TW200410956A - Proline derivatives - Google Patents

Proline derivatives Download PDF

Info

Publication number: TW200410956A
Authority: TW; Taiwan
Prior art keywords: group; compound; atom; lower alkyl; nmr
Prior art date: 2002-08-23

Application number

TW092123113A

Other languages

English (en)

Chinese (zh)

Inventor

Masahiro Fujita

Masato Sakamoto

Nobuhiko Horiuchi

Takayoshi Yamamoto

Kyoji Tomita

Mizuno Kazuhiro

Niga Toshiyuki

Ito Hideaki

Kashimoto Shigeki

Original Assignee

Dainippon Pharmaceutical Co

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.)

2002-08-23

Filing date

2003-08-22

Publication date

2004-07-01

2002-08-23 Priority claimed from JP2002242795A external-priority patent/JP2006052138A/ja

2002-11-22 Priority claimed from JP2002339200A external-priority patent/JP2006052139A/ja

2003-02-04 Priority claimed from JP2003027010A external-priority patent/JP2006052140A/ja

2003-08-22 Application filed by Dainippon Pharmaceutical Co filed Critical Dainippon Pharmaceutical Co

2004-07-01 Publication of TW200410956A publication Critical patent/TW200410956A/zh

Links

150000003147 proline derivatives Chemical class 0.000 title claims abstract description 23
150000001875 compounds Chemical class 0.000 claims abstract description 230
125000000217 alkyl group Chemical group 0.000 claims abstract description 68
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 54
150000003839 salts Chemical class 0.000 claims abstract description 45
125000004122 cyclic group Chemical group 0.000 claims abstract description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
125000005843 halogen group Chemical group 0.000 claims abstract description 17
229920006395 saturated elastomer Polymers 0.000 claims abstract description 17
229910052799 carbon Inorganic materials 0.000 claims abstract description 11
241000894006 Bacteria Species 0.000 claims abstract description 10
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
229910052736 halogen Inorganic materials 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
150000002367 halogens Chemical class 0.000 claims abstract description 3
-1 Proline derivative salt Chemical class 0.000 claims description 136
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 63
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 36
239000000203 mixture Substances 0.000 claims description 35
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 30
125000004429 atom Chemical group 0.000 claims description 28
125000003277 amino group Chemical group 0.000 claims description 27
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 15
239000003242 anti bacterial agent Substances 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 14
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
125000006239 protecting group Chemical group 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 11
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000005842 heteroatom Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
239000007789 gas Substances 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 4
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
239000000470 constituent Substances 0.000 claims description 4
239000007788 liquid Substances 0.000 claims description 4
229910052751 metal Chemical class 0.000 claims description 4
239000002184 metal Chemical class 0.000 claims description 4
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
150000005676 cyclic carbonates Chemical group 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
UPJFLBVSOWEZOE-UHFFFAOYSA-N n-(9h-fluoren-1-yl)hydroxylamine Chemical compound C1C2=CC=CC=C2C2=C1C(NO)=CC=C2 UPJFLBVSOWEZOE-UHFFFAOYSA-N 0.000 claims 2
239000000126 substance Substances 0.000 claims 2
150000003573 thiols Chemical class 0.000 claims 2
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical group N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims 1
125000003368 amide group Chemical group 0.000 claims 1
125000005872 benzooxazolyl group Chemical group 0.000 claims 1
230000001055 chewing effect Effects 0.000 claims 1
238000010586 diagram Methods 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000001183 hydrocarbyl group Chemical group 0.000 claims 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
125000003226 pyrazolyl group Chemical group 0.000 claims 1
125000000168 pyrrolyl group Chemical group 0.000 claims 1
NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 10
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 abstract description 3
230000000845 anti-microbial effect Effects 0.000 abstract 1
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 1
229910052727 yttrium Inorganic materials 0.000 abstract 1
238000005481 NMR spectroscopy Methods 0.000 description 169
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 71
238000004519 manufacturing process Methods 0.000 description 61
239000000243 solution Substances 0.000 description 49
238000000034 method Methods 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
239000013078 crystal Substances 0.000 description 42
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
229910052739 hydrogen Inorganic materials 0.000 description 40
239000002904 solvent Substances 0.000 description 34
238000002844 melting Methods 0.000 description 31
230000008018 melting Effects 0.000 description 31
238000000921 elemental analysis Methods 0.000 description 30
101150041968 CDC13 gene Proteins 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
238000006243 chemical reaction Methods 0.000 description 23
239000012044 organic layer Substances 0.000 description 23
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
238000003756 stirring Methods 0.000 description 17
238000001816 cooling Methods 0.000 description 16
238000010898 silica gel chromatography Methods 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
239000002994 raw material Substances 0.000 description 15
238000005160 1H NMR spectroscopy Methods 0.000 description 14
239000011575 calcium Substances 0.000 description 14
239000012043 crude product Substances 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
230000000844 anti-bacterial effect Effects 0.000 description 13
238000001914 filtration Methods 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-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
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
125000006242 amine protecting group Chemical group 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
239000013076 target substance Substances 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
208000015181 infectious disease Diseases 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
206010041925 Staphylococcal infections Diseases 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
238000001035 drying Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
241000191967 Staphylococcus aureus Species 0.000 description 5
239000000443 aerosol Substances 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229960000549 4-dimethylaminophenol Drugs 0.000 description 4
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
229940126062 Compound A Drugs 0.000 description 4
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
239000000499 gel Substances 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
235000013336 milk Nutrition 0.000 description 4
239000008267 milk Substances 0.000 description 4
210000004080 milk Anatomy 0.000 description 4
239000012046 mixed solvent Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000003396 thiol group Chemical group [H]S* 0.000 description 4
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
241000282414 Homo sapiens Species 0.000 description 3
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 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
241000191940 Staphylococcus Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
108010059993 Vancomycin Proteins 0.000 description 3
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
239000002504 physiological saline solution Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 3
229960003165 vancomycin Drugs 0.000 description 3
MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
XOETUHBIDWDVSF-UHFFFAOYSA-N 1-heptyl-2-phenylbenzene Chemical group CCCCCCCC1=CC=CC=C1C1=CC=CC=C1 XOETUHBIDWDVSF-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
102100025142 Beta-microseminoprotein Human genes 0.000 description 2
229910014033 C-OH Inorganic materials 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
229910014570 C—OH Inorganic materials 0.000 description 2
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VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
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238000010992 reflux Methods 0.000 description 1
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238000007363 ring formation reaction Methods 0.000 description 1
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WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
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XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

TW092123113A 2002-08-23 2003-08-22 Proline derivatives TW200410956A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
JP2002242795A JP2006052138A (ja)	2002-08-23	2002-08-23	プロリン誘導体
JP2002339200A JP2006052139A (ja)	2002-11-22	2002-11-22	プロリン誘導体
JP2003027010A JP2006052140A (ja)	2003-02-04	2003-02-04	プロリン誘導体

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TW200410956A true TW200410956A (en)	2004-07-01

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TW092123113A TW200410956A (en)	2002-08-23	2003-08-22	Proline derivatives

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AU (1)	AU2003257637A1 (fr)
TW (1)	TW200410956A (fr)
WO (1)	WO2004018453A1 (fr)

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EP1622569B1 (fr)	2003-04-24	2015-12-02	Incyte Corporation	Derives d'aza spiro alcane en tant qu'inhibiteurs de metalloproteases
AU2011265309B2 (en) *	2003-11-21	2014-06-05	Array Biopharma, Inc.	AKT protein kinase inhibitors
NZ590160A (en)	2003-11-21	2012-07-27	Array Biopharma Inc	AKT protein kinase inhibitors
JP4958560B2 (ja) *	2003-12-24	2012-06-20	プロシディオン・リミテッド	Ｇｐｃｒ受容体作動薬としてのヘテロ環誘導体
MX2007003318A (es) *	2004-09-20	2007-05-18	Xenon Pharmaceuticals Inc	Derivados heterociclicos y su uso como agentes terapeuticos.
NZ553734A (en) *	2004-09-20	2011-01-28	4Sc Ag	Novel thiazole derivatives as NF-kappaB inhibitors
EP1637529A1 (fr)	2004-09-20	2006-03-22	4Sc Ag	Nouveaux analogues de piperidin-4-yl-thiazole-carboxamide en tant qu'inhibiteurs de proliferation de lymphocytes T er leurs utilisations
US7601745B2 (en)	2004-09-27	2009-10-13	4Sc Ag	Heterocyclic NF-kB inhibitors
TW200738701A (en)	2005-07-26	2007-10-16	Du Pont	Fungicidal carboxamides
CN104119296A (zh) *	2013-04-25	2014-10-29	苏州科捷生物医药有限公司	一种2-三氟甲基-5-哌嗪基-噻二唑的合成方法

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DK1052984T3 (da) *	1998-02-07	2004-09-20	Vernalis Oxford Ltd	Antibakterielle midler
GB9907055D0 (en) *	1999-03-29	1999-05-19	British Biotech Pharm	Antibacterial agents
WO2002083628A1 (fr) *	2001-04-13	2002-10-24	Boehringer Ingelheim Pharmaceuticals, Inc.	Composes benzo-fusionnes a disubstitution en positions 1,4

2003
- 2003-08-21 WO PCT/JP2003/010548 patent/WO2004018453A1/fr not_active Ceased
- 2003-08-21 AU AU2003257637A patent/AU2003257637A1/en not_active Abandoned
- 2003-08-22 TW TW092123113A patent/TW200410956A/zh unknown

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WO2004018453A1 (fr)	2004-03-04
AU2003257637A1 (en)	2004-03-11

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