SE520026C2 - 2-amino-bicyclo/3.1.0/hexan-2, 6-dikarboxylsyraderivat och ett förfarande för framställning därav samt användning därav - Google Patents

2-amino-bicyclo/3.1.0/hexan-2, 6-dikarboxylsyraderivat och ett förfarande för framställning därav samt användning därav

Info

Publication number: SE520026C2
Authority: SE; Sweden
Prior art keywords: formula; hexane; dicarboxylic acid; bicyclo; compound
Prior art date: 1998-09-03

Application number

SE9903088A

Other languages

English (en)

Swedish (sv)

Other versions

SE9903088L (sv

SE9903088D0 (sv

Inventor

Geo Adam

Philippe Nic Huguenin-Virchaux

Vincent Mutel

Heinz Stadler

Thomas Johannes Woltering

Original Assignee

Hoffmann La Roche

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.)

1998-09-03

Filing date

1999-09-01

Publication date

2003-05-13

1999-09-01 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1999-09-01 Publication of SE9903088D0 publication Critical patent/SE9903088D0/xx

2000-03-04 Publication of SE9903088L publication Critical patent/SE9903088L/

2003-05-13 Publication of SE520026C2 publication Critical patent/SE520026C2/sv

Links

238000000034 method Methods 0.000 title claims abstract description 23
230000008569 process Effects 0.000 title claims abstract description 12
238000002360 preparation method Methods 0.000 title claims description 11
ANUFAWHRSIJTHW-UHFFFAOYSA-N 2-methylheptanedioic acid Chemical class OC(=O)C(C)CCCCC(O)=O ANUFAWHRSIJTHW-UHFFFAOYSA-N 0.000 title description 17
150000001875 compounds Chemical class 0.000 claims abstract description 85
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims abstract description 17
229910052722 tritium Inorganic materials 0.000 claims abstract description 17
239000001257 hydrogen Substances 0.000 claims abstract description 14
150000002431 hydrogen Chemical class 0.000 claims abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract 4
229910052805 deuterium Inorganic materials 0.000 claims abstract 4
125000003302 alkenyloxy group Chemical group 0.000 claims abstract 2
125000003545 alkoxy group Chemical group 0.000 claims abstract 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract 2
238000004519 manufacturing process Methods 0.000 claims abstract 2
-1 trifluoromethylsulfonic acid ester Chemical class 0.000 claims description 55
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
230000009467 reduction Effects 0.000 claims description 11
IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 9
125000004185 ester group Chemical group 0.000 claims description 9
239000007789 gas Substances 0.000 claims description 8
150000001540 azides Chemical class 0.000 claims description 7
230000001154 acute effect Effects 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
230000001684 chronic effect Effects 0.000 claims description 4
230000000926 neurological effect Effects 0.000 claims description 4
208000020016 psychiatric disease Diseases 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 3
239000002287 radioligand Substances 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
238000005574 benzylation reaction Methods 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
238000005984 hydrogenation reaction Methods 0.000 claims description 2
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
238000000159 protein binding assay Methods 0.000 claims description 2
238000012216 screening Methods 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
239000003814 drug Substances 0.000 claims 1
108010010914 Metabotropic glutamate receptors Proteins 0.000 abstract description 9
102000016193 Metabotropic glutamate receptors Human genes 0.000 abstract description 9
239000003446 ligand Substances 0.000 abstract description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
239000000243 solution Substances 0.000 description 71
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
WAGLGWVIZSFNGU-UHFFFAOYSA-N 1-o-benzyl 7-o-ethyl 2-methylheptanedioate Chemical compound CCOC(=O)CCCCC(C)C(=O)OCC1=CC=CC=C1 WAGLGWVIZSFNGU-UHFFFAOYSA-N 0.000 description 56
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 51
239000002904 solvent Substances 0.000 description 41
238000005160 1H NMR spectroscopy Methods 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
239000007787 solid Substances 0.000 description 31
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
239000000203 mixture Substances 0.000 description 23
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
238000010898 silica gel chromatography Methods 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
239000012267 brine Substances 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
239000003921 oil Substances 0.000 description 18
239000000047 product Substances 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
229920006395 saturated elastomer Polymers 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
ISFCQJNWQOFBGO-UHFFFAOYSA-N C(C)OC(=O)CCC=CC(C)C(=O)OCC1=CC=CC=C1 Chemical compound C(C)OC(=O)CCC=CC(C)C(=O)OCC1=CC=CC=C1 ISFCQJNWQOFBGO-UHFFFAOYSA-N 0.000 description 14
239000012043 crude product Substances 0.000 description 14
229910052763 palladium Inorganic materials 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
238000001816 cooling Methods 0.000 description 13
239000011734 sodium Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000003054 catalyst Substances 0.000 description 12
229910004373 HOAc Inorganic materials 0.000 description 11
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 11
229940024606 amino acid Drugs 0.000 description 10
150000001413 amino acids Chemical class 0.000 description 10
238000001914 filtration Methods 0.000 description 10
238000001035 drying Methods 0.000 description 9
239000012230 colorless oil Substances 0.000 description 8
150000001412 amines Chemical class 0.000 description 7
239000000010 aprotic solvent Substances 0.000 description 7
125000004122 cyclic group Chemical group 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
NIPUKWUNXZQBCO-UHFFFAOYSA-N 1-O-benzyl 7-O-ethyl 2-methylhept-2-enedioate Chemical compound C(C)OC(=O)CCCC=C(C)C(=O)OCC1=CC=CC=C1 NIPUKWUNXZQBCO-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
125000003342 alkenyl group Chemical group 0.000 description 6
230000000694 effects Effects 0.000 description 6
LFLSVOVPJVCWKQ-UHFFFAOYSA-N ethyl 2-methylhexanoate Chemical compound CCCCC(C)C(=O)OCC LFLSVOVPJVCWKQ-UHFFFAOYSA-N 0.000 description 6
229910052723 transition metal Inorganic materials 0.000 description 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
IEJSLSQHGVOPEE-UHFFFAOYSA-N 2-methylideneheptanedioic acid Chemical compound OC(=O)CCCCC(=C)C(O)=O IEJSLSQHGVOPEE-UHFFFAOYSA-N 0.000 description 5
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
LZXLPOGLQRPAAT-AZDHXYLBSA-N diazonio-[(1s,2r,3r,5r,6s)-2,6-dicarboxy-3-hydroxy-2-bicyclo[3.1.0]hexanyl]azanide Chemical compound [N-]=[N+]=N[C@@]1(C(O)=O)[C@H](O)C[C@H]2[C@H](C(O)=O)[C@H]21 LZXLPOGLQRPAAT-AZDHXYLBSA-N 0.000 description 5
KNHPIDSTNJTCOI-UHFFFAOYSA-N dimethyl 2-methylheptanedioate Chemical compound COC(=O)CCCCC(C)C(=O)OC KNHPIDSTNJTCOI-UHFFFAOYSA-N 0.000 description 5
MOTXKEQQXJIDHO-UHFFFAOYSA-N ethyl hept-3-enoate Chemical compound CCCC=CCC(=O)OCC MOTXKEQQXJIDHO-UHFFFAOYSA-N 0.000 description 5
150000003624 transition metals Chemical class 0.000 description 5
BLAOFNJKGKSGDI-FJNNMDBYSA-N (1s,2r,3s,5r,6s)-2,3-diaminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)[C@@H](N)C[C@H]2[C@H](C(O)=O)[C@H]21 BLAOFNJKGKSGDI-FJNNMDBYSA-N 0.000 description 4
XSGPNKMSSRGAOP-UHFFFAOYSA-N 2-O-benzyl 6-O-ethyl bicyclo[3.1.0]hexane-2,6-dicarboxylate Chemical compound C(C)OC(=O)C1C2CCC(C12)C(=O)OCC1=CC=CC=C1 XSGPNKMSSRGAOP-UHFFFAOYSA-N 0.000 description 4
HSDPSXBQFGFXJC-KEVRVKNQSA-N 2-o-benzyl 6-o-ethyl (1s,2r,3r,5r,6s)-2-amino-3-phenylmethoxybicyclo[3.1.0]hexane-2,6-dicarboxylate Chemical compound O([C@@H]1C[C@H]2[C@@H]([C@H]2[C@]1(N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC)CC1=CC=CC=C1 HSDPSXBQFGFXJC-KEVRVKNQSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 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
NTPXNEQCDPWJQA-WDSAACQFSA-N (1s,2r,3r,5r,6s)-2-amino-3-deuterio-3-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)[C@]([2H])(O)C[C@H]2[C@H](C(O)=O)[C@H]21 NTPXNEQCDPWJQA-WDSAACQFSA-N 0.000 description 3
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 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
229940049906 glutamate Drugs 0.000 description 3
229930195712 glutamate Natural products 0.000 description 3
239000000463 material Substances 0.000 description 3
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
239000012071 phase Substances 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
238000012546 transfer Methods 0.000 description 3
230000009466 transformation Effects 0.000 description 3
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
NTPXNEQCDPWJQA-MMMQMUATSA-N (1s,2r,3s,5r,6s)-2-amino-3-deuterio-3-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)[C@@]([2H])(O)C[C@H]2[C@H](C(O)=O)[C@H]21 NTPXNEQCDPWJQA-MMMQMUATSA-N 0.000 description 2
UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 2
HIYOHPIWPLVTHJ-QFNYKRGWSA-N 2-o-benzyl 6-o-ethyl (1s,2s,3r,6s)-2,3-dihydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate Chemical compound O=C([C@@]1(O)[C@H](O)CC2[C@@H]([C@@H]12)C(=O)OCC)OCC1=CC=CC=C1 HIYOHPIWPLVTHJ-QFNYKRGWSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
229910004664 Cerium(III) chloride Inorganic materials 0.000 description 2
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 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
229910052770 Uranium Inorganic materials 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
238000005341 cation exchange Methods 0.000 description 2
VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
238000005805 hydroxylation reaction Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
239000012528 membrane Substances 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
229910052697 platinum Inorganic materials 0.000 description 2
239000003586 protic polar solvent Substances 0.000 description 2
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000000523 sample Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012354 sodium borodeuteride Substances 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
239000011877 solvent mixture Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000000844 transformation Methods 0.000 description 2
YWWDBCBWQNCYNR-UHFFFAOYSA-N trimethylphosphine Chemical compound CP(C)C YWWDBCBWQNCYNR-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
238000000825 ultraviolet detection Methods 0.000 description 2
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
QAMRXJFPYSJIOA-GZXQVXQFSA-N (1s,2r,3r,5r,6s)-2-acetamido-3-deuterio-3-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound CC(=O)N[C@@]1(C(O)=O)[C@]([2H])(O)C[C@H]2[C@H](C(O)=O)[C@H]21 QAMRXJFPYSJIOA-GZXQVXQFSA-N 0.000 description 1
NTPXNEQCDPWJQA-FJNNMDBYSA-N (1s,2r,3s,5r,6s)-2-amino-3-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound C1[C@H](O)[C@@](N)(C(O)=O)[C@@H]2[C@@H](C(O)=O)[C@H]12 NTPXNEQCDPWJQA-FJNNMDBYSA-N 0.000 description 1
DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
AIRVPNIVQBTRRE-UHFFFAOYSA-N 2-o-benzyl 6-o-ethyl bicyclo[3.1.0]hex-2-ene-2,6-dicarboxylate Chemical compound C12C(C(=O)OCC)C2CC=C1C(=O)OCC1=CC=CC=C1 AIRVPNIVQBTRRE-UHFFFAOYSA-N 0.000 description 1
AXTIUBUBFIWKQC-UHFFFAOYSA-N 6-methyl-7-oxo-7-phenylmethoxyheptanoic acid Chemical compound C(C1=CC=CC=C1)OC(=O)C(C)CCCCC(=O)O AXTIUBUBFIWKQC-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000010444 Acidosis Diseases 0.000 description 1
241001233887 Ania Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
239000007848 Bronsted acid Substances 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000694440 Colpidium aqueous Species 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
101150030061 Eloc gene Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
102000004310 Ion Channels Human genes 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 1
102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
241000872931 Myoporum sandwicense Species 0.000 description 1
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
IHTBAGCSIAFYLG-UHFFFAOYSA-N O.O.O.[B] Chemical compound O.O.O.[B] IHTBAGCSIAFYLG-UHFFFAOYSA-N 0.000 description 1
101000924984 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) 3-dehydroquinate dehydratase Proteins 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
HUZCTWYDQIQZPM-UHFFFAOYSA-N benzyl 2,2,2-trichloroethanimidate Chemical compound ClC(Cl)(Cl)C(=N)OCC1=CC=CC=C1 HUZCTWYDQIQZPM-UHFFFAOYSA-N 0.000 description 1
NHPHSQKWQYLZSA-UHFFFAOYSA-N bicyclo[3.1.0]hexan-1-ol Chemical compound C1CCC2(O)C1C2 NHPHSQKWQYLZSA-UHFFFAOYSA-N 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000337 buffer salt Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Chemical class O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
229940125890 compound Ia Drugs 0.000 description 1
239000010730 cutting oil Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
IQWCYEKHEHDUFD-ONQKKCPMSA-N diazonio-[(1s,2r,3r,5r,6s)-2,6-dicarboxy-3-phenylmethoxy-2-bicyclo[3.1.0]hexanyl]azanide Chemical compound O([C@@H]1C[C@H]2[C@@H]([C@H]2[C@]1([N-][N+]#N)C(O)=O)C(=O)O)CC1=CC=CC=C1 IQWCYEKHEHDUFD-ONQKKCPMSA-N 0.000 description 1
LJOQGZACKSYWCH-UHFFFAOYSA-N dihydro quinine Natural products C1=C(OC)C=C2C(C(O)C3CC4CCN3CC4CC)=CC=NC2=C1 LJOQGZACKSYWCH-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
VTAARTQTOOYTES-RGDLXGNYSA-N eglumegad Chemical compound OC(=O)[C@]1(N)CC[C@H]2[C@H](C(O)=O)[C@@H]12 VTAARTQTOOYTES-RGDLXGNYSA-N 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution 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
230000005284 excitation Effects 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
238000007429 general method Methods 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 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
150000004678 hydrides Chemical class 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
150000002497 iodine compounds Chemical class 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
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
238000002386 leaching Methods 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
NRUBUZBAZRTHHX-UHFFFAOYSA-N lithium;propan-2-ylazanide Chemical compound [Li+].CC(C)[NH-] NRUBUZBAZRTHHX-UHFFFAOYSA-N 0.000 description 1
ORXVFYBFZLZLPL-UHFFFAOYSA-N lithium;trimethyl borate Chemical compound [Li].COB(OC)OC ORXVFYBFZLZLPL-UHFFFAOYSA-N 0.000 description 1
108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 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
LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
230000001242 postsynaptic effect Effects 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000003518 presynaptic effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
UJYZRNWTLPBNOR-UHFFFAOYSA-N prop-2-enyl 2,2,2-trichloroethanimidate Chemical compound ClC(Cl)(Cl)C(=N)OCC=C UJYZRNWTLPBNOR-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
150000003303 ruthenium Chemical class 0.000 description 1
YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000009991 second messenger activation Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
210000002265 sensory receptor cell Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000725 suspension Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
150000003649 tritium Chemical class 0.000 description 1
210000002268 wool Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/32—Preparation of optical isomers by stereospecific synthesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C229/50—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups and carboxyl groups bound to carbon atoms being part of the same condensed ring system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- C07C247/14—Compounds containing azido groups with azido groups bound to carbon atoms of rings other than six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/18—All rings being cycloaliphatic the ring system containing six carbon atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Cephalosporin Compounds (AREA)

SE9903088A 1998-09-03 1999-09-01 2-amino-bicyclo/3.1.0/hexan-2, 6-dikarboxylsyraderivat och ett förfarande för framställning därav samt användning därav SE520026C2 (sv)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP98116670		1998-09-03

Publications (3)

Publication Number	Publication Date
SE9903088D0 SE9903088D0 (sv)	1999-09-01
SE9903088L SE9903088L (sv)	2000-03-04
SE520026C2 true SE520026C2 (sv)	2003-05-13

Family

ID=8232576

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SE9903088A SE520026C2 (sv)	1998-09-03	1999-09-01	2-amino-bicyclo/3.1.0/hexan-2, 6-dikarboxylsyraderivat och ett förfarande för framställning därav samt användning därav

Country Status (13)

Country	Link
US (1)	US6107342A (de)
JP (1)	JP3340409B2 (de)
AT (1)	AT501853B1 (de)
AU (1)	AU757939B2 (de)
BE (1)	BE1014616A3 (de)
CA (1)	CA2281272C (de)
CH (1)	CH694053A5 (de)
DE (1)	DE19941675B4 (de)
FR (1)	FR2786768B1 (de)
GB (1)	GB2341179B (de)
IT (1)	IT1313618B1 (de)
NL (1)	NL1012963C2 (de)
SE (1)	SE520026C2 (de)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL208123B1 (pl) *	2001-12-27	2011-03-31	Taisho Pharmaceutical Co Ltd	Pochodna kwasu 2-amino-3-alkoksy-6-fluorobicyklo [3.1.0] heksano-2, 6-dikarboksylowego, zawierająca ją kompozycja farmaceutyczna i lek, oraz jej zastosowanie
US7381746B2 (en)	2003-06-26	2008-06-03	Taisho Pharmaceutical Co., Ltd.	2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative
JP2007063129A (ja) *	2003-06-26	2007-03-15	Taisho Pharmaceut Co Ltd	２−アミノ−３−アルコキシビシクロ［３．１．０］ヘキサン誘導体
RU2349580C2 (ru) *	2003-06-26	2009-03-20	Таишо Фармасьютикал Ко., Лтд	Сложноэфирное производное 2-амино-бицикло[3.1.0]гексан-2,6-дикарбоновой кислоты, обладающее свойствами антагониста метаботропных глутаматных рецепторов ii группы
EP2123630B1 (de) *	2003-06-26	2012-07-25	Taisho Pharmaceutical Co., Ltd	2-Aminobicyclo[3.1.0]hexan-2,6-dicarbonsäureesterderivat
CN100582087C (zh)	2003-06-26	2010-01-20	大正制药株式会社	2-氨基-双环[3.1.0]己烷-2,6-二甲酸酯衍生物
EP2275096A3 (de)	2005-08-26	2011-07-13	Braincells, Inc.	Neurogenese durch modulation des Muscarinrezeptors
US7301003B2 (en) *	2005-08-26	2007-11-27	Enzon Pharmaceuticals, Inc.	Method of preparing polymers having terminal amine groups
EP2258357A3 (de)	2005-08-26	2011-04-06	Braincells, Inc.	Neurogenese mit Acetylcholinesterasehemmer
WO2007047978A2 (en)	2005-10-21	2007-04-26	Braincells, Inc.	Modulation of neurogenesis by pde inhibition
EP2314289A1 (de)	2005-10-31	2011-04-27	Braincells, Inc.	Gaba-rezeptor-vermittelte modulation von neurogenese
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
AR059898A1 (es)	2006-03-15	2008-05-07	Janssen Pharmaceutica Nv	Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2
EP2021000A2 (de)	2006-05-09	2009-02-11	Braincells, Inc.	Neurogenese mittels angiotensin-modulation
US7678808B2 (en)	2006-05-09	2010-03-16	Braincells, Inc.	5 HT receptor mediated neurogenesis
WO2008030651A1 (en)	2006-09-08	2008-03-13	Braincells, Inc.	Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en)	2006-09-19	2010-07-22	Braincells, Inc.	Modulation of neurogenesis by ppar agents
TW200900065A (en)	2007-03-07	2009-01-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
TW200845978A (en) *	2007-03-07	2008-12-01	Janssen Pharmaceutica Nv	3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
EA017648B1 (ru)	2007-09-14	2013-02-28	Орто-Макнейл-Янссен Фармасьютикалз, Инк.	1',3'-двузамещенные-4-фенил-3,4,5,6-тетрагидро-2н,1'н-[1,4']бипириди-нил-2'-оны
BRPI0816970A2 (pt) *	2007-09-14	2015-03-24	Ortho Mcneil Janssen Pharm	1,3-dissubstituídas-4-fenil-1h-piridin-2-onas
TW200922566A (en)	2007-09-14	2009-06-01	Ortho Mcneil Janssen Pharm	1,3 disubstituted 4-(aryl-X-phenyl)-1H-pyridin-2-ones
CA2704436C (en) *	2007-11-14	2016-01-05	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	Imidazo[1,2-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
JP5547194B2 (ja)	2008-09-02	2014-07-09	ジャンセンファーマシューティカルズ，インコーポレイテッド．	代謝型グルタミン酸受容体の調節因子としての３−アザビシクロ［３．１．０］ヘキシル誘導体
WO2010043396A1 (en)	2008-10-16	2010-04-22	Ortho-Mcneil-Janssen Pharmaceuticals, Inc.	Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors
JP5690277B2 (ja)	2008-11-28	2015-03-25	ジャンセンファーマシューティカルズ，インコーポレイテッド．	代謝型グルタミン酸受容体の調節因子としてのインドールおよびベンゾオキサジン誘導体
US20100216805A1 (en)	2009-02-25	2010-08-26	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
CN102439015B (zh)	2009-05-12	2015-05-13	杨森制药有限公司	1,2,4-三唑并[4,3-a]吡啶衍生物和其作为mGluR2受体的正向变构调节剂的用途
MY153913A (en)	2009-05-12	2015-04-15	Janssen Pharmaceuticals Inc	7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
HRP20131122T1 (hr)	2009-05-12	2013-12-20	Janssen Pharmaceuticals, Inc.	Derivati 1,2,4-triazolo[4,3-a] piridina i njihova uporaba u lijeäśenju ili prevenciji neuroloških i psihijatrijskih poremeä†aja
ES2536433T3 (es)	2010-11-08	2015-05-25	Janssen Pharmaceuticals, Inc.	Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2
JP5852664B2 (ja)	2010-11-08	2016-02-03	ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド	１，２，４−トリアゾロ［４，３−ａ］ピリジン誘導体およびｍＧｌｕＲ２受容体のポジティブアロステリックモジュレーターとしてのそれらの使用
EP2661435B1 (de)	2010-11-08	2015-08-19	Janssen Pharmaceuticals, Inc.	1,2,4-triazol[4,3-a]pyridinderivate und ihre verwendung als positive allosterische mglur2-rezeptormodulatoren
CN103209954B (zh) *	2010-11-18	2015-09-02	伊莱利利公司	作为mGluR2/3拮抗剂的4-取代的-3-苄氧基-双环[3.1.0]己烷化合物
AR083845A1 (es)	2010-11-18	2013-03-27	Lilly Co Eli	COMPUESTOS 3-FENILSULFANILMETIL-BICICLO[3.1.0]HEXANO 4-SUSTITUIDOS COMO ANTAGONISTAS DE mGluR2/3
JO3368B1 (ar)	2013-06-04	2019-03-13	Janssen Pharmaceutica Nv	مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2
JO3367B1 (ar)	2013-09-06	2019-03-13	Janssen Pharmaceutica Nv	مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2
ME03518B (de)	2014-01-21	2020-04-20	Janssen Pharmaceutica Nv	Kombinationen mit positiven allosterischen modulatoren von metabotropem glutamatergen rezeptor vom subtyp 2 und deren verwendung
PL3096790T3 (pl)	2014-01-21	2020-01-31	Janssen Pharmaceutica, N.V.	Kombinacje zawierające pozytywne modulatory allosteryczne lub agonistów ortosterycznych metabotropowego receptora glutaminergicznego podtypu 2 i ich zastosowanie

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5321143A (en) *	1988-05-26	1994-06-14	Massachusetts Institute Of Technology	Ruthenium-catalyzed production of cyclic sulfates
PL182285B1 (pl) *	1994-08-12	2001-12-31	Lilly Co Eli	Syntetyczne aminokwasy oraz ich estry i srodki farmaceutyczne je zawierajace PL PL PL PL PL PL PL
IL118727A (en) *	1995-06-29	2003-01-12	Lilly Co Eli	(-)-2-spiro-5-hydantoinbicyclo [3.1.0] hexane-6-carboxylic acid, salts thereof and use thereof for the preparation of (+)-(2) aminobicyclo [3.1.0] hexane-2,6-dicarboxylic acid
WO1997017950A1 (en) *	1995-11-16	1997-05-22	Eli Lilly And Company	Shoulder prosthesis

1999
- 1999-08-24 CH CH01550/99A patent/CH694053A5/de not_active IP Right Cessation
- 1999-08-30 US US09/385,935 patent/US6107342A/en not_active Expired - Lifetime
- 1999-08-31 CA CA2281272A patent/CA2281272C/en not_active Expired - Fee Related
- 1999-08-31 JP JP24416799A patent/JP3340409B2/ja not_active Expired - Fee Related
- 1999-08-31 GB GB9920579A patent/GB2341179B/en not_active Expired - Fee Related
- 1999-09-01 IT IT1999MI001860A patent/IT1313618B1/it active
- 1999-09-01 SE SE9903088A patent/SE520026C2/sv not_active IP Right Cessation
- 1999-09-01 DE DE19941675A patent/DE19941675B4/de not_active Expired - Fee Related
- 1999-09-01 FR FR9910971A patent/FR2786768B1/fr not_active Expired - Fee Related
- 1999-09-02 NL NL1012963A patent/NL1012963C2/nl not_active IP Right Cessation
- 1999-09-02 AU AU47327/99A patent/AU757939B2/en not_active Ceased
- 1999-09-02 AT AT0151499A patent/AT501853B1/de not_active IP Right Cessation
- 1999-09-03 BE BE9900595A patent/BE1014616A3/fr not_active IP Right Cessation

Also Published As

Publication number	Publication date
IT1313618B1 (it)	2002-09-09
DE19941675A1 (de)	2000-03-09
FR2786768B1 (fr)	2004-10-15
GB9920579D0 (en)	1999-11-03
JP2000086597A (ja)	2000-03-28
CH694053A5 (de)	2004-06-30
ITMI991860A0 (it)	1999-09-01
US6107342A (en)	2000-08-22
NL1012963C2 (nl)	2003-10-23
FR2786768A1 (fr)	2000-06-09
SE9903088L (sv)	2000-03-04
GB2341179B (en)	2004-02-18
CA2281272A1 (en)	2000-03-03
NL1012963A1 (nl)	2000-03-06
AT501853A1 (de)	2006-11-15
CA2281272C (en)	2011-01-04
DE19941675B4 (de)	2013-01-17
GB2341179A (en)	2000-03-08
AT501853B1 (de)	2010-06-15
JP3340409B2 (ja)	2002-11-05
ITMI991860A1 (it)	2001-03-01
SE9903088D0 (sv)	1999-09-01
IE990737A1 (en)	2000-03-22
BE1014616A3 (fr)	2004-02-03
AU757939B2 (en)	2003-03-13
AU4732799A (en)	2000-03-16

Legal Events

Date	Code	Title	Description
2011-05-03	NUG	Patent has lapsed

Publication	Publication Date	Title
US6107342A (en)	2000-08-22	2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives and a process for the preparation thereof
Luly et al.	1988	A convenient stereoselective synthesis of 1, 2, 3-aminodiols from. alpha.-amino acids
Satoh et al.	2003	A novel method for the asymmetric synthesis of 4, 4-disubstituted 2-cyclopentenones from optically active 1-chlorovinyl p-tolyl sulfoxides and its application to the asymmetric total synthesis of (+)-α-cuparenone
Mori et al.	1994	Novel synthesis of nitrogen heterocycles using zirconium-promoted reductive cyclization
Craig et al.	1991	Intramolecular diels-alder reactions of sulphonyl-substituted trienes
Chrzanowska et al.	2004	Asymmetric synthesis of (R)-(+)-and (S)-(−)-2, 3-methylenedioxy-8-oxoberbine (gusanlung D)
Fernández et al.	1990	A useful synthesis of chiral Glyoxylates
CN103601706B (zh)	2015-07-01	一种合成天然产物Jaspine B异构体的方法
Agami et al.	2000	SN2′ Regio and Stereoselective Alkylation of Allylic and Propargylic Mesylates Linked to a N-Boc Oxazolidine using Organocuprates
Anwar et al.	2003	Pyrrolidinones derived from (S)-pyroglutamic acid: penmacric acid and analogues
AU2018340858B2 (en)	2023-11-02	Chiral auxiliaries and uses thereof
Mizutani et al.	2004	A formal synthesis of a muscarinic M1 receptor antagonist,(-)-TAN1251A
Breuning et al.	2008	Enantioselective total synthesis of the tricyclic 9-oxabispidine (1R, 2S, 9S)-11-methyl-13-oxa-7, 11-diazatricyclo [7.3. 1.02, 7] tridecane
Zhang et al.	2010	An enantioselective total synthesis of natural antibiotic marasin
Piacenza	1977	Nucleophilic substitution with inversion of alcohol configuration with the reagent complex triphenylphosphine-diethyl azodicarboxylate-carboxylic acid. A convenient preparation of epicholesterol
CN115181055B (zh)	2024-08-13	一种中间体消旋混合物的制备方法
Ripoche et al.	1999	Stereoselective Synthesis of Substituted Piperidines–Total Synthesis and Absolute Configurations of (+)‐and (–)‐Dienomycin C
JP2012520291A (ja)	2012-09-06	ラメルテオンの調製方法
IE84074B1 (en)	2005-11-30	2-Amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives and a process for preparation thereof
CN107459522B (zh)	2019-06-28	天然生物碱Lundurine A-C的制备方法
JP3609853B2 (ja)	2005-01-12	ビタミンｄ合成中間体の製造方法
KR20000049980A (ko)	2000-08-05	엘-무스콘의 광학활성 분리 정제 방법
WO2024103319A1 (zh)	2024-05-23	一种合成(1r,2s,5s)-6,6-二甲基-3-氮杂双环[3,1,0]己基-2-羧酸甲酯盐酸盐的方法
CN115448865A (zh)	2022-12-09	一种不对称合成塞曲西坦中间体的方法
Urbach et al.	0	ENANTIOSELECTIVE SYNTHESIS OF 1S, 35, 55-and lR. 3S. 5~-~-AZABICYCLO [~.~.~~ OCTANE-3-CARBOXYLIC ACID STARTING FROM L-SERINE