JPS60136554A - エンケフアリナ−ゼ抑制剤 - Google Patents

エンケフアリナ−ゼ抑制剤

Info

Publication number: JPS60136554A
Authority: JP; Japan
Prior art keywords: hydrogen; acid; lower alkyl; compound according; carbon atoms
Prior art date: 1983-10-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Granted

Application number

JP59206961A

Other languages

English (en)

Japanese (ja)

Other versions

JPH0430950B2 (fr

Inventor

ノーマ・ジー・デラニー

エリック・エム・ゴードン

ミゲル・エイ・オンデッテイ

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

ER Squibb and Sons LLC

Original Assignee

ER Squibb and Sons LLC

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.)

1983-10-03

Filing date

1984-10-01

Publication date

1985-07-20

1984-10-01 Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC

1985-07-20 Publication of JPS60136554A publication Critical patent/JPS60136554A/ja

1992-05-25 Publication of JPH0430950B2 publication Critical patent/JPH0430950B2/ja

Status Granted legal-status Critical Current

Links

229940122586 Enkephalinase inhibitor Drugs 0.000 title description 2
239000002792 enkephalinase inhibitor Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 49
-1 hydroxy-methoxy Chemical group 0.000 claims description 46
125000000217 alkyl group Chemical group 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
125000004432 carbon atom Chemical group C* 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 16
150000002431 hydrogen Chemical class 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 8
238000000034 method Methods 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 3
241001465754 Metazoa Species 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
239000000932 sedative agent Substances 0.000 claims description 2
230000001624 sedative effect Effects 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
239000000203 mixture Substances 0.000 description 80
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
239000000243 solution Substances 0.000 description 55
239000007787 solid Substances 0.000 description 50
239000002253 acid Substances 0.000 description 43
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
238000003756 stirring Methods 0.000 description 36
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
238000002844 melting Methods 0.000 description 30
230000008018 melting Effects 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
238000002360 preparation method Methods 0.000 description 28
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 20
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
239000000284 extract Substances 0.000 description 17
238000004519 manufacturing process Methods 0.000 description 17
229910052938 sodium sulfate Inorganic materials 0.000 description 17
235000011152 sodium sulphate Nutrition 0.000 description 17
150000004702 methyl esters Chemical class 0.000 description 16
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
150000001412 amines Chemical class 0.000 description 14
239000012267 brine Substances 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
102000003729 Neprilysin Human genes 0.000 description 11
108090000028 Neprilysin Proteins 0.000 description 11
239000012141 concentrate Substances 0.000 description 11
235000008504 concentrate Nutrition 0.000 description 11
239000010410 layer Substances 0.000 description 11
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
238000000921 elemental analysis Methods 0.000 description 10
229910000343 potassium bisulfate Inorganic materials 0.000 description 10
239000012299 nitrogen atmosphere Substances 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
125000004356 hydroxy functional group Chemical group O* 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
HNBDRPTVWVGKBR-UHFFFAOYSA-N methyl pentanoate Chemical compound CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 8
UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000007788 liquid Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000000463 material Substances 0.000 description 6
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 6
XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
SFKTYEXKZXBQRQ-UHFFFAOYSA-J thorium(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Th+4] SFKTYEXKZXBQRQ-UHFFFAOYSA-J 0.000 description 6
238000005917 acylation reaction Methods 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
OZECFIJVSAYAPH-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;chloride Chemical compound Cl.CCN(C(C)C)C(C)C OZECFIJVSAYAPH-UHFFFAOYSA-N 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
235000008206 alpha-amino acids Nutrition 0.000 description 4
230000000202 analgesic effect Effects 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
229940099112 cornstarch Drugs 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
238000005245 sintering Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 3
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229910052770 Uranium Inorganic materials 0.000 description 3
230000010933 acylation Effects 0.000 description 3
150000001371 alpha-amino acids Chemical class 0.000 description 3
OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
235000013355 food flavoring agent Nutrition 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000002609 medium Substances 0.000 description 3
FAKIZCQRTPAOSH-UHFFFAOYSA-N methyl 5-aminopentanoate;hydrochloride Chemical compound Cl.COC(=O)CCCCN FAKIZCQRTPAOSH-UHFFFAOYSA-N 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
102000004196 processed proteins & peptides Human genes 0.000 description 3
150000003467 sulfuric acid derivatives Chemical class 0.000 description 3
WPGPRLVPWACBHW-UHFFFAOYSA-N (4-methoxy-4-oxobutyl)azanium;chloride Chemical compound Cl.COC(=O)CCCN WPGPRLVPWACBHW-UHFFFAOYSA-N 0.000 description 2
BCAAXVOKLXDSPD-UHFFFAOYSA-N 2-(acetylsulfanylmethyl)-3-phenylpropanoic acid Chemical compound CC(=O)SCC(C(O)=O)CC1=CC=CC=C1 BCAAXVOKLXDSPD-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 2
239000005541 ACE inhibitor Substances 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
XNCNNDVCAUWAIT-UHFFFAOYSA-N Methyl heptanoate Chemical compound CCCCCCC(=O)OC XNCNNDVCAUWAIT-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
239000006286 aqueous extract Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
235000019658 bitter taste Nutrition 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000010828 elution Methods 0.000 description 2
229960003750 ethyl chloride Drugs 0.000 description 2
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
DNMCSEZPFDMEHC-UHFFFAOYSA-N methyl 8-aminooctanoate;hydrochloride Chemical compound Cl.COC(=O)CCCCCCCN DNMCSEZPFDMEHC-UHFFFAOYSA-N 0.000 description 2
NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 2
JGHZJRVDZXSNKQ-UHFFFAOYSA-N methyl octanoate Chemical compound CCCCCCCC(=O)OC JGHZJRVDZXSNKQ-UHFFFAOYSA-N 0.000 description 2
XPQPWPZFBULGKT-UHFFFAOYSA-N methyl undecanoate Chemical compound CCCCCCCCCCC(=O)OC XPQPWPZFBULGKT-UHFFFAOYSA-N 0.000 description 2
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
235000019260 propionic acid Nutrition 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
150000003242 quaternary ammonium salts Chemical class 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
HEMRQGJQHXIYOI-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.OC(=O)C1=CC=CC=C1O HEMRQGJQHXIYOI-UHFFFAOYSA-N 0.000 description 1
RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 1
ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
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Landscapes

Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Furan Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)

JP59206961A 1983-10-03 1984-10-01 エンケフアリナ−ゼ抑制剤 Granted JPS60136554A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
US538731		1983-10-03
US64122184A	1984-08-16	1984-08-16
US641221		1984-08-16

Publications (2)

Publication Number	Publication Date
JPS60136554A true JPS60136554A (ja)	1985-07-20
JPH0430950B2 JPH0430950B2 (fr)	1992-05-25

Family

ID=24571462

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP59206961A Granted JPS60136554A (ja)	1983-10-03	1984-10-01	エンケフアリナ−ゼ抑制剤

Country Status (1)

Country	Link
JP (1)	JPS60136554A (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6431757A (en) *	1987-07-17	1989-02-02	Roi Moogan Rii	Method and compound for decreasing skin inflammation
JPH06102648B2 (ja) *	1990-05-17	1994-12-14	シェリング・コーポレーション	メルカプトアシルアミノ酸のジスルフィド誘導体
JPH07593B2 (ja) *	1989-04-10	1995-01-11	シェリング・コーポレーション	メルカプト―アシルアミノ酸

1984
- 1984-10-01 JP JP59206961A patent/JPS60136554A/ja active Granted

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6431757A (en) *	1987-07-17	1989-02-02	Roi Moogan Rii	Method and compound for decreasing skin inflammation
JPH07593B2 (ja) *	1989-04-10	1995-01-11	シェリング・コーポレーション	メルカプト―アシルアミノ酸
JPH06102648B2 (ja) *	1990-05-17	1994-12-14	シェリング・コーポレーション	メルカプトアシルアミノ酸のジスルフィド誘導体

Also Published As

Publication number	Publication date
JPH0430950B2 (fr)	1992-05-25

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JPS60136554A - エンケフアリナ−ゼ抑制剤 - Google Patents

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