JP2001507231A - ベンゾジアゼピン−酢酸エステルのリパーゼによる酵素的分割 - Google Patents
ベンゾジアゼピン−酢酸エステルのリパーゼによる酵素的分割Info
- Publication number
- JP2001507231A JP2001507231A JP52974298A JP52974298A JP2001507231A JP 2001507231 A JP2001507231 A JP 2001507231A JP 52974298 A JP52974298 A JP 52974298A JP 52974298 A JP52974298 A JP 52974298A JP 2001507231 A JP2001507231 A JP 2001507231A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- benzodiazepine
- oxo
- tetrahydro
- alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 108090001060 Lipase Proteins 0.000 title abstract description 16
- 102000004882 Lipase Human genes 0.000 title abstract description 16
- 239000004367 Lipase Substances 0.000 title abstract description 16
- 235000019421 lipase Nutrition 0.000 title abstract description 15
- UROWRFYCWSNTOI-UHFFFAOYSA-N 2-(1H-1,2-benzodiazepin-3-yl)acetic acid Chemical class OC(=O)CC1=NNc2ccccc2C=C1 UROWRFYCWSNTOI-UHFFFAOYSA-N 0.000 title description 2
- 230000002255 enzymatic effect Effects 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 51
- 150000001875 compounds Chemical class 0.000 claims description 47
- -1 4 , 4'-Bipiperidin-1-yl Chemical group 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 108010031797 Candida antarctica lipase B Proteins 0.000 claims description 10
- 102100035140 Vitronectin Human genes 0.000 claims description 10
- 108010031318 Vitronectin Proteins 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 241001661345 Moesziomyces antarcticus Species 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- 102000008946 Fibrinogen Human genes 0.000 claims description 8
- 108010049003 Fibrinogen Proteins 0.000 claims description 8
- 239000005557 antagonist Substances 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229940012952 fibrinogen Drugs 0.000 claims description 8
- 101710098554 Lipase B Proteins 0.000 claims description 7
- USQCSFAOCPKJQV-JTQLQIEISA-N 2-[(2s)-7-iodo-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N1[C@@H](CC(O)=O)C(=O)N(C)CC2=CC(I)=CC=C21 USQCSFAOCPKJQV-JTQLQIEISA-N 0.000 claims description 6
- CLWDLBDPVUWYEW-JTQLQIEISA-N [(2s)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N1[C@@H](CC(O)=O)C(=O)N(C)CC2=CC=CC=C21 CLWDLBDPVUWYEW-JTQLQIEISA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 3
- 239000003431 cross linking reagent Substances 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- AOJYFCHNWYFMQP-UHFFFAOYSA-N 2-(3-oxo-1,2-dihydro-1,4-benzodiazepin-2-yl)acetic acid Chemical compound C1=NC(=O)C(CC(=O)O)NC2=CC=CC=C21 AOJYFCHNWYFMQP-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- NRXZLGJMWXXTOA-ZDUSSCGKSA-N 2-[(2s)-4-methyl-7-[(2-methylpropan-2-yl)oxycarbonyl]-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N1[C@@H](CC(O)=O)C(=O)N(C)CC2=CC(C(=O)OC(C)(C)C)=CC=C21 NRXZLGJMWXXTOA-ZDUSSCGKSA-N 0.000 claims 1
- OCJURJNFLYOSLL-UHFFFAOYSA-N methyl 2-(4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl)acetate Chemical compound C1N(C)C(=O)C(CC(=O)OC)NC2=CC=CC=C21 OCJURJNFLYOSLL-UHFFFAOYSA-N 0.000 claims 1
- CTNHEPMOYGIJTB-UHFFFAOYSA-N methyl 2-(7-iodo-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl)acetate Chemical compound C1N(C)C(=O)C(CC(=O)OC)NC2=CC=C(I)C=C21 CTNHEPMOYGIJTB-UHFFFAOYSA-N 0.000 claims 1
- OCJURJNFLYOSLL-LLVKDONJSA-N methyl 2-[(2r)-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetate Chemical compound C1N(C)C(=O)[C@@H](CC(=O)OC)NC2=CC=CC=C21 OCJURJNFLYOSLL-LLVKDONJSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 17
- BYTRSUQNZQHUTO-UHFFFAOYSA-N acetic acid 1H-1,2-benzodiazepine Chemical class C(C)(=O)O.N1N=CC=CC2=C1C=CC=C2 BYTRSUQNZQHUTO-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 102000004190 Enzymes Human genes 0.000 description 21
- 108090000790 Enzymes Proteins 0.000 description 21
- 229940088598 enzyme Drugs 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000004296 chiral HPLC Methods 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 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 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 4
- 108010084311 Novozyme 435 Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 150000001557 benzodiazepines Chemical class 0.000 description 3
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 2
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- DUMCJIQEKVEWRJ-UHFFFAOYSA-N 2-(1,2-benzodiazepin-2-yl)acetic acid Chemical compound OC(=O)CN1C=CC=C2C=CC=CC2=N1 DUMCJIQEKVEWRJ-UHFFFAOYSA-N 0.000 description 2
- IBPYPQBTYONHAX-UHFFFAOYSA-N 2-(1h-1,4-benzodiazepin-2-yl)-2-oxoacetic acid Chemical compound N1C(C(=O)C(=O)O)=CN=CC2=CC=CC=C21 IBPYPQBTYONHAX-UHFFFAOYSA-N 0.000 description 2
- UKHFOXCPJKIADP-JTQLQIEISA-N 2-[(2s)-7-bromo-4-methyl-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N1[C@@H](CC(O)=O)C(=O)N(C)CC2=CC(Br)=CC=C21 UKHFOXCPJKIADP-JTQLQIEISA-N 0.000 description 2
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 2
- PRNRUOJLUPUJDN-UHFFFAOYSA-N 4-piperidin-4-ylpiperidine Chemical compound C1CNCCC1C1CCNCC1 PRNRUOJLUPUJDN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 239000004925 Acrylic resin Substances 0.000 description 2
- 229920000178 Acrylic resin Polymers 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 101710098556 Lipase A Proteins 0.000 description 2
- 101710099648 Lysosomal acid lipase/cholesteryl ester hydrolase Proteins 0.000 description 2
- 102100026001 Lysosomal acid lipase/cholesteryl ester hydrolase Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 229940124008 Nectin antagonist Drugs 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 241000589540 Pseudomonas fluorescens Species 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 241000235527 Rhizopus Species 0.000 description 2
- 101150021948 SAM2 gene Proteins 0.000 description 2
- 229920002807 Thiomer Polymers 0.000 description 2
- 241000235015 Yarrowia lipolytica Species 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 150000002537 isoquinolines Chemical class 0.000 description 2
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical class N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical group N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-O 1-azoniabicyclo[2.2.2]octane Chemical compound C1CC2CC[NH+]1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-O 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- SXHPOBDTEYIZFL-UHFFFAOYSA-N 2-(1h-1,4-benzodiazepin-2-yl)acetic acid Chemical compound N1C(CC(=O)O)=CN=CC2=CC=CC=C21 SXHPOBDTEYIZFL-UHFFFAOYSA-N 0.000 description 1
- CCLBOAZTYCBGSI-UHFFFAOYSA-N 2-(1h-azepin-2-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC=CN1 CCLBOAZTYCBGSI-UHFFFAOYSA-N 0.000 description 1
- PYZOVVQJTLOHDG-FQEVSTJZSA-N 2-[(2s)-4-methyl-3-oxo-7-(4-piperidin-4-ylpiperidine-1-carbonyl)-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound O=C([C@H](CC(O)=O)NC1=CC=2)N(C)CC1=CC=2C(=O)N(CC1)CCC1C1CCNCC1 PYZOVVQJTLOHDG-FQEVSTJZSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000114726 Acetes Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 241001112078 Aspergillus usamii Species 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical group CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- DWVVXXSQTFPQGV-UHFFFAOYSA-N C(C)(=O)O.O=C1C=NC2=C(C=N1)C=CC=C2 Chemical compound C(C)(=O)O.O=C1C=NC2=C(C=N1)C=CC=C2 DWVVXXSQTFPQGV-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- PYTBVVSRIPWGCD-UHFFFAOYSA-N CN1CC2=C(C=CC(=C2)I)N(CC1=O)C Chemical compound CN1CC2=C(C=CC(=C2)I)N(CC1=O)C PYTBVVSRIPWGCD-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GVOUFPWUYJWQSK-UHFFFAOYSA-N Cyclofenil Chemical group C1=CC(OC(=O)C)=CC=C1C(C=1C=CC(OC(C)=O)=CC=1)=C1CCCCC1 GVOUFPWUYJWQSK-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 229940122331 Fibrinogen antagonist Drugs 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 244000168141 Geotrichum candidum Species 0.000 description 1
- 235000017388 Geotrichum candidum Nutrition 0.000 description 1
- 101700012268 Holin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 240000000064 Penicillium roqueforti Species 0.000 description 1
- 235000002233 Penicillium roqueforti Nutrition 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000005384 Rhizopus oryzae Species 0.000 description 1
- 235000013752 Rhizopus oryzae Nutrition 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010056079 Subtilisins Proteins 0.000 description 1
- 102000005158 Subtilisins Human genes 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 241000223258 Thermomyces lanuginosus Species 0.000 description 1
- 108010048673 Vitronectin Receptors Proteins 0.000 description 1
- VJMAITQRABEEKP-UHFFFAOYSA-N [6-(phenylmethoxymethyl)-1,4-dioxan-2-yl]methyl acetate Chemical compound O1C(COC(=O)C)COCC1COCC1=CC=CC=C1 VJMAITQRABEEKP-UHFFFAOYSA-N 0.000 description 1
- 241000179532 [Candida] cylindracea Species 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- ZYXVUJHYDUORFN-UHFFFAOYSA-N benzyl 4-piperidin-4-ylpiperidine-1-carboxylate Chemical compound C1CC(C2CCNCC2)CCN1C(=O)OCC1=CC=CC=C1 ZYXVUJHYDUORFN-UHFFFAOYSA-N 0.000 description 1
- ARXIJONEANSTJY-UHFFFAOYSA-N benzyl 4-piperidin-4-ylpiperidine-1-carboxylate;hydrochloride Chemical compound Cl.C1CC(C2CCNCC2)CCN1C(=O)OCC1=CC=CC=C1 ARXIJONEANSTJY-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical group ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- FRTGEIHSCHXMTI-UHFFFAOYSA-N dimethyl octanediimidate Chemical compound COC(=N)CCCCCCC(=N)OC FRTGEIHSCHXMTI-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 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 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- IZXGWMZZBYDCCF-UHFFFAOYSA-N methyl 2-[4-methyl-3-oxo-7-(4-piperidin-4-ylpiperidine-1-carbonyl)-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetate Chemical compound C1=C2CN(C)C(=O)C(CC(=O)OC)NC2=CC=C1C(=O)N(CC1)CCC1C1CCNCC1 IZXGWMZZBYDCCF-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005188 oxoalkyl group Chemical group 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- NERBLCVCQKXTEP-UHFFFAOYSA-N tert-butyl 4-piperidin-4-ylpiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1CCNCC1 NERBLCVCQKXTEP-UHFFFAOYSA-N 0.000 description 1
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
- C12P17/165—Heterorings having nitrogen atoms as the only ring heteroatoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3385396P | 1996-12-27 | 1996-12-27 | |
| US60/033,853 | 1996-12-27 | ||
| PCT/GB1997/003522 WO1998029561A1 (en) | 1996-12-27 | 1997-12-23 | Enzymatic resolution of benzodiazepine-acetic acid esters with a lipase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001507231A true JP2001507231A (ja) | 2001-06-05 |
Family
ID=21872833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52974298A Pending JP2001507231A (ja) | 1996-12-27 | 1997-12-23 | ベンゾジアゼピン−酢酸エステルのリパーゼによる酵素的分割 |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0964928A1 (xx) |
| JP (1) | JP2001507231A (xx) |
| KR (1) | KR20000069705A (xx) |
| CN (1) | CN1246157A (xx) |
| AR (1) | AR010860A1 (xx) |
| AU (1) | AU730064B2 (xx) |
| BR (1) | BR9714099A (xx) |
| CA (1) | CA2276134A1 (xx) |
| CO (1) | CO4930272A1 (xx) |
| HU (1) | HUP0002825A3 (xx) |
| IL (1) | IL130580A0 (xx) |
| NO (1) | NO993174L (xx) |
| NZ (1) | NZ336376A (xx) |
| PL (1) | PL334293A1 (xx) |
| TR (1) | TR199901487T2 (xx) |
| WO (1) | WO1998029561A1 (xx) |
| ZA (1) | ZA9711566B (xx) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006524043A (ja) * | 2003-04-04 | 2006-10-26 | ソルヴェイ | エナンチオ純粋β−アミノ酸誘導体の製造方法、及びエナンチオ純粋β−アミノ酸誘導体 |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1054996B1 (en) | 1998-02-17 | 2004-01-28 | G.D. SEARLE & CO. | Process for the enzymatic resolution of lactams |
| CA2410438A1 (en) * | 2000-06-01 | 2001-12-06 | Sk Corporation | Method for optically resolving a racemic alpha-substituted heterocyclic carboxylic acid using enzyme |
| KR100378741B1 (ko) * | 2000-06-01 | 2003-04-07 | 에스케이 주식회사 | 효소를 이용하여 R-폼 또는 S-폼의 α-치환 헤테로싸이클릭 카르복실산 및 이와 상반되는 광학특성을 갖는 α-치환 헤테로싸이클릭 카르복실산 에스테르를 제조하는 방법 |
| KR100379756B1 (ko) * | 2000-10-02 | 2003-04-11 | 한국과학기술연구원 | 이성질체 분할방법 |
| US6828119B2 (en) * | 2001-01-04 | 2004-12-07 | Bristol Myers Squibb Company | Enzymatic deprotection of amines and hydroxides |
| KR100650798B1 (ko) * | 2004-07-19 | 2006-11-27 | (주)제이코통상 | 광학활성 카복실산의 제조방법 |
| FR2876102A1 (fr) * | 2004-10-04 | 2006-04-07 | Solvay | Compose heterocyclique enantiopur |
| KR100650797B1 (ko) * | 2005-12-12 | 2006-11-27 | (주)케미코월드 | 광학활성 사이클로프로판 카복사미드의 제조방법 |
| FR2986804A1 (fr) * | 2012-02-09 | 2013-08-16 | Servier Lab | Procede de synthese enzymatique de l'acide (7s) 3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene 7-carboxylique ou de ses esters, et application a la synthese de l'ivabradine et de ses sels |
| CN117363683A (zh) * | 2023-10-09 | 2024-01-09 | 江苏惠利生物科技有限公司 | 一种脂酶苯并二氮杂-乙酸酯的酶拆分方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3497164B2 (ja) * | 1991-06-28 | 2004-02-16 | スミスクライン・ビーチャム・コーポレイション | 二環式フィブリノーゲン拮抗薬 |
| NZ259802A (en) * | 1992-12-21 | 1997-10-24 | Smithkline Beecham Corp | Bicyclic derivatives and pharmaceutical compositions |
| MA23420A1 (fr) * | 1994-01-07 | 1995-10-01 | Smithkline Beecham Corp | Antagonistes bicycliques de fibrinogene. |
| US5529929A (en) * | 1995-06-07 | 1996-06-25 | Seprachem, Inc. | Optical resolution of alkyl 1,4-benzodioxan-2-carboxylates using esterase from serratia marcescens |
-
1997
- 1997-12-23 CA CA002276134A patent/CA2276134A1/en not_active Abandoned
- 1997-12-23 ZA ZA9711566A patent/ZA9711566B/xx unknown
- 1997-12-23 WO PCT/GB1997/003522 patent/WO1998029561A1/en not_active Application Discontinuation
- 1997-12-23 HU HU0002825A patent/HUP0002825A3/hu unknown
- 1997-12-23 JP JP52974298A patent/JP2001507231A/ja active Pending
- 1997-12-23 KR KR1019997005777A patent/KR20000069705A/ko not_active Application Discontinuation
- 1997-12-23 TR TR1999/01487T patent/TR199901487T2/xx unknown
- 1997-12-23 IL IL13058097A patent/IL130580A0/xx unknown
- 1997-12-23 EP EP97950309A patent/EP0964928A1/en not_active Withdrawn
- 1997-12-23 BR BR9714099A patent/BR9714099A/pt not_active IP Right Cessation
- 1997-12-23 AR ARP970106167A patent/AR010860A1/es not_active Application Discontinuation
- 1997-12-23 AU AU53314/98A patent/AU730064B2/en not_active Ceased
- 1997-12-23 PL PL97334293A patent/PL334293A1/xx unknown
- 1997-12-23 NZ NZ336376A patent/NZ336376A/xx unknown
- 1997-12-23 CN CN97181853A patent/CN1246157A/zh active Pending
- 1997-12-26 CO CO97075096A patent/CO4930272A1/es unknown
-
1999
- 1999-06-25 NO NO993174A patent/NO993174L/no not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006524043A (ja) * | 2003-04-04 | 2006-10-26 | ソルヴェイ | エナンチオ純粋β−アミノ酸誘導体の製造方法、及びエナンチオ純粋β−アミノ酸誘導体 |
| JP4712688B2 (ja) * | 2003-04-04 | 2011-06-29 | ソルヴェイ（ソシエテ アノニム） | エナンチオ純粋β−アミノ酸誘導体の製造方法、及びエナンチオ純粋β−アミノ酸誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA9711566B (en) | 1998-06-29 |
| AR010860A1 (es) | 2000-07-12 |
| NO993174D0 (no) | 1999-06-25 |
| PL334293A1 (en) | 2000-02-14 |
| EP0964928A1 (en) | 1999-12-22 |
| KR20000069705A (ko) | 2000-11-25 |
| HUP0002825A2 (hu) | 2000-12-28 |
| NZ336376A (en) | 2000-11-24 |
| CN1246157A (zh) | 2000-03-01 |
| TR199901487T2 (xx) | 1999-11-22 |
| CA2276134A1 (en) | 1998-07-09 |
| NO993174L (no) | 1999-06-25 |
| BR9714099A (pt) | 2000-03-21 |
| AU730064B2 (en) | 2001-02-22 |
| CO4930272A1 (es) | 2000-06-27 |
| WO1998029561A1 (en) | 1998-07-09 |
| HUP0002825A3 (en) | 2002-09-30 |
| AU5331498A (en) | 1998-07-31 |
| IL130580A0 (en) | 2000-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2001507231A (ja) | ベンゾジアゼピン−酢酸エステルのリパーゼによる酵素的分割 | |
| US6133446A (en) | Heterocyclic compounds for the treatment of CNS and cardiovascular disorders | |
| CA2141843A1 (en) | Method of preparing optically pure precursors of paroxetine | |
| JP5973459B2 (ja) | ネビボロールの調製のための方法 | |
| WO2012059830A1 (en) | Manufacturing process for (s)-pregabalin | |
| JPH11501943A (ja) | カルビノールを分離する方法 | |
| HU199125B (en) | Process for producing benzazepine derivatives | |
| US5770438A (en) | Process for enantioselective hydrolysis of α-(2-amino)-phenyl-benzenemethanol ester type compounds using bacillus, pseudomonas or streptomyces | |
| EP1206452B1 (fr) | Procede de preparation de composes benzoperhydroisoindole | |
| JP2002514222A (ja) | 新規方法 | |
| EP1700851B1 (en) | Crystalline citalopram diol intermediate alkali | |
| KR19980702883A (ko) | 2,3-디히드로-벤조푸라놀 유도체의 신규 제조 방법 | |
| KR20080046630A (ko) | Ａｃｅ 저해제 트란돌라프릴의 제조방법 | |
| US5936098A (en) | Process for producing indoline compounds and intermediates for the production of the same | |
| EP1532146B1 (en) | A method of preparing enantiomers of indole-2,3-dione-3-oxime derivatives | |
| JP2002512807A (ja) | （−）−３．４−トランス−ジアリールクロマンを得るための酵素的分割 | |
| IE54878B1 (en) | 3,3-dialkyl- and 3,3-alkylene-indoline derivatives, processes for their production and pharmaceutical compositions comprising them | |
| JP2006503011A5 (xx) | ||
| EP2196458A1 (en) | Process for obtaining enantiomerically enriched pyrazole derivatives | |
| MXPA99006070A (en) | Enzymatic resolution of benzodiazepine-acetic acid esters with a lipase | |
| CZ229399A3 (cs) | Způsob enzymatického štěpení esterů kyseliny benzodiazepinoctové lipázou | |
| US5037987A (en) | Production of optical isomers of certain 1,6-naphthyridine-3-carboxylate derivatives | |
| CN1946854A (zh) | 制备依他普仑的化学－酶法 | |
| CN1054882C (zh) | 立体选择性制备杂二环醇对映体的酶促方法 | |
| US6184005B1 (en) | Enzymatic resolvation for obtaining a (−)-3,4-trans-diarylchroman |