PH26637A - Hydroxylamine hearing amino acid derivatives - Google Patents

Hydroxylamine hearing amino acid derivatives Download PDF

Info

Publication number: PH26637A
Authority: PH; Philippines
Prior art keywords: group; alkyl; butyl; isobutylsuccinyl; protected
Prior art date: 1986-03-11

Application number

PH34996A

Other languages

English (en)

Inventor

Balraj Krishan Handa

William Henry Johnson

Peter James Machin

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.)

1986-03-11

Filing date

1987-03-10

Publication date

1992-09-04

1986-03-11 Priority claimed from GB868605977A external-priority patent/GB8605977D0/en

1987-03-10 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1992-09-04 Publication of PH26637A publication Critical patent/PH26637A/en

Links

AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 title description 4
150000003862 amino acid derivatives Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 86
-1 p-hydroxymethyl Chemical group 0.000 claims description 77
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
238000000034 method Methods 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
229910052799 carbon Inorganic materials 0.000 claims description 14
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
230000002378 acidificating effect Effects 0.000 claims description 10
229940024606 amino acid Drugs 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
230000007062 hydrolysis Effects 0.000 claims description 8
238000006460 hydrolysis reaction Methods 0.000 claims description 8
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 7
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 6
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 6
229960003767 alanine Drugs 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000005101 aryl methoxy carbonyl group Chemical group 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
125000001495 ethyl group Chemical class [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 4
235000004279 alanine Nutrition 0.000 claims description 4
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
239000012876 carrier material Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 3
125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 3
239000004471 Glycine Substances 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
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 claims description 2
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 2
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims 1
PMKXAKKWRBOEIC-QMMMGPOBSA-N ethyl 2-[[(2s)-2-amino-4-methylpentanoyl]amino]acetate Chemical compound CCOC(=O)CNC(=O)[C@@H](N)CC(C)C PMKXAKKWRBOEIC-QMMMGPOBSA-N 0.000 claims 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
OZVLILWRDWSCNL-UHFFFAOYSA-N phthalic acid terephthalic acid Chemical compound C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C=1C(C(=O)O)=CC=CC1)(=O)O.C(C1=CC=C(C(=O)O)C=C1)(=O)O OZVLILWRDWSCNL-UHFFFAOYSA-N 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
239000000243 solution Substances 0.000 description 132
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 110
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
239000000203 mixture Substances 0.000 description 58
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 54
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
229960001701 chloroform Drugs 0.000 description 47
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
238000001704 evaporation Methods 0.000 description 36
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 35
230000008020 evaporation Effects 0.000 description 35
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
239000002904 solvent Substances 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
239000007787 solid Substances 0.000 description 25
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 21
235000019341 magnesium sulphate Nutrition 0.000 description 21
239000000706 filtrate Substances 0.000 description 20
238000010828 elution Methods 0.000 description 19
125000006239 protecting group Chemical group 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000006260 foam Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
238000004587 chromatography analysis Methods 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
239000002253 acid Substances 0.000 description 16
239000000047 product Substances 0.000 description 16
235000017557 sodium bicarbonate Nutrition 0.000 description 16
229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 15
150000002443 hydroxylamines Chemical class 0.000 description 14
229960003136 leucine Drugs 0.000 description 14
239000007858 starting material Substances 0.000 description 14
238000001914 filtration Methods 0.000 description 13
239000004395 L-leucine Substances 0.000 description 12
238000009833 condensation Methods 0.000 description 12
230000005494 condensation Effects 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
125000004494 ethyl ester group Chemical group 0.000 description 10
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 10
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 9
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000012043 crude product Substances 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
238000003776 cleavage reaction Methods 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 7
238000010992 reflux Methods 0.000 description 7
230000007017 scission Effects 0.000 description 7
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
238000007327 hydrogenolysis reaction Methods 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
239000000758 substrate Substances 0.000 description 5
NPIMKSLXCPUXPD-SECBINFHSA-N (2r)-4-methyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)CC(=O)OC(C)(C)C NPIMKSLXCPUXPD-SECBINFHSA-N 0.000 description 4
108060005980 Collagenase Proteins 0.000 description 4
102000029816 Collagenase Human genes 0.000 description 4
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
239000002775 capsule Substances 0.000 description 4
229960002424 collagenase Drugs 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
108090000765 processed proteins & peptides Proteins 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000001117 sulphuric acid Substances 0.000 description 4
235000011149 sulphuric acid Nutrition 0.000 description 4
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
ROBXZHNBBCHEIQ-BYPYZUCNSA-N ethyl (2s)-2-aminopropanoate Chemical compound CCOC(=O)[C@H](C)N ROBXZHNBBCHEIQ-BYPYZUCNSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
HHKUZUDKCCHXMN-GXTWGEPZSA-N (2r)-4-methyl-2-[(2s)-1-oxo-1-phenylmethoxypropan-2-yl]pentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)[C@H](C)C(=O)OCC1=CC=CC=C1 HHKUZUDKCCHXMN-GXTWGEPZSA-N 0.000 description 2
NZUBPFFSVXPWNB-GFCCVEGCSA-N (3r)-5-methyl-3-[(4-nitrophenyl)methoxycarbonyl]hexanoic acid Chemical compound CC(C)C[C@H](CC(O)=O)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 NZUBPFFSVXPWNB-GFCCVEGCSA-N 0.000 description 2
GMIDOMGRHSRKOX-GFCCVEGCSA-N (4-nitrophenyl)methyl (2r)-2-hydroxy-4-methylpentanoate Chemical compound CC(C)C[C@@H](O)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 GMIDOMGRHSRKOX-GFCCVEGCSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 2
NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 2
YJNQRRCNDSQTQO-ZDUSSCGKSA-N 2-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 YJNQRRCNDSQTQO-ZDUSSCGKSA-N 0.000 description 2
MCRZWYDXIGCFKO-UHFFFAOYSA-N 2-butylpropanedioic acid Chemical compound CCCCC(C(O)=O)C(O)=O MCRZWYDXIGCFKO-UHFFFAOYSA-N 0.000 description 2
ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 2
PUOHYWANBYYBMW-UHFFFAOYSA-N 4-bromo-azacyclotridecan-2-one Chemical compound BrC1CCCCCCCCCNC(=O)C1 PUOHYWANBYYBMW-UHFFFAOYSA-N 0.000 description 2
LYMTUUPKTSFKAQ-UHFFFAOYSA-N 4-methyl-2-[(phenylmethoxyamino)methyl]pentanoic acid Chemical compound CC(C)CC(C(O)=O)CNOCC1=CC=CC=C1 LYMTUUPKTSFKAQ-UHFFFAOYSA-N 0.000 description 2
PHCUMMALIDGEDQ-OAHLLOKOSA-N 4-o-tert-butyl 1-o-[(4-nitrophenyl)methyl] (2r)-2-(2-methylpropyl)butanedioate Chemical compound CC(C)(C)OC(=O)C[C@@H](CC(C)C)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 PHCUMMALIDGEDQ-OAHLLOKOSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
HBCKGPQEHPLNAU-UHFFFAOYSA-N Cl.NC1CCCCCCCCCNC(=O)C1 Chemical compound Cl.NC1CCCCCCCCCNC(=O)C1 HBCKGPQEHPLNAU-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
235000019759 Maize starch Nutrition 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
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238000002798 spectrophotometry method Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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 1
238000001665 trituration Methods 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
239000004474 valine Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 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
- C07K5/06086—Dipeptides with the first amino acid being basic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- 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
- 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
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
- 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
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
- 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
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- 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)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pain & Pain Management (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

PH34996A 1986-03-11 1987-03-10 Hydroxylamine hearing amino acid derivatives PH26637A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB868605977A GB8605977D0 (en)	1986-03-11	1986-03-11	Hydroxylamine derivatives
GB868629712A GB8629712D0 (en)	1986-03-11	1986-12-12	Hydroxylamine derivatives

Publications (1)

Publication Number	Publication Date
PH26637A true PH26637A (en)	1992-09-04

Family

ID=26290467

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH34996A PH26637A (en)	1986-03-11	1987-03-10	Hydroxylamine hearing amino acid derivatives

Country Status (11)

Country	Link
US (1)	US4996358A (da)
EP (1)	EP0236872B1 (da)
JP (1)	JPH0629228B2 (da)
AU (1)	AU588437B2 (da)
CA (1)	CA1314655C (da)
DE (1)	DE3782751D1 (da)
DK (1)	DK77487A (da)
IE (1)	IE60128B1 (da)
IL (1)	IL81790A0 (da)
NZ (1)	NZ219494A (da)
PH (1)	PH26637A (da)

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JPH08508027A (ja) *	1993-03-16	1996-08-27	ブリテッシュバイオテックファーマシューティカルズリミテッド	金属タンパク加水分解酵素阻害剤である天然アミノ酸誘導体
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CA2251292A1 (en) *	1996-04-12	1997-10-23	Bristol-Myers Squibb Company	N-formyl hydroxylamine containing compounds useful as ace inhibitors and/or nep inhibitors
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ATE226573T1 (de)	1996-08-28	2002-11-15	Procter & Gamble	Heterozyklische metalloproteaseinhibitoren
US6462023B1 (en)	1996-09-10	2002-10-08	British Biotech Pharmaceuticals, Ltd.	Cytostatic agents
US6953788B1 (en)	1996-09-19	2005-10-11	Aventis Pharmaceuticals Inc.	3-mercaptoacetylamino-1,5-substituted-2-oxo-azepan derivatives useful as inhibitors of matrix metalloproteinase
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US5985911A (en) *	1997-01-07	1999-11-16	Abbott Laboratories	C-terminal ketone inhibitors of matrix metalloproteinases and TNFα secretion
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US6696456B1 (en) *	1999-10-14	2004-02-24	The Procter & Gamble Company	Beta disubstituted metalloprotease inhibitors
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1987
- 1987-02-16 DK DK077487A patent/DK77487A/da not_active Application Discontinuation
- 1987-02-26 DE DE8787102771T patent/DE3782751D1/de not_active Expired - Fee Related
- 1987-02-26 EP EP87102771A patent/EP0236872B1/de not_active Expired - Lifetime
- 1987-03-03 CA CA000530988A patent/CA1314655C/en not_active Expired - Fee Related
- 1987-03-04 NZ NZ219494A patent/NZ219494A/xx unknown
- 1987-03-05 IL IL81790A patent/IL81790A0/xx not_active IP Right Cessation
- 1987-03-10 PH PH34996A patent/PH26637A/en unknown
- 1987-03-10 IE IE61087A patent/IE60128B1/en not_active IP Right Cessation
- 1987-03-11 JP JP62056412A patent/JPH0629228B2/ja not_active Expired - Lifetime
- 1987-03-11 AU AU69902/87A patent/AU588437B2/en not_active Ceased
1989
- 1989-04-11 US US07/336,264 patent/US4996358A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DE3782751D1 (de)	1993-01-07
DK77487A (da)	1987-09-12
AU6990287A (en)	1987-09-17
JPS62230757A (ja)	1987-10-09
NZ219494A (en)	1990-09-26
JPH0629228B2 (ja)	1994-04-20
AU588437B2 (en)	1989-09-14
US4996358A (en)	1991-02-26
IL81790A0 (en)	1987-10-20
DK77487D0 (da)	1987-02-16
CA1314655C (en)	1993-03-16
IE60128B1 (en)	1994-06-01
EP0236872A3 (en)	1989-09-13
IE870610L (en)	1987-09-11
EP0236872A2 (de)	1987-09-16
EP0236872B1 (de)	1992-11-25

Publication	Publication Date	Title
PH26637A (en)	1992-09-04	Hydroxylamine hearing amino acid derivatives
US5006651A (en)	1991-04-09	Phosphinic acid derivatives
EP0542525B1 (en)	1998-07-08	Antithrombotic agents
US4316889A (en)	1982-02-23	Novel peptidyl-arginine aldehyde derivatives and process for the preparation thereof
AU772024B2 (en)	2004-04-08	Inhibitors of urokinase and blood vessel formation
GB2085444A (en)	1982-04-28	Novel Anticoagulant agmatine derivatives and process for the preparation thereof
US5252566A (en)	1993-10-12	Antithrombotic agents
US5416093A (en)	1995-05-16	Antithrombotic agents
JPH02264795A (ja)	1990-10-29	グリシン誘導体
HU209413B (en)	1994-05-30	Method for producing 2-azabicyclo [3.1.0] hexane-3-carboxylic acid derivatives as well as their physiologically acceptable salts
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