IL136864A - METHOD FOR PREPARING TETHYDROBENZOTHYAPINE ENTIENTOMERALLY ENHANCED OXIDES - Google Patents

METHOD FOR PREPARING TETHYDROBENZOTHYAPINE ENTIENTOMERALLY ENHANCED OXIDES

Info

Publication number: IL136864A
Authority: IL; Israel
Prior art keywords: group; quaternary; independently selected; formula; heterocycle
Prior art date: 1997-12-19

Application number

IL13686498A

Other languages

English (en)

Hebrew (he)

Other versions

IL136864A0 (en

Original Assignee

Searle & 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.)

1997-12-19

Filing date

1998-12-16

Publication date

2004-07-25

1998-12-16 Application filed by Searle & Co filed Critical Searle & Co

2001-06-14 Publication of IL136864A0 publication Critical patent/IL136864A0/xx

2004-07-25 Publication of IL136864A publication Critical patent/IL136864A/en

Links

238000000034 method Methods 0.000 title claims abstract description 88
OETQCLHKWUINEL-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1$l^{4}-benzothiepine 1-oxide Chemical class O=S1CCCCC2=CC=CC=C12 OETQCLHKWUINEL-UHFFFAOYSA-N 0.000 title abstract description 4
125000004122 cyclic group Chemical group 0.000 claims abstract description 33
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 24
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 24
125000003118 aryl group Chemical group 0.000 claims abstract description 21
125000000217 alkyl group Chemical group 0.000 claims abstract description 19
229910052717 sulfur Inorganic materials 0.000 claims abstract description 19
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 17
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
125000001424 substituent group Chemical group 0.000 claims abstract description 17
239000011593 sulfur Substances 0.000 claims abstract description 17
-1 ammoniumalkyl Chemical group 0.000 claims abstract description 15
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
229910052799 carbon Chemical group 0.000 claims abstract description 12
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 11
239000001257 hydrogen Substances 0.000 claims abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
239000004721 Polyphenylene oxide Substances 0.000 claims abstract description 6
229920000570 polyether Polymers 0.000 claims abstract description 6
150000001450 anions Chemical class 0.000 claims abstract description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
125000003710 aryl alkyl group Chemical group 0.000 claims abstract 6
125000004104 aryloxy group Chemical group 0.000 claims abstract 5
125000004946 alkenylalkyl group Chemical group 0.000 claims abstract 2
125000004744 butyloxycarbonyl group Chemical group 0.000 claims abstract 2
230000003647 oxidation Effects 0.000 claims description 40
238000007254 oxidation reaction Methods 0.000 claims description 40
150000001875 compounds Chemical class 0.000 claims description 24
230000001590 oxidative effect Effects 0.000 claims description 20
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
SJGALSBBFTYSBA-UHFFFAOYSA-N oxaziridine Chemical compound C1NO1 SJGALSBBFTYSBA-UHFFFAOYSA-N 0.000 claims description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
239000011591 potassium Substances 0.000 claims description 6
229910052700 potassium Inorganic materials 0.000 claims description 6
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 5
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 5
239000010936 titanium Substances 0.000 claims description 5
229910052719 titanium Inorganic materials 0.000 claims description 5
239000007800 oxidant agent Substances 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 3
150000003462 sulfoxides Chemical class 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims 4
101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 claims 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 1
SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 claims 1
229910052804 chromium Inorganic materials 0.000 claims 1
239000011651 chromium Substances 0.000 claims 1
150000004696 coordination complex Chemical class 0.000 claims 1
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims 1
125000003342 alkenyl group Chemical group 0.000 abstract description 16
125000000304 alkynyl group Chemical group 0.000 abstract description 15
125000000753 cycloalkyl group Chemical group 0.000 abstract description 15
125000004432 carbon atom Chemical group C* 0.000 abstract description 4
125000004181 carboxyalkyl group Chemical group 0.000 abstract description 3
150000001768 cations Chemical class 0.000 abstract description 3
125000005038 alkynylalkyl group Chemical group 0.000 abstract description 2
150000002431 hydrogen Chemical class 0.000 abstract description 2
229910052760 oxygen Inorganic materials 0.000 abstract description 2
125000003545 alkoxy group Chemical group 0.000 abstract 3
125000001188 haloalkyl group Chemical group 0.000 abstract 3
125000004043 oxo group Chemical group O=* 0.000 abstract 3
101100160255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YLR154C-H gene Proteins 0.000 abstract 2
229910052736 halogen Inorganic materials 0.000 abstract 2
125000001475 halogen functional group Chemical group 0.000 abstract 2
150000002367 halogens Chemical group 0.000 abstract 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
101150020251 NR13 gene Proteins 0.000 abstract 1
125000002252 acyl group Chemical group 0.000 abstract 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 abstract 1
125000004966 cyanoalkyl group Chemical group 0.000 abstract 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 abstract 1
239000000243 solution Substances 0.000 description 66
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
238000002360 preparation method Methods 0.000 description 29
239000000047 product Substances 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 10
235000019439 ethyl acetate Nutrition 0.000 description 10
239000007787 solid Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
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 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
239000003613 bile acid Substances 0.000 description 6
239000010779 crude oil Substances 0.000 description 6
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
238000011282 treatment Methods 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 5
GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 5
239000002253 acid Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
238000004296 chiral HPLC Methods 0.000 description 5
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 5
239000007789 gas Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
230000008707 rearrangement Effects 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
238000001228 spectrum Methods 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-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
239000006185 dispersion Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
235000010446 mineral oil Nutrition 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
208000024172 Cardiovascular disease Diseases 0.000 description 3
208000035150 Hypercholesterolemia Diseases 0.000 description 3
229940125922 IBAT inhibitor Drugs 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
239000003814 drug Substances 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000003921 oil Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
238000011321 prophylaxis Methods 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
OXIQCJDVMBRASN-UHFFFAOYSA-N 3-(3-hydroxypropylsulfinyl)propan-1-ol Chemical compound OCCCS(=O)CCCO OXIQCJDVMBRASN-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000004803 chlorobenzyl group Chemical group 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
239000000284 extract Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000010992 reflux Methods 0.000 description 2
YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 description 1
CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 description 1
KZPHSSFCYARZCD-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzothiepine Chemical compound S1CCCCC2=CC=CC=C21 KZPHSSFCYARZCD-UHFFFAOYSA-N 0.000 description 1
HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
QRQVZZMTKYXEKC-UHFFFAOYSA-N 3-(3-hydroxypropylsulfanyl)propan-1-ol Chemical compound OCCCSCCCO QRQVZZMTKYXEKC-UHFFFAOYSA-N 0.000 description 1
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 1
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical class CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000005024 alkenyl aryl group Chemical group 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000006242 amine protecting group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
RSWXSRRFPFDSJS-UHFFFAOYSA-N carbamothioic s-acid Chemical compound NC(S)=O.NC(S)=O RSWXSRRFPFDSJS-UHFFFAOYSA-N 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000013553 cell monolayer Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical compound CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000002432 hydroperoxides Chemical class 0.000 description 1
230000000871 hypocholesterolemic effect Effects 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
SNHMUERNLJLMHN-IDEBNGHGSA-N iodobenzene Chemical group I[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 SNHMUERNLJLMHN-IDEBNGHGSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
ZHVULPDNOFUIML-UHFFFAOYSA-N octane;hydrochloride Chemical compound Cl.CCCCCCCC ZHVULPDNOFUIML-UHFFFAOYSA-N 0.000 description 1
150000004843 oxaziridines Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
239000013579 wash concentrate Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Epoxy Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

IL13686498A 1997-12-19 1998-12-16 METHOD FOR PREPARING TETHYDROBENZOTHYAPINE ENTIENTOMERALLY ENHANCED OXIDES IL136864A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US6817097P	1997-12-19	1997-12-19
PCT/US1998/026216 WO1999032478A1 (en)	1997-12-19	1998-12-16	Method of preparing enantiomerically-enriched tetrahydrobenzothiepine oxides

Publications (2)

Publication Number	Publication Date
IL136864A0 IL136864A0 (en)	2001-06-14
IL136864A true IL136864A (en)	2004-07-25

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IL13686498A IL136864A (en)	1997-12-19	1998-12-16	METHOD FOR PREPARING TETHYDROBENZOTHYAPINE ENTIENTOMERALLY ENHANCED OXIDES

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Country	Link
US (2)	US6369220B1 (de)
EP (1)	EP1042314B1 (de)
JP (1)	JP2001526284A (de)
KR (1)	KR20010015884A (de)
CN (2)	CN1106395C (de)
AT (1)	ATE234829T1 (de)
AU (1)	AU1721399A (de)
BR (1)	BR9814300A (de)
DE (1)	DE69812419T2 (de)
DK (1)	DK1042314T3 (de)
ES (1)	ES2195428T3 (de)
HU (1)	HUP0101193A3 (de)
IL (1)	IL136864A (de)
PT (1)	PT1042314E (de)
RU (1)	RU2236406C2 (de)
UA (1)	UA67764C2 (de)
WO (1)	WO1999032478A1 (de)
ZA (1)	ZA9811648B (de)

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1998
- 1998-12-16 AT AT98962044T patent/ATE234829T1/de not_active IP Right Cessation
- 1998-12-16 EP EP98962044A patent/EP1042314B1/de not_active Expired - Lifetime
- 1998-12-16 PT PT98962044T patent/PT1042314E/pt unknown
- 1998-12-16 UA UA2000074377A patent/UA67764C2/uk unknown
- 1998-12-16 AU AU17213/99A patent/AU1721399A/en not_active Abandoned
- 1998-12-16 RU RU2000119611/04A patent/RU2236406C2/ru not_active IP Right Cessation
- 1998-12-16 ES ES98962044T patent/ES2195428T3/es not_active Expired - Lifetime
- 1998-12-16 JP JP2000525415A patent/JP2001526284A/ja active Pending
- 1998-12-16 DK DK98962044T patent/DK1042314T3/da active
- 1998-12-16 WO PCT/US1998/026216 patent/WO1999032478A1/en not_active Ceased
- 1998-12-16 KR KR1020007006795A patent/KR20010015884A/ko not_active Ceased
- 1998-12-16 HU HU0101193A patent/HUP0101193A3/hu unknown
- 1998-12-16 US US09/581,897 patent/US6369220B1/en not_active Expired - Fee Related
- 1998-12-16 BR BR9814300-0A patent/BR9814300A/pt not_active IP Right Cessation
- 1998-12-16 IL IL13686498A patent/IL136864A/en not_active IP Right Cessation
- 1998-12-16 DE DE69812419T patent/DE69812419T2/de not_active Expired - Fee Related
- 1998-12-16 CN CN98813609A patent/CN1106395C/zh not_active Expired - Fee Related
- 1998-12-18 ZA ZA9811648A patent/ZA9811648B/xx unknown
2002
- 2002-02-11 US US10/072,600 patent/US6875877B2/en not_active Expired - Fee Related
2003
- 2003-02-28 CN CN03107046A patent/CN1439638A/zh active Pending

Also Published As

Publication number	Publication date
DE69812419T2 (de)	2003-08-14
IL136864A0 (en)	2001-06-14
HUP0101193A3 (en)	2001-12-28
HK1034971A1 (en)	2001-11-09
WO1999032478A1 (en)	1999-07-01
HUP0101193A2 (hu)	2001-08-28
US20020188119A1 (en)	2002-12-12
BR9814300A (pt)	2002-02-05
EP1042314A1 (de)	2000-10-11
CN1106395C (zh)	2003-04-23
DE69812419D1 (de)	2003-04-24
EP1042314B1 (de)	2003-03-19
DK1042314T3 (da)	2003-07-14
KR20010015884A (ko)	2001-02-26
US6369220B1 (en)	2002-04-09
ATE234829T1 (de)	2003-04-15
ZA9811648B (en)	1999-12-20
US6875877B2 (en)	2005-04-05
ES2195428T3 (es)	2003-12-01
RU2236406C2 (ru)	2004-09-20
AU1721399A (en)	1999-07-12
CN1284953A (zh)	2001-02-21
JP2001526284A (ja)	2001-12-18
PT1042314E (pt)	2003-07-31
CN1439638A (zh)	2003-09-03
UA67764C2 (uk)	2004-07-15

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Date	Code	Title
2004-12-15	FF	Patent granted
2005-02-20	KB	Patent renewed
2010-04-08	MM9K	Patent not in force due to non-payment of renewal fees

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IL136864A (en)	2004-07-25	METHOD FOR PREPARING TETHYDROBENZOTHYAPINE ENTIENTOMERALLY ENHANCED OXIDES
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