CA1091652A - Derives dipeptidiques et procede de production - Google Patents

Derives dipeptidiques et procede de production

Info

Publication number: CA1091652A
Authority: CA; Canada
Prior art keywords: group; chloro; methyl; hydrogen; ring
Prior art date: 1974-08-06
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.): Expired

Application number

CA339,232A

Other languages

English (en)

Inventor

Kentaro Hirai

Teruyuki Ishiba

Kazuyuki Sasakura

Hirohiko Sugimoto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Shionogi and Co Ltd

Original Assignee

Shionogi and Co Ltd

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.)

1974-08-06

Filing date

1979-11-06

Publication date

1980-12-16

1974-08-06 Priority claimed from JP49090566A external-priority patent/JPS605599B2/ja

1974-08-06 Priority claimed from JP49090565A external-priority patent/JPS604199B2/ja

1975-07-31 Priority claimed from CA000232782A external-priority patent/CA1181065A/fr

1979-11-06 Application filed by Shionogi and Co Ltd filed Critical Shionogi and Co Ltd

1979-11-06 Priority to CA339,232A priority Critical patent/CA1091652A/fr

1980-12-16 Application granted granted Critical

1980-12-16 Publication of CA1091652A publication Critical patent/CA1091652A/fr

Status Expired legal-status Critical Current

Links

238000004519 manufacturing process Methods 0.000 title claims description 3
108010016626 Dipeptides Proteins 0.000 title abstract description 10
-1 glycylglycyl group Chemical group 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
239000001257 hydrogen Substances 0.000 claims abstract description 51
150000001875 compounds Chemical class 0.000 claims abstract description 44
229910052736 halogen Inorganic materials 0.000 claims abstract description 23
150000002367 halogens Chemical group 0.000 claims abstract description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims abstract description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
125000004966 cyanoalkyl group Chemical group 0.000 claims abstract description 10
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 8
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims abstract description 6
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 4
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 11
150000005171 halobenzenes Chemical group 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 33
150000002431 hydrogen Chemical group 0.000 claims description 26
239000000460 chlorine Substances 0.000 claims description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 19
238000006664 bond formation reaction Methods 0.000 claims description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 13
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 9
150000002332 glycine derivatives Chemical class 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 6
108090000765 processed proteins & peptides Proteins 0.000 claims description 6
MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 5
230000001590 oxidative effect Effects 0.000 claims description 5
125000005544 phthalimido group Chemical group 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
239000003513 alkali Substances 0.000 claims description 4
150000001413 amino acids Chemical class 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 4
239000011737 fluorine Chemical group 0.000 claims description 4
229910052731 fluorine Chemical group 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 3
230000005494 condensation Effects 0.000 claims description 3
238000006698 hydrazinolysis reaction Methods 0.000 claims description 3
RNAODKZCUVVPEN-UHFFFAOYSA-N 1h-indol-2-ylmethanamine Chemical compound C1=CC=C2NC(CN)=CC2=C1 RNAODKZCUVVPEN-UHFFFAOYSA-N 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 11
125000001309 chloro group Chemical group Cl* 0.000 claims 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 8
125000001153 fluoro group Chemical group F* 0.000 claims 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims 1
239000002253 acid Substances 0.000 abstract description 12
150000003839 salts Chemical class 0.000 abstract description 11
239000002249 anxiolytic agent Substances 0.000 abstract description 4
230000000949 anxiolytic effect Effects 0.000 abstract description 3
229940005530 anxiolytics Drugs 0.000 abstract description 3
229940125723 sedative agent Drugs 0.000 abstract description 3
239000000932 sedative agent Substances 0.000 abstract description 3
125000000217 alkyl group Chemical group 0.000 abstract description 2
239000003326 hypnotic agent Substances 0.000 abstract description 2
230000000147 hypnotic effect Effects 0.000 abstract description 2
229940035363 muscle relaxants Drugs 0.000 abstract description 2
239000003158 myorelaxant agent Substances 0.000 abstract description 2
229940125681 anticonvulsant agent Drugs 0.000 abstract 1
239000001961 anticonvulsive agent Substances 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
239000000243 solution Substances 0.000 description 41
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
239000013078 crystal Substances 0.000 description 25
239000011541 reaction mixture Substances 0.000 description 22
238000002844 melting Methods 0.000 description 21
230000008018 melting Effects 0.000 description 21
229960001701 chloroform Drugs 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
239000000203 mixture Substances 0.000 description 16
239000011369 resultant mixture Substances 0.000 description 16
239000002904 solvent Substances 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
239000012044 organic layer Substances 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 12
239000000047 product Substances 0.000 description 12
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
241000699670 Mus sp. Species 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 10
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 9
238000001816 cooling Methods 0.000 description 9
239000000126 substance Substances 0.000 description 9
238000007792 addition Methods 0.000 description 8
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 8
JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
239000000725 suspension Substances 0.000 description 8
230000000694 effects Effects 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000006188 syrup Substances 0.000 description 7
235000020357 syrup Nutrition 0.000 description 7
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000008186 active pharmaceutical agent Substances 0.000 description 4
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
229960003529 diazepam Drugs 0.000 description 4
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 4
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000011282 treatment Methods 0.000 description 4
QRKJNCRCYBKANP-UHFFFAOYSA-N 2-amino-n-phenylacetamide Chemical compound NCC(=O)NC1=CC=CC=C1 QRKJNCRCYBKANP-UHFFFAOYSA-N 0.000 description 3
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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 3
AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
235000006408 oxalic acid Nutrition 0.000 description 3
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
RHZBRCQIKQUQHQ-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetyl chloride Chemical compound C1=CC=C2C(=O)N(CC(=O)Cl)C(=O)C2=C1 RHZBRCQIKQUQHQ-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
230000007059 acute toxicity Effects 0.000 description 2
231100000403 acute toxicity Toxicity 0.000 description 2
150000003931 anilides Chemical class 0.000 description 2
125000004181 carboxyalkyl group Chemical group 0.000 description 2
239000000969 carrier Substances 0.000 description 2
229960004782 chlordiazepoxide Drugs 0.000 description 2
ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000012213 gelatinous substance Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229960003975 potassium Drugs 0.000 description 2
235000007686 potassium Nutrition 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
229940093956 potassium carbonate Drugs 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
230000036647 reaction Effects 0.000 description 2
238000010825 rotarod performance test Methods 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
239000007858 starting material Substances 0.000 description 2
HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 1
KGLPWQKSKUVKMJ-UHFFFAOYSA-N 2,3-dihydrophthalazine-1,4-dione Chemical compound C1=CC=C2C(=O)NNC(=O)C2=C1 KGLPWQKSKUVKMJ-UHFFFAOYSA-N 0.000 description 1
FKASAVXZZLJTNX-UHFFFAOYSA-N 2-(dimethylamino)acetic acid;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(O)=O FKASAVXZZLJTNX-UHFFFAOYSA-N 0.000 description 1
XUXRXWLKUYPGMZ-UHFFFAOYSA-N 2-(tritylamino)acetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NCC(=O)O)C1=CC=CC=C1 XUXRXWLKUYPGMZ-UHFFFAOYSA-N 0.000 description 1
VFRCXEHNAFUTQC-UHFFFAOYSA-N 2-[[2-(phenylmethoxycarbonylamino)acetyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)CNC(=O)OCC1=CC=CC=C1 VFRCXEHNAFUTQC-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
ZYJMWXNUTNAPRF-UHFFFAOYSA-N 3,5-dichloro-2-phenyl-1h-indole Chemical compound N1C2=CC=C(Cl)C=C2C(Cl)=C1C1=CC=CC=C1 ZYJMWXNUTNAPRF-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
241000272496 Galliformes Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
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 1
239000003810 Jones reagent Substances 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical group [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
241001237728 Precis Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
MWFFOPCLIQFPII-UHFFFAOYSA-N [5-chloro-2-(methylamino)phenyl]-(2-chlorophenyl)methanol Chemical compound CNC1=CC=C(Cl)C=C1C(O)C1=CC=CC=C1Cl MWFFOPCLIQFPII-UHFFFAOYSA-N 0.000 description 1
DQYHYPVCQHTLRO-UHFFFAOYSA-N [5-chloro-2-(methylamino)phenyl]-(2-chlorophenyl)methanone Chemical compound CNC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl DQYHYPVCQHTLRO-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000006350 alkyl thio alkyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000004103 aminoalkyl group Chemical group 0.000 description 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000002082 anti-convulsion Effects 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
239000002585 base Substances 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
JHFQCKUKONOFIM-LJAQVGFWSA-N benzyl n-[(2s)-1-[(2-anilino-2-oxoethyl)amino]-3-[4-chloro-2-(2-chlorobenzoyl)phenyl]-1-oxopropan-2-yl]-n-methylcarbamate Chemical compound C([C@H](N(C)C(=O)OCC=1C=CC=CC=1)C(=O)NCC(=O)NC=1C=CC=CC=1)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl JHFQCKUKONOFIM-LJAQVGFWSA-N 0.000 description 1
IIFXYGSVEXILOC-UHFFFAOYSA-N benzyl n-[2-[[5-chloro-3-(2-chlorophenyl)-1-methylindol-2-yl]methylamino]-2-oxoethyl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(Cl)=CC=C2N(C)C=1CNC(=O)CNC(=O)OCC1=CC=CC=C1 IIFXYGSVEXILOC-UHFFFAOYSA-N 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
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005242 carbamoyl alkyl group Chemical group 0.000 description 1
108010051381 carbobenzoxyglycylglycine Proteins 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003179 convulsant agent Substances 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
238000003255 drug test Methods 0.000 description 1
230000003028 elevating effect Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
229940043257 glycylglycine Drugs 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
125000006289 hydroxybenzyl group Chemical group 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
125000006301 indolyl methyl group Chemical group 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000005358 mercaptoalkyl group Chemical group 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000004973 motor coordination Effects 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
239000006187 pill Substances 0.000 description 1
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000010998 test method Methods 0.000 description 1
GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
239000002023 wood Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA339,232A 1974-08-06 1979-11-06 Derives dipeptidiques et procede de production Expired CA1091652A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA339,232A CA1091652A (fr)	1974-08-06	1979-11-06	Derives dipeptidiques et procede de production

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
JP49090566A JPS605599B2 (ja)	1974-08-06	1974-08-06	アミノベンゾフエノン誘導体の製造法
JP905,566/74		1974-08-06
JP90565/1974		1974-08-06
JP49090565A JPS604199B2 (ja)	1974-08-06	1974-08-06	アニリン系ジペプチド誘導体の製造法
CA000232782A CA1181065A (fr)	1974-08-06	1975-07-31	Derives de dipeptide et methode de production
CA339,232A CA1091652A (fr)	1974-08-06	1979-11-06	Derives dipeptidiques et procede de production

Publications (1)

Publication Number	Publication Date
CA1091652A true CA1091652A (fr)	1980-12-16

Family

ID=27164062

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA339,232A Expired CA1091652A (fr)	1974-08-06	1979-11-06	Derives dipeptidiques et procede de production

Country Status (1)

Country	Link
CA (1)	CA1091652A (fr)

1979
- 1979-11-06 CA CA339,232A patent/CA1091652A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-12-16	MKEX	Expiry

Publication	Publication Date	Title
CA1331614C (fr)	1994-08-23	Derives acyl substitues d'acides 1,2,3,4-tetrahydroisoquinoline-3-carboxyliques
DE3789371T2 (de)	1994-09-08	Aryloxy- und Arylacyloxymethyl-Ketone als Thiolprotease-Hemmungsstoffe.
Roeske et al.	1956	Synthesis of a Protected Tetrapeptide Amide Containing the Carboxyl Terminal Sequence of Lysine-Vasopressin1
US4619916A (en)	1986-10-28	Tripeptide compounds containing pyroglutamic acid and tryptophan, process for their production and therapeutic applications
IE60128B1 (en)	1994-06-01	Hydroxylamine derivatives,their preparation and use as medicaments
RU2178419C2 (ru)	2002-01-20	Ингибиторы протеазы серина
JPH01157998A (ja)	1989-06-21	Ｌ−プロリン誘導体及びその製造方法並びにそれを含有する医薬組生物
KR910007575B1 (ko)	1991-09-28	N-알킬화된 디펩타이드 유도체의 제조방법
US4154727A (en)	1979-05-15	Dipeptide derivatives and their production
CA1091652A (fr)	1980-12-16	Derives dipeptidiques et procede de production
EP0103496A1 (fr)	1984-03-21	Dérivés aminés et iminés d'acides acylalkylamino-carbonyl substitués
EP0244836B1 (fr)	1993-08-18	Dérivés tripeptide
US4260601A (en)	1981-04-07	Chemical compounds
CN100374459C (zh)	2008-03-12	合成培哚普利及其药学可接受盐的新方法
US4240957A (en)	1980-12-23	Dipeptide derivatives and their production
EP0159396B1 (fr)	1990-06-27	Dérivés carboxyalkyl peptides
CA1249394A (fr)	1989-01-24	Composes pour le traitement de l'hypertension
CN100383160C (zh)	2008-04-23	合成培哚普利及其药学上可接受盐的新方法
CA1247085A (fr)	1988-12-20	Preparation de tripeptides renfermant la n-carboxyalcoylproline
CA1238902A (fr)	1988-07-05	Alkylamides de carboxyalkanoylpeptides
EP0001174A1 (fr)	1979-03-21	Un peptide et ses sels, procédés pour leur préparation et les compositions les contenant
EP1628956B1 (fr)	2010-11-17	Procede de preparation de composes ayant une action inhibitrice sur ace
US4505898A (en)	1985-03-19	Derivatives of acetylsalicylic acid and substituted phenylacetic acids and compositions containing them
US4452783A (en)	1984-06-05	Derivatives of substituted phenylacetic acids and compositions containing them
SU664560A3 (ru)	1979-05-25	Способ получени пептидов или их солей