK33699A3/sk unknown
- 1997-09-11 CZ CZ99845A patent/CZ84599A3/cs unknown
- 1997-09-11 DE DE69732123T patent/DE69732123T2/de not_active Expired - Lifetime
- 1997-09-11 PL PL97332192A patent/PL332192A1/xx unknown
- 1997-09-11 AT AT97946875T patent/ATE286044T1/de not_active IP Right Cessation
- 1997-09-11 CA CA002266014A patent/CA2266014A1/en not_active Abandoned
- 1997-09-11 IL IL12895197A patent/IL128951A0/xx unknown
1999
- 1999-03-12 NO NO991235A patent/NO991235L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NZ334454A (en)	2000-08-25
CN1237164A (zh)	1999-12-01
ID21577A (id)	1999-06-24
WO1998011091A2 (en)	1998-03-19
CZ84599A3 (cs)	1999-07-14
DE69732123T2 (de)	2005-12-08
DE69732123D1 (de)	2005-02-03
KR20000036110A (ko)	2000-06-26
ATE286044T1 (de)	2005-01-15
AU5196698A (en)	1998-04-02
PL332192A1 (en)	1999-08-30
JP2001500515A (ja)	2001-01-16
IL128951A0 (en)	2000-02-17
NO991235L (no)	1999-05-10
WO1998011091A3 (en)	1998-06-11
CA2266014A1 (en)	1998-03-19
EP0934303B1 (de)	2004-12-29
ES2234036T3 (es)	2005-06-16
NO991235D0 (no)	1999-03-12
BR9712980A (pt)	2000-04-18
TR199901275T2 (xx)	1999-09-21
EP0934303A2 (de)	1999-08-11

Publication	Publication Date	Title
EP0929545B1 (de)	2004-12-29	Trizyklische inhibitoren der farnesyl protein transferase
EP0989977A1 (de)	2000-04-05	Trizyklische carboxy piperidylacetamid derivate zur inhibirrung der g-protein funktion und zur behandlung proliferativer krankheiten (farnesyl protein transferase inhibitoren)
EP0927178B1 (de)	2002-02-27	Tricyclische verbindungen zur inhibierung der g-protein funktion und für die behandlung von proliferativen erkrankungen
SK33699A3 (en)	2000-03-13	Tricyclic compounds useful for inhibition of farnesyl protein transferase
CA2264513C (en)	2004-03-30	Substituted benzocycloheptapyridine derivatives useful for inhibition of farnesyl protein transferase
CA2293712C (en)	2004-01-06	Benzo(5,6)cycloheptapyridine cyclic ureas and lactams useful as farnesyl protein transferase inhibitors
EP1019400A1 (de)	2000-07-19	Benzo[5,6]cycloheptapyridin derivate anwendbar als farnesyl protein transferase inhibitoren
US5958890A (en)	1999-09-28	Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
CA2293373C (en)	2008-09-23	Benzo(5,6)cyclohepta(1,2b)pyridine derivatives useful for inhibition of farnesyl protein transferase
DE69731481T2 (de)	2005-10-27	Verbindungen als inhibitoren von farnesylprotein-transferase
HK1018267B (en)	2002-07-05	Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
MXPA99012066A (en)	2000-09-04	Benzo(5,6)cycloheptapyridine compounds useful as farnesyl protein transferase inhibitors
HK1018443B (en)	2002-04-19	Substituted benzocycloheptapyridine derivatives useful for inhibition of farnesyl protein transferase
HK1024909B (en)	2003-08-22	Benzo(5,6)cycloheptapyridine cyclic ureas and lactams useful as farnesyl protein transferase inhibitors
KR20000036112A (ko)	2000-06-26	파네실 단백질 트랜스퍼라제를 저해하는 데 유용한 치환된 벤조사이클로헵타피리딘 유도체