PH26575A - Peptide derivatives and pharmaceutical composition containing said compound - Google Patents

Peptide derivatives and pharmaceutical composition containing said compound Download PDF

Info

Publication number: PH26575A
Authority: PH; Philippines
Prior art keywords: carbons; group; product; aryl; methyl
Prior art date: 1985-01-22

Application number

PH33310A

Other languages

English (en)

Inventor

Scott Haven Bergeson

John Antony Schwartz

Donald John Wolanin

Philip Duke Edwards

Richard Alan Wildonger

Andrew Shaw

Mark Morris Stein

Diane Amy Trainor

Original Assignee

Ici America Inc

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.)

1985-01-22

Filing date

1990-04-27

Publication date

1992-08-19

1985-01-22 Priority claimed from GB858501522A external-priority patent/GB8501522D0/en

1985-01-22 Priority claimed from GB858501523A external-priority patent/GB8501523D0/en

1985-01-22 Priority claimed from GB858501524A external-priority patent/GB8501524D0/en

1990-04-27 Application filed by Ici America Inc filed Critical Ici America Inc

1992-08-19 Publication of PH26575A publication Critical patent/PH26575A/en

Links

150000001875 compounds Chemical class 0.000 title claims description 127
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
108090000765 processed proteins & peptides Proteins 0.000 title description 12
-1 c¢hleoro Chemical group 0.000 claims description 209
125000003118 aryl group Chemical group 0.000 claims description 152
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 126
125000000217 alkyl group Chemical group 0.000 claims description 120
229910052757 nitrogen Inorganic materials 0.000 claims description 73
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
229910052799 carbon Inorganic materials 0.000 claims description 44
125000003710 aryl alkyl group Chemical group 0.000 claims description 41
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 41
125000003545 alkoxy group Chemical group 0.000 claims description 40
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 35
125000001153 fluoro group Chemical group F* 0.000 claims description 33
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
239000002253 acid Substances 0.000 claims description 23
125000004104 aryloxy group Chemical group 0.000 claims description 20
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
125000005842 heteroatom Chemical group 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 19
239000001301 oxygen Substances 0.000 claims description 19
125000000753 cycloalkyl group Chemical group 0.000 claims description 17
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000001589 carboacyl group Chemical group 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
125000003368 amide group Chemical group 0.000 claims description 10
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 10
125000004429 atom Chemical group 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 9
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 7
125000000068 chlorophenyl group Chemical group 0.000 claims description 7
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
125000005281 alkyl ureido group Chemical group 0.000 claims description 6
125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 claims description 6
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 6
125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 6
125000005421 aryl sulfonamido group Chemical group 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 5
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 5
125000005333 aroyloxy group Chemical group 0.000 claims description 5
239000002585 base Substances 0.000 claims description 5
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
150000001408 amides Chemical class 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 claims 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
239000001530 fumaric acid Substances 0.000 claims 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
239000011976 maleic acid Substances 0.000 claims 1
231100000252 nontoxic Toxicity 0.000 claims 1
230000003000 nontoxic effect Effects 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 706
239000000047 product Substances 0.000 description 420
238000000034 method Methods 0.000 description 266
239000000243 solution Substances 0.000 description 199
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 194
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 193
238000003818 flash chromatography Methods 0.000 description 129
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 127
238000004128 high performance liquid chromatography Methods 0.000 description 110
239000000203 mixture Substances 0.000 description 105
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 101
238000000746 purification Methods 0.000 description 98
239000000463 material Substances 0.000 description 96
235000019439 ethyl acetate Nutrition 0.000 description 95
239000011541 reaction mixture Substances 0.000 description 84
239000000741 silica gel Substances 0.000 description 83
229910002027 silica gel Inorganic materials 0.000 description 83
229960001866 silicon dioxide Drugs 0.000 description 83
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 82
238000006243 chemical reaction Methods 0.000 description 79
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
238000004458 analytical method Methods 0.000 description 78
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 77
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 76
239000012267 brine Substances 0.000 description 71
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 71
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
229910002091 carbon monoxide Inorganic materials 0.000 description 68
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 66
239000012043 crude product Substances 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 50
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
239000007787 solid Substances 0.000 description 47
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 42
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 39
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 39
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 37
239000002904 solvent Substances 0.000 description 34
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 31
VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
238000007792 addition Methods 0.000 description 29
239000000706 filtrate Substances 0.000 description 29
239000000499 gel Substances 0.000 description 25
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 23
238000004587 chromatography analysis Methods 0.000 description 23
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
125000001931 aliphatic group Chemical group 0.000 description 22
239000006260 foam Substances 0.000 description 22
239000012044 organic layer Substances 0.000 description 22
125000000623 heterocyclic group Chemical group 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 19
239000010410 layer Substances 0.000 description 19
102100033174 Neutrophil elastase Human genes 0.000 description 18
238000010828 elution Methods 0.000 description 18
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 17
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
238000003756 stirring Methods 0.000 description 17
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
239000000843 powder Substances 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
239000011734 sodium Substances 0.000 description 15
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 14
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 13
125000006615 aromatic heterocyclic group Chemical group 0.000 description 13
125000004356 hydroxy functional group Chemical group O* 0.000 description 13
239000000725 suspension Substances 0.000 description 13
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
241000755710 Eilica Species 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
125000005097 aminocarbonylalkyl group Chemical group 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 12
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 11
239000003480 eluent Substances 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 10
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 10
238000000926 separation method Methods 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 9
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 9
239000003112 inhibitor Substances 0.000 description 9
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 9
239000003921 oil Substances 0.000 description 9
238000012746 preparative thin layer chromatography Methods 0.000 description 9
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000003902 lesion Effects 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 8
229910052717 sulfur Inorganic materials 0.000 description 8
239000011593 sulfur Substances 0.000 description 8
235000001508 sulfur Nutrition 0.000 description 8
229960005349 sulfur Drugs 0.000 description 8
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
229960000549 4-dimethylaminophenol Drugs 0.000 description 7
229910019093 NaOCl Inorganic materials 0.000 description 7
125000003342 alkenyl group Chemical group 0.000 description 7
125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 description 7
239000000872 buffer Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical class ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
125000004658 aryl carbonyl amino group Chemical group 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
239000013078 crystal Substances 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 6
125000001624 naphthyl group Chemical group 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
206010014561 Emphysema Diseases 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000003806 alkyl carbonyl amino group Chemical group 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
238000010171 animal model Methods 0.000 description 5
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 5
125000005129 aryl carbonyl group Chemical group 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
238000004821 distillation Methods 0.000 description 5
238000001035 drying Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
210000004072 lung Anatomy 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 5
239000000758 substrate Substances 0.000 description 5
239000006188 syrup Substances 0.000 description 5
235000020357 syrup Nutrition 0.000 description 5
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
238000009835 boiling Methods 0.000 description 4
125000004799 bromophenyl group Chemical group 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 4
239000011651 chromium Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000008263 liquid aerosol Substances 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
230000008569 process Effects 0.000 description 4
208000005333 pulmonary edema Diseases 0.000 description 4
230000006340 racemization Effects 0.000 description 4
238000010992 reflux Methods 0.000 description 4
239000004576 sand Substances 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
JXGVXCZADZNAMJ-NSHDSACASA-N (2s)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 JXGVXCZADZNAMJ-NSHDSACASA-N 0.000 description 3
NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 3
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 3
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150000004679 hydroxides Chemical class 0.000 description 1
208000006278 hypochromic anemia Diseases 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
230000000415 inactivating effect Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
239000001282 iso-butane Chemical class 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
BYULKSYWZLCXAG-UHFFFAOYSA-N isocyanato benzoate Chemical compound O=C=NOC(=O)C1=CC=CC=C1 BYULKSYWZLCXAG-UHFFFAOYSA-N 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
229950003188 isovaleryl diethylamide Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical class OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
KDXZREBVGAGZHS-UHFFFAOYSA-M methohexital sodium Chemical compound [Na+].CCC#CC(C)C1(CC=C)C(=O)N=C([O-])N(C)C1=O KDXZREBVGAGZHS-UHFFFAOYSA-M 0.000 description 1
HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
WVYBBOXJKXXXOY-UHFFFAOYSA-N methyl 12-hydroxydodecanoate Chemical compound COC(=O)CCCCCCCCCCCO WVYBBOXJKXXXOY-UHFFFAOYSA-N 0.000 description 1
CSTFJAKYMFPIJV-UHFFFAOYSA-N methyl 2-(4-carbamoylphenoxy)acetate Chemical compound COC(=O)COC1=CC=C(C(N)=O)C=C1 CSTFJAKYMFPIJV-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
VBWFYEFYHJRJER-UHFFFAOYSA-N methyl 4-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=C(CO)C=C1 VBWFYEFYHJRJER-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 1
DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
238000000643 oven drying Methods 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
238000005897 peptide coupling reaction Methods 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
230000002688 persistence Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
QIIPQYDSKRYMFG-UHFFFAOYSA-N phenyl hydrogen carbonate Chemical class OC(=O)OC1=CC=CC=C1 QIIPQYDSKRYMFG-UHFFFAOYSA-N 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 1
239000012453 solvate Substances 0.000 description 1
LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
210000003802 sputum Anatomy 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
238000012546 transfer Methods 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
238000001323 two-dimensional chromatography Methods 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
238000000108 ultra-filtration Methods 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
150000003673 urethanes Chemical class 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
- C07C205/02—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
- C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- 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
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- 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
- C07K5/08—Tripeptides
- C07K5/0819—Tripeptides with the first amino acid being acidic
- 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
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- 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)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pulmonology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

PH33310A 1985-01-22 1990-04-27 Peptide derivatives and pharmaceutical composition containing said compound PH26575A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB858501522A GB8501522D0 (en)	1985-01-22	1985-01-22	Dipeptide derivatives
GB858501523A GB8501523D0 (en)	1985-01-22	1985-01-22	Tripeptide derivatives
GB858501524A GB8501524D0 (en)	1985-01-22	1985-01-22	Tetrapeptide derivatives

Publications (1)

Publication Number	Publication Date
PH26575A true PH26575A (en)	1992-08-19

Family

ID=27262565

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH33310A PH26575A (en)	1985-01-22	1990-04-27	Peptide derivatives and pharmaceutical composition containing said compound

Country Status (25)

Country	Link
US (2)	US4910190A (el)
EP (1)	EP0189305B1 (el)
JP (2)	JPH0759591B2 (el)
KR (1)	KR910002689B1 (el)
CN (1)	CN1027640C (el)
AU (1)	AU594658B2 (el)
CA (1)	CA1341023C (el)
CZ (1)	CZ278063B6 (el)
DE (1)	DE3686172T2 (el)
DK (1)	DK172736B1 (el)
ES (3)	ES8706169A1 (el)
FI (1)	FI84171C (el)
GB (1)	GB8600263D0 (el)
GR (1)	GR860169B (el)
HK (1)	HK18097A (el)
HU (1)	HU206370B (el)
IE (1)	IE58957B1 (el)
IL (1)	IL77680A (el)
NO (1)	NO169493C (el)
PH (1)	PH26575A (el)
PL (1)	PL150268B1 (el)
PT (1)	PT81887B (el)
SK (1)	SK278095B6 (el)
UA (1)	UA39093C2 (el)
ZW (1)	ZW1486A1 (el)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8600263D0 (en) *	1985-01-22	1986-02-12	Ici America Inc	Peptide derivatives
US5055450A (en) *	1985-01-22	1991-10-08	Ici Americas Inc.	Peptide derivatives
IL77748A (en) *	1985-02-04	1991-11-21	Merrell Dow Pharma	Amino acid and peptide derivatives as peptidase inhibitors
US5496927A (en) *	1985-02-04	1996-03-05	Merrell Pharmaceuticals Inc.	Peptidase inhibitors
ATE71934T1 (de) *	1985-06-07	1992-02-15	Ici America Inc	Selektionierte difluorverbindungen.
EP0276101A3 (en) *	1987-01-19	1989-11-23	Ici Americas Inc.	Substituted peptide derivatives
GB8809316D0 (en) *	1987-05-11	1988-05-25	Ici America Inc	Heterocyclic ketones
US5182263A (en) *	1988-04-25	1993-01-26	Hoffmann-La Roche Inc.	Analogs of tyrosine sulfate or tyrosine phosphate containing peptides
US5296608A (en) *	1988-04-25	1994-03-22	Hoffman-La Roche Inc.	Intermediates for analogs of tyrosine sulfate or tyrosine phosphate containing peptides
IL90872A0 (en) *	1988-07-08	1990-02-09	Smithkline Beckman Corp	Retroviral protease binding peptides
EP0369391A3 (en) *	1988-11-15	1991-09-25	Boehringer Ingelheim Pharmaceuticals Inc.	N-substituted amides
GB8910547D0 (en) *	1989-05-08	1989-06-21	Ici America Inc	Substituted ketones
GB8910550D0 (en) *	1989-05-08	1989-06-21	Ici America Inc	Substituted amides
US5221665A (en) *	1989-10-27	1993-06-22	Boehringer Ingelheim Pharmaceuticals, Inc.	N-substituted amides
DE69129083T2 (de) *	1990-05-24	1998-07-09	Zeneca Ltd	Therapeutisches Mittel zur Vorbeugung und Behandlung des Atemnotsyndroms bei Erwachsenen
DE69131058T2 (de) *	1990-05-24	1999-09-09	Zeneca Ltd.	Verwendung einer therapeutischen Zusammensetzung zur Behandlung von Bronchitis
US5162348A (en) *	1990-05-24	1992-11-10	Imperial Chemical Industries Plc	Treatment of cystic fibrosis
GB9014132D0 (en) *	1990-06-25	1990-08-15	Ici Plc	Agent for therapy
US5296591A (en) *	1990-12-31	1994-03-22	Fujisawa Pharmaceutical Co., Ltd.	Trifluoromethylketone derivatives, processes for preparation thereof and use thereof
GB9207145D0 (en) *	1991-04-18	1992-05-13	Ici Plc	Heterocyclic amides
US5521179A (en) *	1991-04-18	1996-05-28	Zeneca Limited	Heterocyclic amides
US5340801A (en) *	1991-05-08	1994-08-23	Rhone-Poulenc Rorer Pharmaceuticals Inc.	Compounds having cholecystokinin and gastrin antagonistic properties
AU655301B2 (en) *	1991-05-23	1994-12-15	Merrell Pharmaceuticals Inc.	Inhibitors of cathepsin G and elastase for preventing connective tissue degradation
GB9113164D0 (en) *	1991-06-18	1991-08-07	Ici Plc	Pharmaceutical agent
AU2390892A (en) *	1991-08-08	1993-03-02	Yamanouchi Pharmaceutical Co., Ltd.	Urea derivative
AU658426B2 (en) *	1991-08-15	1995-04-13	Zeneca Limited	Substituted heterocycles
GB9216272D0 (en) *	1991-08-15	1992-09-09	Ici Plc	Substituted heterocycles
US5714470A (en) *	1991-08-22	1998-02-03	Merrell Pharmaceuticals, Inc.	Orally-active elastase inhibitors
US5478811A (en) *	1991-08-22	1995-12-26	Merrell Dow Pharmaceuticals Inc.	Orally-active elastase inhibitors
CA2133657A1 (en) *	1992-04-16	1993-10-28	Peter R. Bernstein	Substituted derivatives
US5486529A (en) *	1992-04-16	1996-01-23	Zeneca Limited	Certain pyridyl ketones for treating diseases involving leukocyte elastase
GB9211783D0 (en) *	1992-06-04	1992-07-15	Ici Plc	Amide derivatives
GB9214053D0 (en) *	1992-07-02	1992-08-12	Ici Plc	Heterocyclic amides
FR2694295B1 (fr) *	1992-07-28	1994-09-02	Adir	Nouveaux peptides dérivés de trifluoromethylcetones, leur procéde de préparation et les compositions pharmaceutiques qui les contiennent.
US5780590A (en) *	1993-10-15	1998-07-14	Rhone-Poulenc Rorer Pharmaceuticals Inc.	Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
GB9402680D0 (en) *	1994-02-11	1994-04-06	Zeneca Ltd	Pyrrolidine derivatives
FR2719589B1 (fr) *	1994-05-05	1996-06-14	Adir	Nouveaux peptides dérivés de trifluorométhylcétones, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
AU696292B2 (en) *	1994-06-02	1998-09-03	Merrell Pharmaceuticals Inc.	Acylated enol derivatives as prodrugs of elastase inhibitors
DE69513167T2 (de) *	1994-06-02	2000-06-15	Merrell Pharmaceuticals Inc., Cincinnati	Perfluoroalkyll ketone, inhibitoren von elastase und prozess zur deren herstellung
CA2189527C (en) *	1994-06-02	2000-12-19	William A. Metz, Jr.	Novel elastase inhibitors
US6693072B2 (en) *	1994-06-02	2004-02-17	Aventis Pharmaceuticals Inc.	Elastase inhibitors
GB9502152D0 (en) *	1995-02-03	1995-03-29	Zeneca Ltd	Proline derivatives
US5948886A (en) *	1996-11-20	1999-09-07	Hoechst Marion Roussel, Inc.	Acylated enol derivatives of α-ketoesters and α-ketoamides
US6172044B1 (en)	1995-12-01	2001-01-09	Aventis Pharmaceuticals Inc.	Acylated enol derivative of α-ketoesters and α-ketoamides
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1986
- 1986-01-07 GB GB868600263A patent/GB8600263D0/en active Pending
- 1986-01-20 EP EP86300379A patent/EP0189305B1/en not_active Expired - Lifetime
- 1986-01-20 DE DE8686300379T patent/DE3686172T2/de not_active Expired - Fee Related
- 1986-01-20 SK SK395-86A patent/SK278095B6/sk unknown
- 1986-01-20 CZ CS86395A patent/CZ278063B6/cs not_active IP Right Cessation
- 1986-01-21 PL PL1986257573A patent/PL150268B1/pl unknown
- 1986-01-21 FI FI860281A patent/FI84171C/fi not_active IP Right Cessation
- 1986-01-21 DK DK198600308A patent/DK172736B1/da not_active IP Right Cessation
- 1986-01-21 IE IE18086A patent/IE58957B1/en not_active IP Right Cessation
- 1986-01-21 ZW ZW14/86A patent/ZW1486A1/xx unknown
- 1986-01-21 GR GR860169A patent/GR860169B/el not_active IP Right Cessation
- 1986-01-21 UA UA4024099A patent/UA39093C2/uk unknown
- 1986-01-21 NO NO860190A patent/NO169493C/no not_active IP Right Cessation
- 1986-01-21 HU HU86276A patent/HU206370B/hu not_active IP Right Cessation
- 1986-01-22 ES ES551113A patent/ES8706169A1/es not_active Expired
- 1986-01-22 JP JP61010328A patent/JPH0759591B2/ja not_active Expired - Fee Related
- 1986-01-22 IL IL77680A patent/IL77680A/xx not_active IP Right Cessation
- 1986-01-22 CA CA000500144A patent/CA1341023C/en not_active Expired - Fee Related
- 1986-01-22 AU AU52623/86A patent/AU594658B2/en not_active Ceased
- 1986-01-22 KR KR1019860000375A patent/KR910002689B1/ko not_active IP Right Cessation
- 1986-01-22 CN CN86101066A patent/CN1027640C/zh not_active Expired - Lifetime
- 1986-01-22 PT PT81887A patent/PT81887B/pt not_active IP Right Cessation
- 1986-09-01 ES ES557048A patent/ES8707551A1/es not_active Expired
1987
- 1987-01-20 US US07/005,538 patent/US4910190A/en not_active Expired - Lifetime
- 1987-01-30 ES ES557363A patent/ES8802526A1/es not_active Expired
1990
- 1990-04-27 PH PH33310A patent/PH26575A/en unknown
1992
- 1992-08-06 JP JP4210009A patent/JPH0680039B2/ja not_active Expired - Fee Related
1995
- 1995-06-06 US US08/467,333 patent/US5726158A/en not_active Expired - Fee Related
1997
- 1997-02-13 HK HK18097A patent/HK18097A/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
KR910002689B1 (ko)	1991-05-03
AU5262386A (en)	1986-07-31
FI860281A0 (fi)	1986-01-21
GB8600263D0 (en)	1986-02-12
NO169493C (no)	1992-07-01
NO860190L (no)	1986-07-23
US4910190A (en)	1990-03-20
UA39093C2 (uk)	2001-06-15
PL150268B1 (en)	1990-05-31
ES557363A0 (es)	1988-07-01
FI84171B (fi)	1991-07-15
ES8706169A1 (es)	1987-05-16
US5726158A (en)	1998-03-10
EP0189305A2 (en)	1986-07-30
DK30886A (da)	1986-07-23
IE860180L (en)	1986-07-22
IL77680A (en)	1990-12-23
DK30886D0 (da)	1986-01-21
CA1341023C (en)	2000-06-13
SK278095B6 (en)	1995-12-06
CN1027640C (zh)	1995-02-15
ZW1486A1 (en)	1987-09-30
HU206370B (en)	1992-10-28
GR860169B (en)	1986-05-15
IE58957B1 (en)	1993-12-01
NO169493B (no)	1992-03-23
DE3686172T2 (de)	1993-01-14
FI84171C (fi)	1991-10-25
HK18097A (en)	1997-02-13
CS39586A3 (en)	1992-01-15
FI860281A (fi)	1986-07-23
ES557048A0 (es)	1987-08-01
ES8707551A1 (es)	1987-08-01
AU594658B2 (en)	1990-03-15
KR860005835A (ko)	1986-08-13
CZ278063B6 (en)	1993-08-11
PL257573A1 (en)	1987-03-23
DE3686172D1 (de)	1992-09-03
JPS61218518A (ja)	1986-09-29
PT81887B (pt)	1988-05-27
EP0189305B1 (en)	1992-07-29
HUT39464A (en)	1986-09-29
EP0189305A3 (en)	1988-10-05
ES551113A0 (es)	1987-05-16
DK172736B1 (da)	1999-06-21
JPH0680039B2 (ja)	1994-10-12
JPH0759591B2 (ja)	1995-06-28
ES8802526A1 (es)	1988-07-01
CN86101066A (zh)	1986-11-05
PT81887A (en)	1986-02-01
JPH05246984A (ja)	1993-09-24

Publication	Publication Date	Title
PH26575A (en)	1992-08-19	Peptide derivatives and pharmaceutical composition containing said compound
US5055450A (en)	1991-10-08	Peptide derivatives
US4880780A (en)	1989-11-14	Selected difluoro derivatives
JP2529825B2 (ja)	1996-09-04	新規なペプチダ−ゼ阻害剤
CA2189526C (en)	2001-02-27	Perfluoroalkyl ketone inhibitors of elastase and processes for making the same
US5907068A (en)	1999-05-25	Peptide derivatives
AU689589B2 (en)	1998-04-02	Novel elastase inhibitors
EP0276101A2 (en)	1988-07-27	Substituted peptide derivatives
US5714470A (en)	1998-02-03	Orally-active elastase inhibitors
EP0762887B1 (en)	2001-09-26	Acylated enol derivatives as prodrugs of elastase inhibitors
AU622315B2 (en)	1992-04-02	Peptide derivatives
AU595326B2 (en)	1990-03-29	Difluoro peptide compounds
MXPA96006030A (en)	1998-10-23	Novedous elast inhibitors
MXPA96006031A (en)	1998-10-23	Inhibitors of elastase perfluoroalquilic cetone and processes to manufacture
IL125429A (en)	2001-07-24	Perfluoroalkyl ketone inhibitors of elastase, processes for making the same and pharmaceutical compositions containing them