NL8006586A - N-adamanten-gesubstitueerde tetrapeptide-amiden. - Google Patents

N-adamanten-gesubstitueerde tetrapeptide-amiden. Download PDF

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Publication number: NL8006586A
Authority: NL; Netherlands
Prior art keywords: formula; methyl; solution; amino; hydrogen
Prior art date: 1979-12-03

Application number

NL8006586A

Other languages

English (en)

Dutch (nl)

Original Assignee

Searle & Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1979-12-03

Filing date

1980-12-03

Publication date

1981-07-01

1980-12-03 Application filed by Searle & Co filed Critical Searle & Co

1981-07-01 Publication of NL8006586A publication Critical patent/NL8006586A/nl

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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 82
150000001875 compounds Chemical class 0.000 claims description 45
-1 O-methylhosphosine Chemical compound 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 21
PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 15
150000002431 hydrogen Chemical group 0.000 claims description 13
229930182817 methionine Natural products 0.000 claims description 13
125000000539 amino acid group Chemical group 0.000 claims description 12
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 12
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 11
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 10
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 10
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 10
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 10
235000004279 alanine Nutrition 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
229910052736 halogen Chemical group 0.000 claims description 9
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 8
150000002367 halogens Chemical group 0.000 claims description 8
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 7
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 claims description 6
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 6
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
YWIQQKOKNPPGDO-VURMDHGXSA-N phenyldehydroalanine Chemical compound OC(=O)C(/N)=C/C1=CC=CC=C1 YWIQQKOKNPPGDO-VURMDHGXSA-N 0.000 claims description 6
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 9
QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 claims 8
QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 claims 8
125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims 7
LSNDLIKCFHLFKO-JTQLQIEISA-N (2s)-2-azaniumyl-3-(4-hydroxy-2,6-dimethylphenyl)propanoate Chemical compound CC1=CC(O)=CC(C)=C1C[C@H](N)C(O)=O LSNDLIKCFHLFKO-JTQLQIEISA-N 0.000 claims 4
GTVVZTAFGPQSPC-UHFFFAOYSA-N 4-nitrophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-UHFFFAOYSA-N 0.000 claims 4
AXDLCFOOGCNDST-SECBINFHSA-N (2r)-3-(4-hydroxyphenyl)-2-(methylazaniumyl)propanoate Chemical compound CN[C@@H](C(O)=O)CC1=CC=C(O)C=C1 AXDLCFOOGCNDST-SECBINFHSA-N 0.000 claims 2
SCIFESDRCALIIM-UHFFFAOYSA-N N-Me-Phenylalanine Natural products CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 claims 2
SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 claims 2
WJJGAKCAAJOICV-JTQLQIEISA-N (2s)-2-(dimethylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound CN(C)[C@H](C(O)=O)CC1=CC=C(O)C=C1 WJJGAKCAAJOICV-JTQLQIEISA-N 0.000 claims 1
KFHRMMHGGBCRIV-UHFFFAOYSA-N 2-azaniumyl-4-methoxybutanoate Chemical compound COCCC(N)C(O)=O KFHRMMHGGBCRIV-UHFFFAOYSA-N 0.000 claims 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 1
FLDDNEIHWWBOSO-DRJKYTIESA-N [(2S)-2-aminopropanoyl] 3-aminoadamantane-1-carboxylate Chemical compound N[C@@H](C)C(=O)OC(=O)C12CC3(CC(CC(C1)C3)C2)N FLDDNEIHWWBOSO-DRJKYTIESA-N 0.000 claims 1
APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 claims 1
239000000243 solution Substances 0.000 description 230
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 185
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 98
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 97
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
239000002904 solvent Substances 0.000 description 82
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 66
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 57
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 52
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
239000000047 product Substances 0.000 description 42
JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 37
238000000034 method Methods 0.000 description 37
229910000343 potassium bisulfate Inorganic materials 0.000 description 37
229940073584 methylene chloride Drugs 0.000 description 32
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
229910000041 hydrogen chloride Inorganic materials 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
239000000203 mixture Substances 0.000 description 29
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
229910052943 magnesium sulfate Inorganic materials 0.000 description 27
235000019341 magnesium sulphate Nutrition 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
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235000011152 sodium sulphate Nutrition 0.000 description 24
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 20
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
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YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
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239000010410 layer Substances 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
239000000741 silica gel Substances 0.000 description 14
229910002027 silica gel Inorganic materials 0.000 description 14
239000007787 solid Substances 0.000 description 14
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FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
150000008064 anhydrides Chemical class 0.000 description 11
235000015497 potassium bicarbonate Nutrition 0.000 description 11
229910000028 potassium bicarbonate Inorganic materials 0.000 description 11
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239000002244 precipitate Substances 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
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238000005406 washing Methods 0.000 description 10
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238000001816 cooling Methods 0.000 description 9
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229960005190 phenylalanine Drugs 0.000 description 9
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical group C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 8
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GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 5
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JAQUASYNZVUNQP-PVAVHDDUSA-N dextrorphan Chemical compound C1C2=CC=C(O)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 JAQUASYNZVUNQP-PVAVHDDUSA-N 0.000 description 1
229950006878 dextrorphan Drugs 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000002224 dissection Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical class OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 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
238000002474 experimental method Methods 0.000 description 1
239000012847 fine chemical Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
DALYXJVFSIYXMA-UHFFFAOYSA-N hydrogen sulfide dimer Chemical compound S.S DALYXJVFSIYXMA-UHFFFAOYSA-N 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960003406 levorphanol Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000155 melt Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229960005173 methiosulfonium chloride Drugs 0.000 description 1
SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
TVHCXXXXQNWQLP-DMTCNVIQSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound COC(=O)[C@@H](N)[C@@H](C)O TVHCXXXXQNWQLP-DMTCNVIQSA-N 0.000 description 1
LXGRNNZUKDXTIV-UHFFFAOYSA-N methyl 1-aminocyclopropane-1-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC(=O)C1(N)CC1 LXGRNNZUKDXTIV-UHFFFAOYSA-N 0.000 description 1
MCNJPKDIMSOGTM-SECBINFHSA-N methyl 2-[[(2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoyl]amino]acetate Chemical compound COC(=O)CNC(=O)[C@@H](CCSC)NC(=O)OC(C)(C)C MCNJPKDIMSOGTM-SECBINFHSA-N 0.000 description 1
SEGPJFKYVJYBFH-SCSAIBSYSA-N methyl 2-[[(2r)-2-aminopropanoyl]amino]acetate Chemical compound COC(=O)CNC(=O)[C@@H](C)N SEGPJFKYVJYBFH-SCSAIBSYSA-N 0.000 description 1
WULJQXTZWBDFSE-UHFFFAOYSA-N methyl 2-amino-3-(3-hydroxyphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)C(N)CC1=CC=CC(O)=C1 WULJQXTZWBDFSE-UHFFFAOYSA-N 0.000 description 1
BMCTUOOXHFSRDB-UHFFFAOYSA-N methyl 2-aminoadamantane-1-carboxylate Chemical compound C1C(C2)CC3CC2C(N)C1(C(=O)OC)C3 BMCTUOOXHFSRDB-UHFFFAOYSA-N 0.000 description 1
KDWBXERRHHGBST-UHFFFAOYSA-N methyl 2-aminoadamantane-1-carboxylate;hydrochloride Chemical compound Cl.C1C(C2)CC3CC2C(N)C1(C(=O)OC)C3 KDWBXERRHHGBST-UHFFFAOYSA-N 0.000 description 1
WIWRHVZLCWGIET-OTXHLKQPSA-N methyl 3-amino-2-[(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]adamantane-1-carboxylate Chemical compound C([C@@H](C(=O)C1C2(N)CC3CC(C2)CC1(C3)C(=O)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 WIWRHVZLCWGIET-OTXHLKQPSA-N 0.000 description 1
GMXYKQPNBFHSEJ-UHFFFAOYSA-N methyl 3-aminoadamantane-1-carboxylate;hydrochloride Chemical compound Cl.C1C(C2)CC3CC2(N)CC1(C(=O)OC)C3 GMXYKQPNBFHSEJ-UHFFFAOYSA-N 0.000 description 1
OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229940113083 morpholine Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
210000004197 pelvis Anatomy 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
KAQHZJVQFBJKCK-UHFFFAOYSA-L potassium pyrosulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OS([O-])(=O)=O KAQHZJVQFBJKCK-UHFFFAOYSA-L 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
229960002429 proline Drugs 0.000 description 1
NPSSWQJHYLDCNV-UHFFFAOYSA-N prop-2-enoic acid;hydrochloride Chemical compound Cl.OC(=O)C=C NPSSWQJHYLDCNV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
239000000523 sample Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007873 sieving Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
NQCHDDLNCFAKRO-JTFNFDHSSA-N tert-butyl n-[(2s)-1-[[(2r)-1-[[2-[[(2s)-1-(1-amino-2-adamantyl)-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)C1C2(N)CC3CC(C2)CC1C3)NC(=O)OC(C)(C)C)C1=CC=C(O)C=C1 NQCHDDLNCFAKRO-JTFNFDHSSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
238000001665 trituration Methods 0.000 description 1
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 1
238000005292 vacuum distillation Methods 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
239000002699 waste material Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Crystallography & Structural Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NL8006586A 1979-12-03 1980-12-03 N-adamanten-gesubstitueerde tetrapeptide-amiden. NL8006586A (nl)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US06/099,765 US4273704A (en)	1979-12-03	1979-12-03	N-Adamantane-substituted tetrapeptide amides
US9976579		1979-12-03

Publications (1)

Publication Number	Publication Date
NL8006586A true NL8006586A (nl)	1981-07-01

Family

ID=22276513

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8006586A NL8006586A (nl)	1979-12-03	1980-12-03	N-adamanten-gesubstitueerde tetrapeptide-amiden.

Country Status (16)

Country	Link
US (1)	US4273704A (da)
JP (1)	JPS5692847A (da)
AU (1)	AU6499080A (da)
BE (1)	BE886472A (da)
CA (1)	CA1151642A (da)
DE (1)	DE3044793A1 (da)
DK (1)	DK513480A (da)
ES (2)	ES8205753A1 (da)
FR (1)	FR2476073A1 (da)
GB (1)	GB2066262B (da)
IT (1)	IT1127930B (da)
NL (1)	NL8006586A (da)
NO (1)	NO803640L (da)
PT (1)	PT72141B (da)
SE (1)	SE8008428L (da)
ZA (1)	ZA807513B (da)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4404135A (en) *	1981-07-20	1983-09-13	G. D. Searle & Co.	Enkephalin derivatives
US4407746A (en) *	1981-12-14	1983-10-04	G. D. Searle & Co.	Cyclohexyl and phenyl substituted enkephalins
CS231221B1 (en) *	1982-06-29	1984-10-15	Martin Flegel	L-alanyl-d-isoglutamine adamantylamide
MX7527E (es) *	1983-08-16	1989-07-25	Univ Georgia Res Found	Procedimiento para la sintesis de un aminoacido de ciclopropilo
US4629784A (en) *	1983-08-16	1986-12-16	The University Of Georgia Research Foundation, Inc.	Synthesis of cyclopropane amino acids
US4510085A (en) *	1984-04-12	1985-04-09	G.D. Searle & Co.	Antihypertensive tetrapeptide amides
US4514332A (en) *	1984-04-16	1985-04-30	G. D. Searle & Co.	Tetrapeptide adamantyl amides
FR2572399B1 (fr) *	1984-10-31	1987-01-16	Panmedica Sa	Nouveaux derives de l'adamantanamine, leurs procedes de preparation et medicaments les contenant
US4880829A (en) *	1985-08-14	1989-11-14	G. D. Searle And Company	Substituted dipeptide amides #3
US4822775A (en) *	1986-02-14	1989-04-18	G. D. Searle & Co.	Phenyl substituted dipeptide amides
US4758675A (en) *	1986-07-14	1988-07-19	G. D. Searle & Co.	3-thiophene-substituted tyrosyl dipeptide amides
DE69130489T2 (de) *	1990-02-28	1999-05-12	Teikoku Seiyaku K.K., Kagawa	Physiologisch aktive Substanz die fähig ist Biomembran zu permeieren
US5652335A (en) *	1990-02-28	1997-07-29	Teikoku Seiyaku Kabushiki Kaisha	Physiologically active substance well capable of permeating biomembrane
EP1574495A1 (en)	1997-01-14	2005-09-14	Daicel Chemical Industries, Ltd.	Adamantane derivatives
US7795468B2 (en) *	2001-01-19	2010-09-14	Chevron U.S.A. Inc.	Functionalized higher diamondoids
US20050245534A1 (en) *	2004-04-29	2005-11-03	Link James T	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
US7880001B2 (en) *	2004-04-29	2011-02-01	Abbott Laboratories	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
US20100222316A1 (en) *	2004-04-29	2010-09-02	Abbott Laboratories	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
US20050261302A1 (en) *	2004-04-29	2005-11-24	Hoff Ethan D	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their therapeutic application
US8415354B2 (en) *	2004-04-29	2013-04-09	Abbott Laboratories	Methods of use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
EP1789380A1 (de) *	2004-07-23	2007-05-30	Justus-Liebig-Universität Giessen	Aminoadamantan-derivate, verfahren zu ihrer herstellung und ihre verwendung
US20090093463A1 (en) *	2004-11-02	2009-04-09	Agouron Pharmaceuticals Inc.	Novel compounds of substituted and unsubtituted adamantyl amides
MX2007008238A (es)	2005-01-05	2007-08-17	Abbott Lab	Derivados de adamantilo como inhibidores de la enzima 11-beta-hidroxiesteroide deshidrogenasa tipo 1.
US8198331B2 (en) *	2005-01-05	2012-06-12	Abbott Laboratories	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
US20090192198A1 (en)	2005-01-05	2009-07-30	Abbott Laboratories	Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme
HRP20050242B1 (en) *	2005-03-15	2010-09-30	Institut Ruđer Bošković	Synthetic peptides containing unnatural adamantane related amino acids for use as antitumour drugs
JP5736098B2 (ja) *	2007-08-21	2015-06-17	アッヴィ・インコーポレイテッド	中枢神経系障害を治療するための医薬組成物
EP2399926A1 (en) *	2010-06-22	2011-12-28	Justus-Liebig-Universität Giessen	Peptides incorporating 3-aminoadamantane carboxylic acids enhance synaptic plasticity and act as neurogenic agents
CN112552374B (zh) *	2019-09-10	2024-06-04	西藏海思科制药有限公司	一种肽酰胺类化合物及其中间体的制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK326477A (da) *	1976-07-27	1978-01-28	Reckitt & Colmann Prod Ltd	Kemiske forbindelser og fremgangsmade til fremstilling af samme

1979
- 1979-12-03 US US06/099,765 patent/US4273704A/en not_active Expired - Lifetime
1980
- 1980-11-28 DE DE19803044793 patent/DE3044793A1/de not_active Withdrawn
- 1980-12-02 AU AU64990/80A patent/AU6499080A/en not_active Withdrawn
- 1980-12-02 ES ES497353A patent/ES8205753A1/es not_active Expired
- 1980-12-02 SE SE8008428A patent/SE8008428L/ not_active Application Discontinuation
- 1980-12-02 CA CA000365903A patent/CA1151642A/en not_active Expired
- 1980-12-02 ZA ZA00807513A patent/ZA807513B/xx unknown
- 1980-12-02 DK DK513480A patent/DK513480A/da not_active Application Discontinuation
- 1980-12-02 NO NO803640A patent/NO803640L/no unknown
- 1980-12-02 IT IT50294/80A patent/IT1127930B/it active
- 1980-12-03 FR FR8025696A patent/FR2476073A1/fr not_active Withdrawn
- 1980-12-03 BE BE0/203025A patent/BE886472A/fr unknown
- 1980-12-03 GB GB8038684A patent/GB2066262B/en not_active Expired
- 1980-12-03 NL NL8006586A patent/NL8006586A/nl not_active Application Discontinuation
- 1980-12-03 JP JP17078580A patent/JPS5692847A/ja active Pending
- 1980-12-03 PT PT72141A patent/PT72141B/pt unknown
1981
- 1981-12-16 ES ES508060A patent/ES508060A0/es active Granted

Also Published As

Publication number	Publication date
ZA807513B (en)	1982-07-28
IT8050294A0 (it)	1980-12-02
BE886472A (fr)	1981-06-03
ES8300087A1 (es)	1982-10-01
GB2066262A (en)	1981-07-08
IT1127930B (it)	1986-05-28
ES497353A0 (es)	1982-06-16
US4273704A (en)	1981-06-16
PT72141B (en)	1981-10-28
GB2066262B (en)	1983-05-11
CA1151642A (en)	1983-08-09
ES8205753A1 (es)	1982-06-16
NO803640L (no)	1981-06-04
ES508060A0 (es)	1982-10-01
FR2476073A1 (fr)	1981-08-21
AU6499080A (en)	1981-06-11
JPS5692847A (en)	1981-07-27
PT72141A (en)	1981-01-01
DK513480A (da)	1981-07-09
DE3044793A1 (de)	1981-06-19
SE8008428L (sv)	1981-06-04

Legal Events

Date	Code	Title	Description
1984-08-01	BV	The patent application has lapsed

Publication	Publication Date	Title
NL8006586A (nl)	1981-07-01	N-adamanten-gesubstitueerde tetrapeptide-amiden.
Gacel et al.	1981	Evidence of the preferential involvement of. mu.-receptors in analgesia using enkephalins highly selective for peripheral. mu. or. delta. receptors
US4259234A (en)	1981-03-31	Analgesic compounds
EP0618223A2 (en)	1994-10-05	Peptides inhibiting interleukin 1-bêta release useful as antiinflammatory agents
US4472305A (en)	1984-09-18	Hexapeptide amides
GB1592552A (en)	1981-07-08	Pseudopeptides used as medicaments
US4304715A (en)	1981-12-08	Enkephalin analogues
US4540682A (en)	1985-09-10	Pharmaceutical peptides, preparation, use and intermediates
US4510082A (en)	1985-04-09	Pharmacologically active peptides
US4407746A (en)	1983-10-04	Cyclohexyl and phenyl substituted enkephalins
US4092304A (en)	1978-05-30	4-Substituted enkephalin derivatives
DD200799A5 (de)	1983-06-15	Verfahren zur herstellung von peptiden
EP0030847B1 (en)	1984-05-30	Pharmacologically active peptides, their preparation and pharmaceutical compositions containing them
US4265808A (en)	1981-05-05	Pharmacologically active peptides
US4322342A (en)	1982-03-30	Analgesic compounds
Pitzele et al.	1994	Enkephalin analogs as systemically active antinociceptive agents: O-and N-alkylated derivatives of the dipeptide amide L-2, 6-dimethyltyrosyl-N-(3-phenylpropyl)-D-alaninamide
GB1577115A (en)	1980-10-22	Container closure units
US4448717A (en)	1984-05-15	Pharmacologically active peptides
HU186375B (en)	1985-07-29	Process for the preparation of biologically active encephalina derivatives
CS199708B2 (en)	1980-07-31	Method of producing polypeptides and derivatives thereof having effect similar morphine
US4473497A (en)	1984-09-25	Pharmacologically active peptides
GB1587427A (en)	1981-04-01	Polypeptide derivatives
Okada et al.	1998	Amino acids and peptides. LII. Design and Synthesis of opioid mimetics containing a pyrazinone ring and examinaiton of their opioid receptor binding activity
US4247543A (en)	1981-01-27	Organic compounds
KR860001909B1 (ko)	1986-10-24	트리펩티드 유도체의 제조방법