ZA200206912B - Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and preparation thereof. - Google Patents
Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and preparation thereof. Download PDFInfo
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- ZA200206912B ZA200206912B ZA200206912A ZA200206912A ZA200206912B ZA 200206912 B ZA200206912 B ZA 200206912B ZA 200206912 A ZA200206912 A ZA 200206912A ZA 200206912 A ZA200206912 A ZA 200206912A ZA 200206912 B ZA200206912 B ZA 200206912B
- Authority
- ZA
- South Africa
- Prior art keywords
- alk
- alkyl
- radical
- chlorophenyl
- radicals
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001539 azetidines Chemical class 0.000 title 2
- -1 -CO-alk Chemical group 0.000 claims description 202
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 119
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 97
- 150000003254 radicals Chemical class 0.000 claims description 93
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 81
- 125000005843 halogen group Chemical group 0.000 claims description 80
- 229910052757 nitrogen Inorganic materials 0.000 claims description 80
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 72
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 71
- 125000003545 alkoxy group Chemical group 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 58
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 57
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 51
- 229910052786 argon Inorganic materials 0.000 claims description 50
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 46
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 44
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 44
- 229910052760 oxygen Inorganic materials 0.000 claims description 44
- 239000001301 oxygen Substances 0.000 claims description 44
- 229910052717 sulfur Inorganic materials 0.000 claims description 44
- 239000011593 sulfur Substances 0.000 claims description 44
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 39
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 28
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 23
- 125000004043 oxo group Chemical group O=* 0.000 claims description 20
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 18
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 18
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 18
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 18
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 16
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 16
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 16
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 16
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000000335 thiazolyl group Chemical group 0.000 claims description 15
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 150000007522 mineralic acids Chemical class 0.000 claims description 10
- 230000003287 optical effect Effects 0.000 claims description 10
- 150000007524 organic acids Chemical class 0.000 claims description 10
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 9
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 9
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 9
- 229930192474 thiophene Natural products 0.000 claims description 9
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 6
- 125000004686 alkyl sulfanyl alkyl group Chemical group 0.000 claims description 6
- 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 claims description 6
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 5
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 10
- 150000002390 heteroarenes Chemical class 0.000 claims 5
- 229920000728 polyester Chemical group 0.000 claims 5
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 1
- UGGBYJSPWKGTIZ-UHFFFAOYSA-N C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)N1CC(N(CC=2C=NC=CC=2)S(=O)=O)C1 Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)N1CC(N(CC=2C=NC=CC=2)S(=O)=O)C1 UGGBYJSPWKGTIZ-UHFFFAOYSA-N 0.000 claims 1
- UHXKSFQELBLXHI-NRFANRHFSA-N FC1=CC(F)=CC(CN(C2CN(C2)[C@@H](C=2C=CC(Cl)=CC=2)C=2C=NC=NC=2)S(=O)=O)=C1 Chemical compound FC1=CC(F)=CC(CN(C2CN(C2)[C@@H](C=2C=CC(Cl)=CC=2)C=2C=NC=NC=2)S(=O)=O)=C1 UHXKSFQELBLXHI-NRFANRHFSA-N 0.000 claims 1
- 125000004212 difluorophenyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 80
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- 238000000034 method Methods 0.000 description 68
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
- 239000000243 solution Substances 0.000 description 63
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000002245 particle Substances 0.000 description 35
- 239000007787 solid Substances 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 33
- 235000019341 magnesium sulphate Nutrition 0.000 description 33
- 238000003756 stirring Methods 0.000 description 32
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 30
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 29
- 239000012074 organic phase Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 22
- 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 22
- 239000012429 reaction media Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 18
- 239000012442 inert solvent Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000006260 foam Substances 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 11
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 125000005270 trialkylamine group Chemical group 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- URQORJRWDYDXFF-UHFFFAOYSA-N 1-[bis(4-chlorophenyl)methyl]azetidin-3-one Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)N1CC(=O)C1 URQORJRWDYDXFF-UHFFFAOYSA-N 0.000 description 3
- IEYPLPQQZFREGI-UHFFFAOYSA-N 3-[bromo-(4-chlorophenyl)methyl]pyridine Chemical compound C1=CC(Cl)=CC=C1C(Br)C1=CC=CN=C1 IEYPLPQQZFREGI-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- YLSJHZRICOCHEL-UHFFFAOYSA-N CCC1=CC=CC(CNS(=O)=O)=N1 Chemical compound CCC1=CC=CC(CNS(=O)=O)=N1 YLSJHZRICOCHEL-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- USIVBZYEQWGVKT-UHFFFAOYSA-N FC1=CC(F)=CC(CNS(=O)=O)=C1 Chemical compound FC1=CC(F)=CC(CNS(=O)=O)=C1 USIVBZYEQWGVKT-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 3
- UMGFNRVAGXRPJN-UHFFFAOYSA-N N1=CC=CC2=CC(CNS(=O)=O)=CC=C21 Chemical compound N1=CC=CC2=CC(CNS(=O)=O)=CC=C21 UMGFNRVAGXRPJN-UHFFFAOYSA-N 0.000 description 3
- YCDYQLVYHOMDMZ-UHFFFAOYSA-N O=S(=O)NCC1=CC=CN=C1 Chemical compound O=S(=O)NCC1=CC=CN=C1 YCDYQLVYHOMDMZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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FR0002776A FR2805817B1 (fr) | 2000-03-03 | 2000-03-03 | Compositions pharmaceutiques contenant des derives d'azetidine, les nouveaux derives d'azetidine et leur preparation |
Publications (1)
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ZA200206912B true ZA200206912B (en) | 2003-11-03 |
Family
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ZA200206912A ZA200206912B (en) | 2000-03-03 | 2002-08-28 | Pharmaceutical compositions containing azetidine derivatives, novel azetidine derivatives and preparation thereof. |
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EP (1) | EP1263722B1 (uk) |
JP (1) | JP4883867B2 (uk) |
KR (1) | KR100819572B1 (uk) |
CN (1) | CN100386314C (uk) |
AT (1) | ATE478841T1 (uk) |
AU (1) | AU780880B2 (uk) |
BG (1) | BG66001B1 (uk) |
BR (1) | BR0108893B1 (uk) |
CA (1) | CA2400141C (uk) |
CY (1) | CY1111071T1 (uk) |
CZ (1) | CZ301254B6 (uk) |
DE (1) | DE60142891D1 (uk) |
DK (1) | DK1263722T3 (uk) |
DZ (1) | DZ3312A1 (uk) |
EA (1) | EA007109B1 (uk) |
EE (1) | EE05103B1 (uk) |
ES (1) | ES2351276T3 (uk) |
FR (1) | FR2805817B1 (uk) |
HR (1) | HRP20020712B1 (uk) |
HU (1) | HUP0400636A3 (uk) |
IL (2) | IL151321A0 (uk) |
MA (1) | MA26880A1 (uk) |
ME (1) | MEP9509A (uk) |
MX (1) | MXPA02008349A (uk) |
NO (1) | NO324524B1 (uk) |
NZ (1) | NZ521077A (uk) |
OA (1) | OA12222A (uk) |
PL (1) | PL208021B1 (uk) |
PT (1) | PT1263722E (uk) |
SI (1) | SI1263722T1 (uk) |
SK (1) | SK287445B6 (uk) |
TW (1) | TWI304399B (uk) |
UA (1) | UA73554C2 (uk) |
WO (1) | WO2001064634A1 (uk) |
YU (1) | YU66002A (uk) |
ZA (1) | ZA200206912B (uk) |
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ATE486842T1 (de) | 2002-03-12 | 2010-11-15 | Merck Sharp & Dohme | Substituierte amide |
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BRPI0610580B8 (pt) | 2005-05-30 | 2021-05-25 | Banyu Pharma Co Ltd | composto derivado de piperidina |
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2000
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2001
- 2001-01-03 UA UA2002097701A patent/UA73554C2/uk unknown
- 2001-02-23 TW TW090104187A patent/TWI304399B/zh not_active IP Right Cessation
- 2001-03-01 CN CNB018066437A patent/CN100386314C/zh not_active Expired - Fee Related
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- 2001-03-01 OA OA1200200270A patent/OA12222A/fr unknown
- 2001-03-01 IL IL15132101A patent/IL151321A0/xx unknown
- 2001-03-01 ES ES01909939T patent/ES2351276T3/es not_active Expired - Lifetime
- 2001-03-01 AU AU37527/01A patent/AU780880B2/en not_active Ceased
- 2001-03-01 SI SI200130981T patent/SI1263722T1/sl unknown
- 2001-03-01 CZ CZ20022923A patent/CZ301254B6/cs not_active IP Right Cessation
- 2001-03-01 DE DE60142891T patent/DE60142891D1/de not_active Expired - Lifetime
- 2001-03-01 EP EP01909939A patent/EP1263722B1/fr not_active Expired - Lifetime
- 2001-03-01 JP JP2001563477A patent/JP4883867B2/ja not_active Expired - Fee Related
- 2001-03-01 EE EEP200200485A patent/EE05103B1/xx not_active IP Right Cessation
- 2001-03-01 CA CA2400141A patent/CA2400141C/fr not_active Expired - Fee Related
- 2001-03-01 NZ NZ521077A patent/NZ521077A/en unknown
- 2001-03-01 WO PCT/FR2001/000602 patent/WO2001064634A1/fr active IP Right Grant
- 2001-03-01 SK SK1243-2002A patent/SK287445B6/sk not_active IP Right Cessation
- 2001-03-01 KR KR1020027011517A patent/KR100819572B1/ko not_active IP Right Cessation
- 2001-03-01 PL PL365046A patent/PL208021B1/pl unknown
- 2001-03-01 EA EA200200938A patent/EA007109B1/ru not_active IP Right Cessation
- 2001-03-01 DZ DZ013312A patent/DZ3312A1/fr active
- 2001-03-01 BR BRPI0108893-9A patent/BR0108893B1/pt not_active IP Right Cessation
-
2002
- 2002-08-18 IL IL151321A patent/IL151321A/en not_active IP Right Cessation
- 2002-08-28 MA MA26794A patent/MA26880A1/fr unknown
- 2002-08-28 ZA ZA200206912A patent/ZA200206912B/en unknown
- 2002-08-30 HR HRP20020712AA patent/HRP20020712B1/hr not_active IP Right Cessation
- 2002-09-02 NO NO20024177A patent/NO324524B1/no not_active IP Right Cessation
- 2002-09-03 BG BG107058A patent/BG66001B1/bg unknown
-
2010
- 2010-11-18 CY CY20101101042T patent/CY1111071T1/el unknown
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