JP2002507192A - ファルネシルタンパク質トランスフェラーゼの新規三環式スルホンアミドインヒビター - Google Patents
ファルネシルタンパク質トランスフェラーゼの新規三環式スルホンアミドインヒビターInfo
- Publication number
- JP2002507192A JP2002507192A JP54752198A JP54752198A JP2002507192A JP 2002507192 A JP2002507192 A JP 2002507192A JP 54752198 A JP54752198 A JP 54752198A JP 54752198 A JP54752198 A JP 54752198A JP 2002507192 A JP2002507192 A JP 2002507192A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- alkyl
- heteroaryl
- hydrogen
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 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 19
- 102000004357 Transferases Human genes 0.000 title claims abstract description 17
- 108090000992 Transferases Proteins 0.000 title claims abstract description 17
- 239000003112 inhibitor Substances 0.000 title abstract description 7
- 229940124530 sulfonamide Drugs 0.000 title abstract description 5
- 150000003456 sulfonamides Chemical class 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 61
- -1 sulfonamide compounds Chemical class 0.000 claims abstract description 41
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
- 230000002159 abnormal effect Effects 0.000 claims abstract description 11
- 230000010261 cell growth Effects 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 180
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 102000016914 ras Proteins Human genes 0.000 claims description 26
- 108010014186 ras Proteins Proteins 0.000 claims description 26
- 239000007787 solid Substances 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 23
- 210000004881 tumor cell Anatomy 0.000 claims description 23
- 210000004027 cell Anatomy 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 108700020796 Oncogene Proteins 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 108700042226 ras Genes Proteins 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 230000035772 mutation Effects 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 101150040459 RAS gene Proteins 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000025113 myeloid leukemia Diseases 0.000 claims description 3
- 210000001685 thyroid gland Anatomy 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 208000012868 Overgrowth Diseases 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 230000003325 follicular Effects 0.000 claims description 2
- 210000004907 gland Anatomy 0.000 claims description 2
- 210000000066 myeloid cell Anatomy 0.000 claims description 2
- 208000023958 prostate neoplasm Diseases 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 6
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 abstract description 6
- 108090000790 Enzymes Proteins 0.000 abstract description 6
- 241000124008 Mammalia Species 0.000 abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000000203 mixture Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 239000000460 chlorine Substances 0.000 description 47
- 239000000047 product Substances 0.000 description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 239000002253 acid Substances 0.000 description 22
- 239000000284 extract Substances 0.000 description 20
- 239000012141 concentrate Substances 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000004104 aryloxy group Chemical group 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000007858 starting material Substances 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
- 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000000010 aprotic solvent Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000002837 carbocyclic group Chemical group 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 229910004373 HOAc Inorganic materials 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000003821 enantio-separation Methods 0.000 description 4
- 230000006126 farnesylation Effects 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000030944 contact inhibition Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 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 3
- 230000012010 growth Effects 0.000 description 3
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- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
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- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-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
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- VFTOHJFKIJLYKN-UHFFFAOYSA-N 7-nitro-9h-fluoren-2-ol Chemical group [O-][N+](=O)C1=CC=C2C3=CC=C(O)C=C3CC2=C1 VFTOHJFKIJLYKN-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
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- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
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- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- KXUGUWTUFUWYRS-UHFFFAOYSA-N 1-methylimidazole-4-sulfonyl chloride Chemical compound CN1C=NC(S(Cl)(=O)=O)=C1 KXUGUWTUFUWYRS-UHFFFAOYSA-N 0.000 description 1
- CXCHEKCRJQRVNG-UHFFFAOYSA-N 2,2,2-trifluoroethanesulfonyl chloride Chemical compound FC(F)(F)CS(Cl)(=O)=O CXCHEKCRJQRVNG-UHFFFAOYSA-N 0.000 description 1
- VHCSBTPOPKFYIU-UHFFFAOYSA-N 2-chloroethanesulfonyl chloride Chemical compound ClCCS(Cl)(=O)=O VHCSBTPOPKFYIU-UHFFFAOYSA-N 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 description 1
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- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
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- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
-
- 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
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87705097A | 1997-06-17 | 1997-06-17 | |
| US08/877,050 | 1997-06-17 | ||
| PCT/US1998/011508 WO1998057949A1 (en) | 1997-06-17 | 1998-06-15 | Novel tricyclic sulfonamide inhibitors of farnesyl-protein transferase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002507192A true JP2002507192A (ja) | 2002-03-05 |
| JP2002507192A5 JP2002507192A5 (xx) | 2005-12-08 |
Family
ID=25369146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP54752198A Pending JP2002507192A (ja) | 1997-06-17 | 1998-06-15 | ファルネシルタンパク質トランスフェラーゼの新規三環式スルホンアミドインヒビター |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0989980A1 (xx) |
| JP (1) | JP2002507192A (xx) |
| KR (1) | KR20010013826A (xx) |
| CN (1) | CN1267290A (xx) |
| AR (1) | AR012989A1 (xx) |
| AU (1) | AU8253698A (xx) |
| CA (1) | CA2293358C (xx) |
| CO (1) | CO4940475A1 (xx) |
| HU (1) | HUP0004627A2 (xx) |
| IL (1) | IL133393A0 (xx) |
| NZ (1) | NZ501619A (xx) |
| PE (1) | PE86199A1 (xx) |
| WO (1) | WO1998057949A1 (xx) |
| ZA (1) | ZA985218B (xx) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016508521A (ja) * | 2013-02-19 | 2016-03-22 | アイカーン スクール オブ メディスン アット マウント サイナイＩｃａｈｎ Ｓｃｈｏｏｌ ｏｆ Ｍｅｄｉｃｉｎｅ ａｔ Ｍｔ． Ｓｉｎａｉ | 抗腫瘍剤としての三環式複素環 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6689789B2 (en) | 1997-06-17 | 2004-02-10 | Schering Corporation | Compounds useful for inhibition of farnesyl protein transferase |
| US7517884B2 (en) | 1998-03-30 | 2009-04-14 | Kalypsys Inc. | Sulfonyl-substituted bicyclic compounds as modulators of PPAR |
| US7342016B2 (en) | 2000-08-30 | 2008-03-11 | Schering Corporation | Farnesyl protein transferase inhibitors as antitumor agents |
| JP2004514717A (ja) * | 2000-11-29 | 2004-05-20 | シェーリング コーポレイション | 新規ファルネシルプロテイントランスフェラーゼインヒビター |
| AR052319A1 (es) | 2004-10-29 | 2007-03-14 | Kalypsys Inc | Compuestos biciclicos sustituidos por sulfonilo en funcion de moduladores del ppar |
| BRPI0619282B8 (pt) | 2005-10-25 | 2021-05-25 | Kalypsys Inc | sal, e composição farmacêutica |
| WO2008091863A1 (en) | 2007-01-23 | 2008-07-31 | Kalypsys, Inc. | Sulfonyl-substituted bicyclic compounds as ppar modulators for the treatment of non-alcoholic steatohepatitis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08510445A (ja) * | 1993-10-15 | 1996-11-05 | シェーリング コーポレイション | Ｇ−タンパク質機能の阻害および増殖性疾患の治療に有用な三環式スルホンアミド化合物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| IL117797A0 (en) * | 1995-04-07 | 1996-08-04 | Pharmacopeia Inc | Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases |
-
1998
- 1998-06-15 CN CN98808186A patent/CN1267290A/zh active Pending
- 1998-06-15 HU HU0004627A patent/HUP0004627A2/hu unknown
- 1998-06-15 NZ NZ501619A patent/NZ501619A/en unknown
- 1998-06-15 PE PE1998000508A patent/PE86199A1/es not_active Application Discontinuation
- 1998-06-15 KR KR1019997011846A patent/KR20010013826A/ko not_active Application Discontinuation
- 1998-06-15 JP JP54752198A patent/JP2002507192A/ja active Pending
- 1998-06-15 ZA ZA985218A patent/ZA985218B/xx unknown
- 1998-06-15 CA CA002293358A patent/CA2293358C/en not_active Expired - Fee Related
- 1998-06-15 AU AU82536/98A patent/AU8253698A/en not_active Abandoned
- 1998-06-15 EP EP98932718A patent/EP0989980A1/en not_active Withdrawn
- 1998-06-15 WO PCT/US1998/011508 patent/WO1998057949A1/en not_active Application Discontinuation
- 1998-06-15 IL IL13339398A patent/IL133393A0/xx unknown
- 1998-06-16 CO CO98034142A patent/CO4940475A1/es unknown
- 1998-06-16 AR ARP980102859A patent/AR012989A1/es unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08510445A (ja) * | 1993-10-15 | 1996-11-05 | シェーリング コーポレイション | Ｇ−タンパク質機能の阻害および増殖性疾患の治療に有用な三環式スルホンアミド化合物 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016508521A (ja) * | 2013-02-19 | 2016-03-22 | アイカーン スクール オブ メディスン アット マウント サイナイＩｃａｈｎ Ｓｃｈｏｏｌ ｏｆ Ｍｅｄｉｃｉｎｅ ａｔ Ｍｔ． Ｓｉｎａｉ | 抗腫瘍剤としての三環式複素環 |
Also Published As
| Publication number | Publication date |
|---|---|
| CO4940475A1 (es) | 2000-07-24 |
| CA2293358C (en) | 2008-08-05 |
| PE86199A1 (es) | 1999-09-24 |
| EP0989980A1 (en) | 2000-04-05 |
| ZA985218B (en) | 1998-12-15 |
| AU8253698A (en) | 1999-01-04 |
| CA2293358A1 (en) | 1998-12-23 |
| IL133393A0 (en) | 2001-04-30 |
| HUP0004627A2 (hu) | 2001-10-28 |
| NZ501619A (en) | 2002-02-01 |
| CN1267290A (zh) | 2000-09-20 |
| WO1998057949A1 (en) | 1998-12-23 |
| AR012989A1 (es) | 2000-11-22 |
| KR20010013826A (ko) | 2001-02-26 |
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