SK3695A3 - Ornithine decarboxylase inhibiting cyclic aminooxy compounds - Google Patents

Ornithine decarboxylase inhibiting cyclic aminooxy compounds Download PDF

Info

Publication number: SK3695A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; salt; group; carbon atoms
Prior art date: 1993-04-13

Application number

SK36-95A

Other languages

English (en)

Slovak (sk)

Inventor

Jorg Frei

Jaroslav Stanek

Original Assignee

Ciba Geigy 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.)

1993-04-13

Filing date

1994-04-02

Publication date

1995-07-11

1994-04-02 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1995-07-11 Publication of SK3695A3 publication Critical patent/SK3695A3/sk

Links

102000052812 Ornithine decarboxylases Human genes 0.000 title claims description 35
108700005126 Ornithine decarboxylases Proteins 0.000 title claims description 35
230000002401 inhibitory effect Effects 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 233
150000003839 salts Chemical class 0.000 claims abstract description 114
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 63
125000003277 amino group Chemical group 0.000 claims abstract description 24
125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 9
-1 3-aminooxymethylcyclobutylmethylamine Chemical compound 0.000 claims description 165
239000000203 mixture Substances 0.000 claims description 84
238000006243 chemical reaction Methods 0.000 claims description 58
238000000034 method Methods 0.000 claims description 54
125000006239 protecting group Chemical group 0.000 claims description 46
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 30
238000011282 treatment Methods 0.000 claims description 30
230000005764 inhibitory process Effects 0.000 claims description 19
238000002360 preparation method Methods 0.000 claims description 18
239000008194 pharmaceutical composition Substances 0.000 claims description 17
230000008569 process Effects 0.000 claims description 17
201000010099 disease Diseases 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 11
125000005838 1,3-cyclopentylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:2])C([H])([H])C1([H])[*:1] 0.000 claims description 9
241001465754 Metazoa Species 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
206010028980 Neoplasm Diseases 0.000 claims description 5
125000000524 functional group Chemical group 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 4
206010037075 Protozoal infections Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 3
230000000069 prophylactic effect Effects 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
208000031295 Animal disease Diseases 0.000 claims 1
102000004031 Carboxy-Lyases Human genes 0.000 claims 1
108090000489 Carboxy-Lyases Proteins 0.000 claims 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 1
LKNRREDOTQDVTP-URHBZAFASA-N NOC[C@H]1C[C@H](N)C1 Chemical compound NOC[C@H]1C[C@H](N)C1 LKNRREDOTQDVTP-URHBZAFASA-N 0.000 claims 1
BYTVHKDJAGIKDO-IZLXSQMJSA-N NO[C@H]1CC[C@H](N)CC1 Chemical compound NO[C@H]1CC[C@H](N)CC1 BYTVHKDJAGIKDO-IZLXSQMJSA-N 0.000 claims 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims 1
LLIVDLOLUDCUEQ-WDSKDSINSA-N o-[(1s,3s)-3-aminocyclohexyl]hydroxylamine Chemical compound NO[C@H]1CCC[C@H](N)C1 LLIVDLOLUDCUEQ-WDSKDSINSA-N 0.000 claims 1
LKNRREDOTQDVTP-UHFFFAOYSA-N o-[(3-aminocyclobutyl)methyl]hydroxylamine Chemical compound NOCC1CC(N)C1 LKNRREDOTQDVTP-UHFFFAOYSA-N 0.000 claims 1
NLXJFIMDVKLIBC-WHFBIAKZSA-N o-[[(1r,2r)-2-(aminomethyl)cyclopropyl]methyl]hydroxylamine Chemical compound NC[C@@H]1C[C@H]1CON NLXJFIMDVKLIBC-WHFBIAKZSA-N 0.000 claims 1
229960003104 ornithine Drugs 0.000 claims 1
229910052799 carbon Inorganic materials 0.000 abstract description 20
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 6
239000002818 ornithine decarboxylase inhibitor Substances 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 103
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
235000002639 sodium chloride Nutrition 0.000 description 78
239000002253 acid Substances 0.000 description 71
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
125000002887 hydroxy group Chemical group [H]O* 0.000 description 51
239000000243 solution Substances 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 41
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
239000007858 starting material Substances 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
239000002585 base Substances 0.000 description 28
229910002027 silica gel Inorganic materials 0.000 description 28
239000000741 silica gel Substances 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 28
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 28
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 26
238000009835 boiling Methods 0.000 description 26
239000002904 solvent Substances 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
125000002252 acyl group Chemical group 0.000 description 22
125000000217 alkyl group Chemical group 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
238000003756 stirring Methods 0.000 description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
239000004480 active ingredient Substances 0.000 description 18
238000001704 evaporation Methods 0.000 description 18
229910052757 nitrogen Inorganic materials 0.000 description 17
125000004453 alkoxycarbonyl group Chemical group 0.000 description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
150000001298 alcohols Chemical class 0.000 description 15
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 14
239000003054 catalyst Substances 0.000 description 14
239000003960 organic solvent Substances 0.000 description 14
239000000047 product Substances 0.000 description 14
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 13
CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 13
238000003818 flash chromatography Methods 0.000 description 13
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 13
229920000768 polyamine Polymers 0.000 description 13
230000009467 reduction Effects 0.000 description 13
238000010992 reflux Methods 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
150000007513 acids Chemical class 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
239000000460 chlorine Substances 0.000 description 12
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 12
150000002170 ethers Chemical class 0.000 description 12
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 12
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 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 11
229910052801 chlorine Inorganic materials 0.000 description 11
238000002425 crystallisation Methods 0.000 description 11
230000008025 crystallization Effects 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
239000012071 phase Substances 0.000 description 11
235000015424 sodium Nutrition 0.000 description 11
125000004665 trialkylsilyl group Chemical group 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
229910052783 alkali metal Inorganic materials 0.000 description 10
229910052736 halogen Inorganic materials 0.000 description 10
125000005843 halogen group Chemical group 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
238000003776 cleavage reaction Methods 0.000 description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
229910052500 inorganic mineral Inorganic materials 0.000 description 9
235000010755 mineral Nutrition 0.000 description 9
239000011707 mineral Substances 0.000 description 9
230000007017 scission Effects 0.000 description 9
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
150000008044 alkali metal hydroxides Chemical class 0.000 description 8
125000003545 alkoxy group Chemical group 0.000 description 8
239000012267 brine Substances 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
150000002367 halogens Chemical class 0.000 description 8
238000005984 hydrogenation reaction Methods 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
125000001118 alkylidene group Chemical group 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
125000004093 cyano group Chemical group *C#N 0.000 description 7
238000011065 in-situ storage Methods 0.000 description 7
229910052751 metal Inorganic materials 0.000 description 7
239000002184 metal Substances 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
238000003797 solvolysis reaction Methods 0.000 description 7
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 6
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
239000007868 Raney catalyst Substances 0.000 description 6
229910000564 Raney nickel Inorganic materials 0.000 description 6
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
230000002378 acidificating effect Effects 0.000 description 6
239000003513 alkali Substances 0.000 description 6
150000001340 alkali metals Chemical class 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 6
239000003125 aqueous solvent Substances 0.000 description 6
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
239000002775 capsule Substances 0.000 description 6
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000000155 melt Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
125000001624 naphthyl group Chemical group 0.000 description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
238000000926 separation method Methods 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
239000012279 sodium borohydride Substances 0.000 description 6
229910000033 sodium borohydride Inorganic materials 0.000 description 6
UBXAKNTVXQMEAG-UHFFFAOYSA-L strontium sulfate Chemical compound [Sr+2].[O-]S([O-])(=O)=O UBXAKNTVXQMEAG-UHFFFAOYSA-L 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 5
241000700159 Rattus Species 0.000 description 5
125000001931 aliphatic group Chemical group 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
150000001540 azides Chemical class 0.000 description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
239000013078 crystal Substances 0.000 description 5
150000004292 cyclic ethers Chemical class 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
229930195733 hydrocarbon Natural products 0.000 description 5
150000002430 hydrocarbons Chemical class 0.000 description 5
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
239000011734 sodium Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
238000005406 washing Methods 0.000 description 5
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Tropical Medicine & Parasitology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Enzymes And Modification Thereof (AREA)

SK36-95A 1993-04-13 1994-04-02 Ornithine decarboxylase inhibiting cyclic aminooxy compounds SK3695A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CH112893		1993-04-13
PCT/EP1994/001035 WO1994024093A1 (fr)	1993-04-13	1994-04-02	Composes aminooxy cycliques inhibiteurs de la decarboxylase d'ornithine

Publications (1)

Publication Number	Publication Date
SK3695A3 true SK3695A3 (en)	1995-07-11

Family

ID=4203148

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK36-95A SK3695A3 (en)	1993-04-13	1994-04-02	Ornithine decarboxylase inhibiting cyclic aminooxy compounds

Country Status (18)

Country	Link
US (1)	US5516806A (fr)
EP (1)	EP0644872B1 (fr)
JP (1)	JPH07508045A (fr)
CN (1)	CN1034929C (fr)
AT (1)	ATE150448T1 (fr)
AU (1)	AU673736B2 (fr)
CA (1)	CA2135782A1 (fr)
CZ (1)	CZ7895A3 (fr)
DE (1)	DE69402142T2 (fr)
DK (1)	DK0644872T3 (fr)
ES (1)	ES2100060T3 (fr)
GR (1)	GR3023430T3 (fr)
HU (1)	HUT70522A (fr)
NZ (1)	NZ265252A (fr)
PL (1)	PL306764A1 (fr)
RU (1)	RU95110887A (fr)
SK (1)	SK3695A3 (fr)
WO (1)	WO1994024093A1 (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ265253A (en) *	1993-04-13	1996-10-28	Ciba Geigy Ag	Aminooxy amino alkane derivatives and medicaments
US6602862B1 (en) *	2000-09-19	2003-08-05	Merz Pharma Gmbh & Co., Kgaa	1-Amino-alkylcyclohexanes as trypanocidal agents
CN100357262C (zh) *	2002-05-10	2007-12-26	中国农业大学	(E)－O－(烃基)－α－氧代环十二酮肟,其制备方法和作为杀真菌剂的用途
WO2005075426A1 (fr) *	2004-02-03	2005-08-18	Glenmark Pharmaceuticals Ltd.	Nouveaux inhibiteurs de dipeptidyle peptidase iv, leur procedes de preparation et compositions en comportant
US7230002B2 (en)	2004-02-03	2007-06-12	Glenmark Pharmaceuticals Ltd.	Dipeptidyl peptidase IV inhibitors; processes for their preparation and compositions thereof
US10047066B2 (en)	2007-11-30	2018-08-14	Newlink Genetics Corporation	IDO inhibitors
US20170268066A1 (en) *	2016-03-15	2017-09-21	Chalmers Ventures Ab	Cancer biomarkers
CN109776502B (zh) *	2018-08-29	2021-06-08	湖北工业大学	一种含异吲哚二酮小分子抑制剂
CN118698279B (zh) *	2024-05-31	2025-04-22	江苏科创石化有限公司	一种位阻胺高效复合脱硫溶剂及其制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3192110A (en) *	1962-04-24	1965-06-29	Colgate Palmolive Co	Therapeutic aryl and thienyl hydroxylamines
US4390534A (en) *	1978-12-29	1983-06-28	Fujisawa Pharmaceutical Co., Ltd.	Cephem and cepham compounds
FR2520194A1 (fr) *	1982-01-28	1983-07-29	Roussel Uclaf	Application, comme facteur de croissance des vegetaux de la 4-nitrophenyl hydroxylamine
US4853467A (en) *	1987-05-19	1989-08-01	Bristol-Myers Company	Nitrogen containing derivatives of epipodophyllotoxin glucosides
EP0369944A1 (fr) *	1988-11-18	1990-05-23	Ciba-Geigy Ag	Oxadiaminobutanes substitués
DE3934208C2 (de) *	1989-10-13	1994-02-17	Kuesters Eduard Maschf	Spulenkörper für die induktive Beheizung von Walzen
EP0495750A3 (en) *	1991-01-14	1992-09-16	Ciba-Geigy Ag	Heterocyclic hydroxylamine
DE4105160A1 (de) *	1991-02-20	1992-08-27	Basf Ag	Imino-substiuierte phenylderivate, ihre herstellung und diese enthaltende fungizide
NZ265253A (en) *	1993-04-13	1996-10-28	Ciba Geigy Ag	Aminooxy amino alkane derivatives and medicaments

1994
- 1994-04-02 HU HU9403220A patent/HUT70522A/hu unknown
- 1994-04-02 RU RU95110887/04A patent/RU95110887A/ru unknown
- 1994-04-02 PL PL94306764A patent/PL306764A1/xx unknown
- 1994-04-02 SK SK36-95A patent/SK3695A3/sk unknown
- 1994-04-02 CN CN94190173A patent/CN1034929C/zh not_active Expired - Fee Related
- 1994-04-02 DE DE69402142T patent/DE69402142T2/de not_active Expired - Fee Related
- 1994-04-02 AT AT94913516T patent/ATE150448T1/de not_active IP Right Cessation
- 1994-04-02 DK DK94913516.4T patent/DK0644872T3/da active
- 1994-04-02 EP EP94913516A patent/EP0644872B1/fr not_active Expired - Lifetime
- 1994-04-02 WO PCT/EP1994/001035 patent/WO1994024093A1/fr not_active Ceased
- 1994-04-02 CZ CZ9578A patent/CZ7895A3/cs unknown
- 1994-04-02 NZ NZ265252A patent/NZ265252A/en unknown
- 1994-04-02 AU AU65645/94A patent/AU673736B2/en not_active Ceased
- 1994-04-02 ES ES94913516T patent/ES2100060T3/es not_active Expired - Lifetime
- 1994-04-02 CA CA002135782A patent/CA2135782A1/fr not_active Abandoned
- 1994-04-02 US US08/351,337 patent/US5516806A/en not_active Expired - Fee Related
- 1994-04-02 JP JP6522689A patent/JPH07508045A/ja active Pending
1997
- 1997-05-15 GR GR970401079T patent/GR3023430T3/el unknown

Also Published As

Publication number	Publication date
US5516806A (en)	1996-05-14
JPH07508045A (ja)	1995-09-07
AU6564594A (en)	1994-11-08
DK0644872T3 (da)	1997-10-06
HUT70522A (en)	1995-10-30
ES2100060T3 (es)	1997-06-01
GR3023430T3 (en)	1997-08-29
CN1034929C (zh)	1997-05-21
EP0644872A1 (fr)	1995-03-29
NZ265252A (en)	1996-09-25
DE69402142D1 (de)	1997-04-24
AU673736B2 (en)	1996-11-21
WO1994024093A1 (fr)	1994-10-27
PL306764A1 (en)	1995-04-18
RU95110887A (ru)	1996-10-27
CA2135782A1 (fr)	1994-10-27
CZ7895A3 (en)	1995-10-18
ATE150448T1 (de)	1997-04-15
DE69402142T2 (de)	1997-11-27
EP0644872B1 (fr)	1997-03-19
CN1104411A (zh)	1995-06-28

Publication	Publication Date	Title
EP0576357B1 (fr)	1997-03-05	Dérivés du pyrazole, procédé pour leur préparation et compositions pharmaceutiques les contenant
US5922763A (en)	1999-07-13	Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them
US6737421B1 (en)	2004-05-18	Cyclo-alkyl substituted benzimidazoles and their use as PARP inhibitors
RU2402526C2 (ru)	2010-10-27	Производные циклоалкиламина
CZ178092A3 (en)	1993-01-13	Amidine compounds and process for preparing thereof
JPH04295464A (ja)	1992-10-20	複素環式ヒドロキシルアミン
SK3695A3 (en)	1995-07-11	Ornithine decarboxylase inhibiting cyclic aminooxy compounds
US5180736A (en)	1993-01-19	Polycyclic amines useful as cerebrovascular agents
US5166152A (en)	1992-11-24	Tricyclic 3-oxo-propanenitrile derivatives
SK18998A3 (en)	1998-07-08	Prolylendopeptidase inhibitors, pharmaceutical compositions containing the same and a method for producing same
NO840310L (no)	1984-07-30	Pyrrolidinonderivater og fremgangsmaate til deres fremstilling.
US6251918B1 (en)	2001-06-26	Aniline derivatives as calcium channel blockers
US5071853A (en)	1991-12-10	Polycyclic amines useful as cerebrovascular agents
EP0644873B1 (fr)	1997-03-12	Derives d'alcane amino aminooxy a chaine ramifiee inhibiteurs de la decarboxylase d'ornithine
US2951849A (en)	1960-09-06	Hydrazine derivatives
US4446151A (en)	1984-05-01	Decarboxylase-inhibiting fluorinated pentane diamine derivatives
JP4852537B2 (ja)	2012-01-11	免疫抑制へテロ環化合物
JPH069558A (ja)	1994-01-18	飽和窒素複素環式化合物の誘導体
NO840311L (no)	1984-07-30	Substituerte pyrrolidinonderivater og fremgangsmaate til deres fremstilling.
CZ20012482A3 (cs)	2001-10-17	Deriváty ((aminoiminomethyl)amino)alkankarboxamidu a jejich pouľití v terapii
US6919328B1 (en)	2005-07-19	Tricyclic compounds with NOS activity
JPH0987237A (ja)	1997-03-31	芳香族誘導体
JP3930081B2 (ja)	2007-06-13	２−ウレイド−ベンズアミド誘導体
FR2676227A1 (fr)	1992-11-13	Nouveaux intermediaires pour la synthese de composes dialkylenepiperidino.