CA1269666A - Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides - Google Patents

Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides

Info

Publication number: CA1269666A
Authority: CA; Canada
Prior art keywords: lower alkyl; hydrogen; carbonyl; proline; ester
Prior art date: 1982-07-22
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000566252A

Other languages

English (en)

Inventor

Sesha I. Natarajan

Eric M. Gordon

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.)

1982-07-22

Filing date

1988-05-06

Publication date

1990-05-29

1982-07-22 Priority claimed from US06/400,798 external-priority patent/US4623729A/en

1988-05-06 Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC

1988-05-06 Priority to CA000566252A priority Critical patent/CA1269666A/fr

1990-05-29 Application granted granted Critical

1990-05-29 Publication of CA1269666A publication Critical patent/CA1269666A/fr

2007-05-29 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 53
125000002924 primary amino group Chemical group [H]N([H])* 0.000 title description 29
239000002253 acid Substances 0.000 title description 26
125000001841 imino group Chemical group [H]N=* 0.000 title description 13
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 claims abstract description 6
125000000217 alkyl group Chemical group 0.000 claims description 78
239000001257 hydrogen Substances 0.000 claims description 64
229910052739 hydrogen Inorganic materials 0.000 claims description 64
-1 methoxy, methylthio Chemical group 0.000 claims description 61
239000000203 mixture Substances 0.000 claims description 42
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
125000001309 chloro group Chemical group Cl* 0.000 claims description 18
125000001153 fluoro group Chemical group F* 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000001246 bromo group Chemical group Br* 0.000 claims description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
125000005843 halogen group Chemical group 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
239000003937 drug carrier Substances 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 7
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 abstract description 6
102000004270 Peptidyl-Dipeptidase A Human genes 0.000 abstract description 6
108090000882 Peptidyl-Dipeptidase A Proteins 0.000 abstract description 6
239000002220 antihypertensive agent Substances 0.000 abstract description 4
230000005764 inhibitory process Effects 0.000 abstract description 4
102000003729 Neprilysin Human genes 0.000 abstract description 2
108090000028 Neprilysin Proteins 0.000 abstract description 2
239000000730 antalgic agent Substances 0.000 abstract description 2
238000002360 preparation method Methods 0.000 abstract description 2
229940035676 analgesics Drugs 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 93
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 77
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
229960002429 proline Drugs 0.000 description 53
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 50
150000002148 esters Chemical class 0.000 description 49
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
239000000047 product Substances 0.000 description 48
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
238000003756 stirring Methods 0.000 description 40
229940093499 ethyl acetate Drugs 0.000 description 36
235000019439 ethyl acetate Nutrition 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 32
239000000741 silica gel Substances 0.000 description 31
229910002027 silica gel Inorganic materials 0.000 description 31
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
150000002431 hydrogen Chemical group 0.000 description 28
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
229960001701 chloroform Drugs 0.000 description 22
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
239000012043 crude product Substances 0.000 description 21
150000003839 salts Chemical class 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 20
239000000243 solution Substances 0.000 description 19
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
239000003054 catalyst Substances 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
238000000034 method Methods 0.000 description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
229940086542 triethylamine Drugs 0.000 description 10
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
229960000443 hydrochloric acid Drugs 0.000 description 9
235000011167 hydrochloric acid Nutrition 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
230000007935 neutral effect Effects 0.000 description 8
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 8
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
159000000000 sodium salts Chemical class 0.000 description 7
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 7
SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 6
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
125000004185 ester group Chemical group 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
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
229940043230 sarcosine Drugs 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 5
JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 5
239000004471 Glycine Substances 0.000 description 5
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 5
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 5
LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
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 5
229910052736 halogen Inorganic materials 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
229910000343 potassium bisulfate Inorganic materials 0.000 description 5
239000000376 reactant Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 4
101800000734 Angiotensin-1 Proteins 0.000 description 4
102400000344 Angiotensin-1 Human genes 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
206010020772 Hypertension Diseases 0.000 description 4
229930194542 Keto Natural products 0.000 description 4
239000004472 Lysine Substances 0.000 description 4
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
108010077895 Sarcosine Proteins 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
229940099112 cornstarch Drugs 0.000 description 4
239000002934 diuretic Substances 0.000 description 4
125000001475 halogen functional group Chemical group 0.000 description 4
125000000468 ketone group Chemical group 0.000 description 4
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
235000013930 proline Nutrition 0.000 description 4
238000000746 purification Methods 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
WPBCXLCJWLNDPV-INIZCTEOSA-N (2s)-2-benzamido-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C1=CC=CC=C1 WPBCXLCJWLNDPV-INIZCTEOSA-N 0.000 description 3
125000005979 2-naphthyloxy group Chemical group 0.000 description 3
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 3
102000005862 Angiotensin II Human genes 0.000 description 3
101800000733 Angiotensin-2 Proteins 0.000 description 3
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-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
235000021355 Stearic acid Nutrition 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
229950006323 angiotensin ii Drugs 0.000 description 3
239000002585 base Substances 0.000 description 3
SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical compound Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
230000001882 diuretic effect Effects 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
241000894007 species Species 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
GKYAOKWOMSONDW-NRFANRHFSA-N (2s)-2-benzamido-3-(4-phenylmethoxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1OCC1=CC=CC=C1 GKYAOKWOMSONDW-NRFANRHFSA-N 0.000 description 2
NIOMUJJKCGJROX-UHFFFAOYSA-N 2-benzamidohexanoic acid Chemical compound CCCCC(C(O)=O)NC(=O)C1=CC=CC=C1 NIOMUJJKCGJROX-UHFFFAOYSA-N 0.000 description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 2
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238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229960001375 lactose Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
229960003739 methyclothiazide Drugs 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229960005483 polythiazide Drugs 0.000 description 1
229920000046 polythiazide Polymers 0.000 description 1
238000011176 pooling Methods 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
150000003147 proline derivatives Chemical class 0.000 description 1
150000003148 prolines Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000009491 slugging Methods 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 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
229960002256 spironolactone Drugs 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
229940032330 sulfuric acid Drugs 0.000 description 1
239000000725 suspension Substances 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
AGHANLSBXUWXTB-UHFFFAOYSA-N tienilic acid Chemical compound ClC1=C(Cl)C(OCC(=O)O)=CC=C1C(=O)C1=CC=CS1 AGHANLSBXUWXTB-UHFFFAOYSA-N 0.000 description 1
229960000356 tienilic acid Drugs 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
229960001288 triamterene Drugs 0.000 description 1
229960004813 trichlormethiazide Drugs 0.000 description 1
LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229960004799 tryptophan Drugs 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000566252A 1982-07-22 1988-05-06 Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides Expired - Fee Related CA1269666A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000566252A CA1269666A (fr)	1982-07-22	1988-05-06	Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US06/400,798 US4623729A (en)	1982-07-22	1982-07-22	Acylalkylaminocarbonyl substituted amino and imino acid compounds
US400,798		1982-07-22
CA 432963 CA1269666C (fr)	1982-07-22	1983-07-22	Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides
CA000566252A CA1269666A (fr)	1982-07-22	1988-05-06	Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides

Publications (1)

Publication Number	Publication Date
CA1269666A true CA1269666A (fr)	1990-05-29

Family

ID=25670105

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000566252A Expired - Fee Related CA1269666A (fr)	1982-07-22	1988-05-06	Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides

Country Status (1)

Country	Link
CA (1)	CA1269666A (fr)

1988
- 1988-05-06 CA CA000566252A patent/CA1269666A/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1995-11-29	MKLA	Lapsed

Publication	Publication Date	Title
CA1258948A (fr)	1989-08-29	Derives de substitution hydroxyles de peptides
EP0007477B1 (fr)	1982-04-28	Dérivés d'acides aminés substitués par 1-(3-mercapto-2-méthyl-propanoyl)prolyle et leurs sels, procédés pour les préparer et compositions pharmaceutiques les contenant
USH725H (en)	1990-01-02	Ureido amino and imino acids, compositions and methods for use
EP0052991B1 (fr)	1987-02-04	Composés de carboxyalkylaminoacides dérivés de prolines substituées diverses
EP0611375A1 (fr)	1994-08-24	Peptides inhibant la liberation d'il-1 beta
EP0331921A1 (fr)	1989-09-13	Inhibiteurs de la rénine, contenant des alpha-hétéroatome-acides aminés
HU181965B (en)	1983-11-28	Process for preparing new substituted proline derivatives
EP0037231A2 (fr)	1981-10-07	Dérivés acylés de l'acide octahydro-1H-indole-carboxylique-2
CA1245658A (fr)	1988-11-29	Derives de substitution acylalcoylaminocarbonyles d'amino- et d'imino-acides
US4382889A (en)	1983-05-10	Epoxysuccinic acid derivatives
PT86433B (pt)	1990-11-20	Processo para a preparacao de derivados de acidos tiol-carboxilicos
CA1261332A (fr)	1989-09-26	Derives de substitution esterifies d'aminoalcanoylureidoamino- et imino-acides et -esters
EP0159156A1 (fr)	1985-10-23	Uréidoamino- et -imino-acides hydroxy substitués
CA1269496A (fr)	1990-05-22	Mercaptocycloalcoylcarbonyl- et mercaptoarylcarbonyldipeptides
EP0158947B1 (fr)	1991-02-06	Dérivé de p-aminophénol ayant une activité mucrosecrétolytique fluide et antipyrétique, son procédé de préparation et ses compositions pharmaceutiques
PT86374B (pt)	1990-11-20	Processo para a preparacao de novos inibidores iii de renina e de composicoes farmaceuticas que os contem
US5221667A (en)	1993-06-22	Renin inhibiting peptides having an α-heteroatom amino acid at the P3 position
CA1295333C (fr)	1992-02-04	Composes acylaminoalcanoyles
US4734420A (en)	1988-03-29	Anti-hypertensive agents
JPH0526775B2 (fr)	1993-04-19
CA1285563C (fr)	1991-07-02	Amino et imino acides et esters d'ureidoalkanoylaminocarbonyl
KR890000769B1 (ko)	1989-04-05	프롤린 유도체의 제법
FR2487341A1 (fr)	1982-01-29	Tripeptides inhibiteurs de l'enzyme de transformation de l'angiotensine
CA2038379C (fr)	2002-11-05	Derives trifluoromethyle mercaptan et mercaptoacyle; methode d'utilisation
CA1253500A (fr)	1989-05-02	Urethanes ou thio-urethanes acylaminoalcanoyles