SK6692001A3 - Certain substituted caprolactams, pharmaceutical compositions containing them and their use in treating tumors - Google Patents

Certain substituted caprolactams, pharmaceutical compositions containing them and their use in treating tumors Download PDF

Info

Publication number: SK6692001A3
Authority: SK; Slovakia
Prior art keywords: compound; formula; group; oxo; pharmaceutically acceptable
Prior art date: 1998-11-17

Application number

SK669-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Frederick Ray Kinder Jr

Kenneth Walter Bair

Christopher Turchik Jagoe

Richard William Versace

Sompong Wattanasin

Original Assignee

Novartis Ag

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.)

1998-11-17

Filing date

1999-11-15

Publication date

2001-10-08

1999-11-15 Application filed by Novartis Ag filed Critical Novartis Ag

2001-10-08 Publication of SK6692001A3 publication Critical patent/SK6692001A3/sk

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 31
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
150000001875 compounds Chemical class 0.000 claims abstract description 89
150000003839 salts Chemical class 0.000 claims abstract description 32
239000002253 acid Substances 0.000 claims abstract description 25
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
238000000034 method Methods 0.000 claims abstract description 22
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical class O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims abstract description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
125000004450 alkenylene group Chemical group 0.000 claims abstract description 8
125000002947 alkylene group Chemical group 0.000 claims abstract description 8
125000004419 alkynylene group Chemical group 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
125000003118 aryl group Chemical group 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
-1 4-n-decylphenyl Chemical group 0.000 claims description 87
239000000203 mixture Substances 0.000 claims description 34
238000002360 preparation method Methods 0.000 claims description 21
230000010933 acylation Effects 0.000 claims description 17
238000005917 acylation reaction Methods 0.000 claims description 17
239000000460 chlorine Substances 0.000 claims description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
229910052801 chlorine Inorganic materials 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 11
238000009835 boiling Methods 0.000 claims description 9
201000011510 cancer Diseases 0.000 claims description 9
239000003495 polar organic solvent Substances 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
238000002512 chemotherapy Methods 0.000 claims description 4
239000011877 solvent mixture Substances 0.000 claims description 4
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims 2
125000004434 sulfur atom Chemical group 0.000 claims 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
XSYJUVKQRPLTAU-BKMGADMVSA-N [(3r,6s)-7-oxo-6-[[(e,2r,3r,4s,5r)-3,4,5-trihydroxy-2-methoxy-8,8-dimethylnon-6-enoyl]amino]azepan-3-yl] cyclohexanecarboxylate Chemical compound C1NC(=O)[C@@H](NC(=O)[C@@H]([C@H](O)[C@@H](O)[C@H](O)\C=C\C(C)(C)C)OC)CC[C@H]1OC(=O)C1CCCCC1 XSYJUVKQRPLTAU-BKMGADMVSA-N 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
239000001301 oxygen Substances 0.000 abstract 1
239000011593 sulfur Substances 0.000 abstract 1
238000005481 NMR spectroscopy Methods 0.000 description 40
238000006243 chemical reaction Methods 0.000 description 33
210000004027 cell Anatomy 0.000 description 29
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
239000007787 solid Substances 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
230000007062 hydrolysis Effects 0.000 description 21
238000006460 hydrolysis reaction Methods 0.000 description 21
239000000047 product Substances 0.000 description 19
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
239000003960 organic solvent Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
150000001335 aliphatic alkanes Chemical class 0.000 description 10
238000012360 testing method Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
COLHPANOPVTKLZ-UHFFFAOYSA-N non-6-enamide Chemical compound CCC=CCCCCC(N)=O COLHPANOPVTKLZ-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 8
RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 8
229910000071 diazene Inorganic materials 0.000 description 8
239000000126 substance Substances 0.000 description 8
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 7
BOWUOGIPSRVRSJ-UHFFFAOYSA-N 2-aminohexano-6-lactam Chemical compound NC1CCCCNC1=O BOWUOGIPSRVRSJ-UHFFFAOYSA-N 0.000 description 6
NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
230000000259 anti-tumor effect Effects 0.000 description 6
239000002246 antineoplastic agent Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000002904 solvent Substances 0.000 description 6
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
206010006187 Breast cancer Diseases 0.000 description 5
208000026310 Breast neoplasm Diseases 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000002835 absorbance Methods 0.000 description 5
150000003973 alkyl amines Chemical class 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
150000002596 lactones Chemical class 0.000 description 5
230000014759 maintenance of location Effects 0.000 description 5
239000002609 medium Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
238000002560 therapeutic procedure Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
238000003556 assay Methods 0.000 description 4
238000006482 condensation reaction Methods 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000003586 protic polar solvent Substances 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
XOLMYDQLENZUAI-KGLIPLIRSA-N [(3r,6s)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-7-oxoazepan-3-yl] cyclohexanecarboxylate Chemical compound C1NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC[C@H]1OC(=O)C1CCCCC1 XOLMYDQLENZUAI-KGLIPLIRSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
230000037396 body weight Effects 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
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
239000012043 crude product Substances 0.000 description 3
150000001470 diamides Chemical class 0.000 description 3
229960004679 doxorubicin Drugs 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
230000012010 growth Effects 0.000 description 3
IDIOJRGTRFRIJL-UHFFFAOYSA-N iodosilane Chemical compound I[SiH3] IDIOJRGTRFRIJL-UHFFFAOYSA-N 0.000 description 3
230000011987 methylation Effects 0.000 description 3
238000007069 methylation reaction Methods 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
150000003222 pyridines Chemical class 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
SVIMTGHKHMNLAM-SFYZADRCSA-N tert-butyl n-[(3s,6r)-6-hydroxy-2-oxoazepan-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](O)CNC1=O SVIMTGHKHMNLAM-SFYZADRCSA-N 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 2
VZFUCHSFHOYXIS-UHFFFAOYSA-N Cycloheptanecarboxylic acid Chemical compound OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 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
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
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
241000288906 Primates Species 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
201000008275 breast carcinoma Diseases 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 2
229940127089 cytotoxic agent Drugs 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 2
150000004673 fluoride salts Chemical class 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000012433 hydrogen halide Substances 0.000 description 2
229910000039 hydrogen halide Inorganic materials 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical class N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
238000006772 olefination reaction Methods 0.000 description 2
239000004033 plastic Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
229910001923 silver oxide Inorganic materials 0.000 description 2
239000002356 single layer Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
238000003756 stirring Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical group CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
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YMLPRBLVLVRJDI-OLZOCXBDSA-N tert-butyl n-[(3s,6r)-6-[tert-butyl(dimethyl)silyl]oxy-2-oxoazepan-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](O[Si](C)(C)C(C)(C)C)CNC1=O YMLPRBLVLVRJDI-OLZOCXBDSA-N 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
238000010257 thawing Methods 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
208000016255 tiredness Diseases 0.000 description 1
230000003867 tiredness Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-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
239000012588 trypsin Substances 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000008673 vomiting Effects 0.000 description 1
210000003905 vulva Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
208000016261 weight loss Diseases 0.000 description 1
230000004580 weight loss Effects 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
- C07D401/12—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
- 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
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

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

SK669-2001A 1998-11-17 1999-11-15 Certain substituted caprolactams, pharmaceutical compositions containing them and their use in treating tumors SK6692001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US19335498A	1998-11-17	1998-11-17
PCT/EP1999/008767 WO2000029382A1 (en)	1998-11-17	1999-11-15	Certain substituted caprolactams, pharmaceutical compositions containing them and their use in treating tumors

Publications (1)

Publication Number	Publication Date
SK6692001A3 true SK6692001A3 (en)	2001-10-08

Family

ID=22713307

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK669-2001A SK6692001A3 (en)	1998-11-17	1999-11-15	Certain substituted caprolactams, pharmaceutical compositions containing them and their use in treating tumors

Country Status (25)

Country	Link
EP (1)	EP1131297B1 (id)
JP (1)	JP3550545B2 (id)
KR (1)	KR20010080461A (id)
CN (1)	CN1187333C (id)
AR (1)	AR023914A1 (id)
AT (1)	ATE264309T1 (id)
AU (1)	AU748016B2 (id)
BR (1)	BR9915436A (id)
CA (1)	CA2347773C (id)
CO (1)	CO5140099A1 (id)
CZ (1)	CZ20011707A3 (id)
DE (1)	DE69916488T2 (id)
ES (1)	ES2221463T3 (id)
HU (1)	HUP0104224A3 (id)
ID (1)	ID28343A (id)
IL (1)	IL142701A0 (id)
NO (1)	NO20012428L (id)
PE (1)	PE20001241A1 (id)
PL (1)	PL347633A1 (id)
PT (1)	PT1131297E (id)
SK (1)	SK6692001A3 (id)
TR (1)	TR200101366T2 (id)
UY (2)	UY25807A1 (id)
WO (1)	WO2000029382A1 (id)
ZA (1)	ZA200103419B (id)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2003532711A (ja) *	2000-05-11	2003-11-05	ノバルティスアクチエンゲゼルシャフト	置換カプロラクタム炭酸エステルおよびカプロラクタムエーテル、およびそれらの抗腫瘍薬としての使用
WO2002072555A1 (en) *	2001-03-12	2002-09-19	Novartis Ag	Process for preparing certain substituted caprolactams
CN1856486A (zh) *	2003-07-25	2006-11-01	诺瓦提斯公司	取代的内酰胺和它们作为抗癌剂的用途
US7153846B2 (en)	2003-10-24	2006-12-26	Sanofi-Aventis Deutschland Gmbh	Bengamide derivatives, process for preparing them, and their use
DE10349669B3 (de) *	2003-10-24	2005-05-25	Aventis Pharma Deutschland Gmbh	Bengamide-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung
FR2878528B1 (fr) *	2004-11-29	2008-05-16	Aventis Pharma Sa	2-alcoxy-3,4,5-trihydroxy-alkylamides, leur preparation, compositions les contenant et utilisation
FR2878525B1 (fr) *	2004-11-29	2007-02-23	Aventis Pharma Sa	Bengamides possedant un cycle caprolactame substitue, procede de preparation, compositions les contenant et utilisation
FR2901556A1 (fr)	2006-05-24	2007-11-30	Sanofi Aventis Sa	Derives de 2-alcoxy-3,4,5-trihydroxy-alkylamide, leur preparation, compositions les contenant et utilisation
FR2901554B1 (fr)	2006-05-24	2011-04-01	Sanofi Aventis	2-alcoxy-3,4,5-trihydroxy-alkylamide-benzazepine, leur preparation, compositions les contenant et utilisation
FR2901555A1 (fr)	2006-05-24	2007-11-30	Sanofi Aventis Sa	2-alcoxy-3,4,5-trihydroxy-alkylamide-benzothiazepine, leur preparation, compositions les contenant et utilisation
CN102947274A (zh)	2010-06-17	2013-02-27	诺瓦提斯公司	联苯基取代的1,3-二氢-苯并咪唑-2-亚基胺衍生物
WO2011157793A1 (en)	2010-06-17	2011-12-22	Novartis Ag	Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9411841D0 (en) *	1994-06-14	1994-08-03	Pharma Mar Sa	New antitumoral compounds from jaspis sponge

1999
- 1999-11-04 CO CO99069674A patent/CO5140099A1/es unknown
- 1999-11-15 ES ES99957309T patent/ES2221463T3/es not_active Expired - Lifetime
- 1999-11-15 AT AT99957309T patent/ATE264309T1/de not_active IP Right Cessation
- 1999-11-15 EP EP99957309A patent/EP1131297B1/en not_active Expired - Lifetime
- 1999-11-15 CN CNB998134104A patent/CN1187333C/zh not_active Expired - Fee Related
- 1999-11-15 PE PE1999001155A patent/PE20001241A1/es not_active Application Discontinuation
- 1999-11-15 BR BR9915436-6A patent/BR9915436A/pt not_active Application Discontinuation
- 1999-11-15 ID IDW00200100966A patent/ID28343A/id unknown
- 1999-11-15 HU HU0104224A patent/HUP0104224A3/hu unknown
- 1999-11-15 PT PT99957309T patent/PT1131297E/pt unknown
- 1999-11-15 SK SK669-2001A patent/SK6692001A3/sk unknown
- 1999-11-15 AU AU15060/00A patent/AU748016B2/en not_active Ceased
- 1999-11-15 DE DE69916488T patent/DE69916488T2/de not_active Expired - Lifetime
- 1999-11-15 CA CA002347773A patent/CA2347773C/en not_active Expired - Fee Related
- 1999-11-15 PL PL99347633A patent/PL347633A1/xx unknown
- 1999-11-15 IL IL14270199A patent/IL142701A0/xx unknown
- 1999-11-15 KR KR1020017006152A patent/KR20010080461A/ko not_active Ceased
- 1999-11-15 TR TR2001/01366T patent/TR200101366T2/xx unknown
- 1999-11-15 WO PCT/EP1999/008767 patent/WO2000029382A1/en not_active Ceased
- 1999-11-15 JP JP2000582369A patent/JP3550545B2/ja not_active Expired - Fee Related
- 1999-11-15 CZ CZ20011707A patent/CZ20011707A3/cs unknown
- 1999-11-15 AR ARP990105796A patent/AR023914A1/es unknown
- 1999-11-17 UY UY25807A patent/UY25807A1/es unknown
2000
- 2000-02-25 UY UY26036A patent/UY26036A1/es unknown
2001
- 2001-04-26 ZA ZA200103419A patent/ZA200103419B/en unknown
- 2001-05-16 NO NO20012428A patent/NO20012428L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CZ20011707A3 (cs)	2001-08-15
HUP0104224A3 (en)	2002-04-29
EP1131297B1 (en)	2004-04-14
PT1131297E (pt)	2004-08-31
NO20012428L (no)	2001-07-17
BR9915436A (pt)	2001-08-07
UY26036A1 (es)	2001-06-29
EP1131297A1 (en)	2001-09-12
ES2221463T3 (es)	2004-12-16
KR20010080461A (ko)	2001-08-22
TR200101366T2 (tr)	2001-10-22
JP3550545B2 (ja)	2004-08-04
PL347633A1 (en)	2002-04-22
PE20001241A1 (es)	2000-11-24
DE69916488D1 (de)	2004-05-19
AU1506000A (en)	2000-06-05
IL142701A0 (en)	2002-03-10
UY25807A1 (es)	2001-08-27
AR023914A1 (es)	2002-09-04
CN1187333C (zh)	2005-02-02
DE69916488T2 (de)	2005-03-24
HUP0104224A2 (hu)	2002-03-28
AU748016B2 (en)	2002-05-30
JP2002529536A (ja)	2002-09-10
CO5140099A1 (es)	2002-03-22
NO20012428D0 (no)	2001-05-16
ID28343A (id)	2001-05-17
ATE264309T1 (de)	2004-04-15
CA2347773C (en)	2009-03-10
CA2347773A1 (en)	2000-05-25
ZA200103419B (en)	2002-06-26
CN1326445A (zh)	2001-12-12
WO2000029382A1 (en)	2000-05-25

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AU2005308710A1 (en)	2006-06-01	2-alcoxy-3,4,5-trihydroxy-alkylamides, preparation thereof, compositions containing them and use thereof
US6555533B2 (en)	2003-04-29	Use of certain substituted caprolactams in treating tumors
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