DD243932A5 - Verfahren zur herstellung von n,n'-dialkylguanidino-dipeptiden - Google Patents

Verfahren zur herstellung von n,n'-dialkylguanidino-dipeptiden Download PDF

Info

Publication number: DD243932A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; radicals; proline; group; dipeptide
Prior art date: 1985-03-22

Application number

DD86288166A

Other languages

German (de)

English (en)

Inventor

John J Nestor

Original Assignee

��@��Kk��

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.)

1985-03-22

Filing date

1986-03-21

Publication date

1987-03-18

1986-03-21 Application filed by ��@��Kk�� filed Critical ��@��Kk��

1987-03-18 Publication of DD243932A5 publication Critical patent/DD243932A5/de

Links

229910052757 nitrogen Inorganic materials 0.000 title claims description 41
238000004519 manufacturing process Methods 0.000 title description 2
108010016626 Dipeptides Proteins 0.000 claims abstract description 70
238000000034 method Methods 0.000 claims abstract description 65
238000002360 preparation method Methods 0.000 claims abstract description 28
230000008569 process Effects 0.000 claims abstract description 28
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 21
150000003147 proline derivatives Chemical class 0.000 claims abstract description 19
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 17
150000001875 compounds Chemical class 0.000 claims description 118
-1 sulphonyloxy group Chemical group 0.000 claims description 73
150000003839 salts Chemical class 0.000 claims description 71
239000002253 acid Substances 0.000 claims description 49
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
125000000217 alkyl group Chemical group 0.000 claims description 24
239000002168 alkylating agent Substances 0.000 claims description 24
229940100198 alkylating agent Drugs 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 23
230000029936 alkylation Effects 0.000 claims description 23
238000005804 alkylation reaction Methods 0.000 claims description 23
239000002585 base Substances 0.000 claims description 23
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 22
238000009833 condensation Methods 0.000 claims description 18
230000005494 condensation Effects 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
230000007062 hydrolysis Effects 0.000 claims description 16
238000006460 hydrolysis reaction Methods 0.000 claims description 16
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
150000003862 amino acid derivatives Chemical class 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
230000002829 reductive effect Effects 0.000 claims description 13
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
229910052794 bromium Inorganic materials 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
235000019445 benzyl alcohol Nutrition 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
238000007327 hydrogenolysis reaction Methods 0.000 claims description 10
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230000002152 alkylating effect Effects 0.000 claims description 9
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
150000003973 alkyl amines Chemical class 0.000 claims description 7
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238000005886 esterification reaction Methods 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
239000011630 iodine Substances 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
231100000252 nontoxic Toxicity 0.000 claims description 7
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
230000009467 reduction Effects 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
230000032050 esterification Effects 0.000 claims description 6
125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
230000003000 nontoxic effect Effects 0.000 claims description 6
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
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QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
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239000002262 Schiff base Substances 0.000 claims description 3
150000004753 Schiff bases Chemical class 0.000 claims description 3
230000010933 acylation Effects 0.000 claims description 3
238000005917 acylation reaction Methods 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical group 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 2
125000000539 amino acid group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
238000006894 reductive elimination reaction Methods 0.000 claims 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 claims 2
125000004122 cyclic group Chemical group 0.000 claims 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 abstract description 10
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238000006243 chemical reaction Methods 0.000 description 48
230000015572 biosynthetic process Effects 0.000 description 30
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
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150000003254 radicals Chemical class 0.000 description 18
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
150000001408 amides Chemical class 0.000 description 11
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235000019441 ethanol Nutrition 0.000 description 9
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QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
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HLCHESOMJVGDSJ-LOYHVIPDSA-N (3r)-n-[(2r)-3-(4-chlorophenyl)-1-[4-cyclohexyl-4-(1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-1-oxopropan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide Chemical compound C1=CC(Cl)=CC=C1C[C@H](C(=O)N1CCC(CN2N=CN=C2)(CC1)C1CCCCC1)NC(=O)[C@@H]1NCC2=CC=CC=C2C1 HLCHESOMJVGDSJ-LOYHVIPDSA-N 0.000 description 6
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JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
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FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
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 5
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ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
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BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 4
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125000001589 carboacyl group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
101150062912 cct3 gene Proteins 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
229960002155 chlorothiazide Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000005352 clarification Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000007859 condensation product Substances 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
150000001470 diamides Chemical class 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
229960003199 etacrynic acid Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
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 description 1
229960003883 furosemide Drugs 0.000 description 1
229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229940028332 halog Drugs 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
108010025306 histidylleucine Proteins 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
QNRXNRGSOJZINA-UHFFFAOYSA-N indoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CC2=C1 QNRXNRGSOJZINA-UHFFFAOYSA-N 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
238000009533 lab test Methods 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 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
230000003211 malignant effect Effects 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
229940097258 other antihypertensives in atc Drugs 0.000 description 1
229940097271 other diuretics in atc Drugs 0.000 description 1
230000001151 other effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
239000006179 pH buffering agent Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000004526 pharmaceutical effect Effects 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920006122 polyamide resin Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000010970 precious metal Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
125000001308 pyruvoyl group Chemical group O=C([*])C(=O)C([H])([H])[H] 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000008299 semisolid dosage form Substances 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
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
229940035044 sorbitan monolaurate Drugs 0.000 description 1
241000894007 species Species 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
VVKCNYOQHJEXRB-UHFFFAOYSA-N tert-butyl chloro carbonate Chemical compound CC(C)(C)OC(=O)OCl VVKCNYOQHJEXRB-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
229960004605 timolol Drugs 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
229940117013 triethanolamine oleate Drugs 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960004418 trolamine Drugs 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/14—Angiotensins: Related peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
- 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
- A61P9/12—Antihypertensives
- 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)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Biochemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Genetics & Genomics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pyrrole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

DD86288166A 1985-03-22 1986-03-21 Verfahren zur herstellung von n,n'-dialkylguanidino-dipeptiden DD243932A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US71476785A	1985-03-22	1985-03-22

Publications (1)

Publication Number	Publication Date
DD243932A5 true DD243932A5 (de)	1987-03-18

Family

ID=24871369

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD86288166A DD243932A5 (de)	1985-03-22	1986-03-21	Verfahren zur herstellung von n,n'-dialkylguanidino-dipeptiden

Country Status (15)

Country	Link
EP (1)	EP0196841A1 (da)
JP (1)	JPS61227594A (da)
KR (1)	KR860007287A (da)
CN (1)	CN86101850A (da)
AU (1)	AU5502386A (da)
DD (1)	DD243932A5 (da)
DK (1)	DK133686A (da)
ES (2)	ES8801930A1 (da)
FI (1)	FI861210A7 (da)
GR (1)	GR860755B (da)
HU (1)	HUT40143A (da)
IL (1)	IL78219A0 (da)
NO (1)	NO861141L (da)
PT (1)	PT82250B (da)
ZA (1)	ZA862139B (da)

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US5231080A (en) *	1985-10-15	1993-07-27	Hoechst Aktiengesellschaft	Method for the treatment of atherosclerosis, thrombosis, and peripheral vessel disease
US5231084A (en) *	1986-03-27	1993-07-27	Hoechst Aktiengesellschaft	Compounds having a cognition adjuvant action, agents containing them, and the use thereof for the treatment and prophylaxis of cognitive dysfuncitons
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ATE70048T1 (de) *	1986-09-10	1991-12-15	Syntex Inc	Selektive amidinierung von diaminen.
US4876359A (en) *	1986-10-07	1989-10-24	Ss Pharmaceutical Co., Ltd.	Novel gamma-butyrolactone derivatives
DE3803225A1 (de) *	1988-02-04	1989-08-17	Hoechst Ag	Aminosaeureamide mit psychotroper wirkung, verfahren zu ihrer herstellung, sie enthaltende mittel und deren verwendung
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US5318992A (en) *	1990-02-26	1994-06-07	Merrell Dow Pharmaceuticals Inc.	Inhibitors of nitric oxide biosynthesis
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US5543423A (en) *	1994-11-16	1996-08-06	Vertex Pharmaceuticals, Incorporated	Amino acid derivatives with improved multi-drug resistance activity
US7056935B2 (en)	1995-06-07	2006-06-06	Gpi Nil Holdings, Inc.	Rotamase enzyme activity inhibitors
US5859031A (en) *	1995-06-07	1999-01-12	Gpi Nil Holdings, Inc.	Small molecule inhibitors of rotamase enzyme activity
US5801197A (en) *	1995-10-31	1998-09-01	Gpi Nil Holdings, Inc.	Rotamase enzyme activity inhibitors
US5786378A (en) *	1996-09-25	1998-07-28	Gpi Nil Holdings, Inc.	Heterocyclic thioesters
US5801187A (en)	1996-09-25	1998-09-01	Gpi-Nil Holdings, Inc.	Heterocyclic esters and amides
US6218424B1 (en)	1996-09-25	2001-04-17	Gpi Nil Holdings, Inc.	Heterocyclic ketone and thioester compounds and uses
US5846979A (en)	1997-02-28	1998-12-08	Gpi Nil Holdings, Inc.	N-oxides of heterocyclic esters, amides, thioesters, and ketones
US6187796B1 (en)	1998-06-03	2001-02-13	Gpi Nil Holdings, Inc.	Sulfone hair growth compositions and uses
US6274602B1 (en)	1998-06-03	2001-08-14	Gpi Nil Holdings, Inc.	Heterocyclic thioester and ketone hair growth compositions and uses
US20010049381A1 (en)	1997-06-04	2001-12-06	Gpl Nil Holdings, Inc.,	Pyrrolidine derivative hair growth compositions and uses
US6187784B1 (en)	1998-06-03	2001-02-13	Gpi Nil Holdings, Inc.	Pipecolic acid derivative hair growth compositions and uses
US6271244B1 (en)	1998-06-03	2001-08-07	Gpi Nil Holdings, Inc.	N-linked urea or carbamate of heterocyclic thioester hair growth compositions and uses
US5945441A (en)	1997-06-04	1999-08-31	Gpi Nil Holdings, Inc.	Pyrrolidine carboxylate hair revitalizing agents
US6172087B1 (en)	1998-06-03	2001-01-09	Gpi Nil Holding, Inc.	N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US6429215B1 (en)	1998-06-03	2002-08-06	Gpi Nil Holdings, Inc.	N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
WO1999062487A1 (en)	1998-06-03	1999-12-09	Gpi Nil Holdings, Inc.	Heterocyclic ester and amide hair growth compositions and uses
US6331537B1 (en)	1998-06-03	2001-12-18	Gpi Nil Holdings, Inc.	Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
US6335348B1 (en)	1998-08-14	2002-01-01	Gpi Nil Holdings, Inc.	Nitrogen-containing linear and azepinyl/ compositions and uses for vision and memory disorders
US6218423B1 (en)	1998-08-14	2001-04-17	Gpi Nil Holdings, Inc.	Pyrrolidine derivatives for vision and memory disorders
US6395758B1 (en)	1998-08-14	2002-05-28	Gpi Nil Holdings, Inc.	Small molecule carbamates or ureas for vision and memory disorders
US6339101B1 (en)	1998-08-14	2002-01-15	Gpi Nil Holdings, Inc.	N-linked sulfonamides of N-heterocyclic carboxylic acids or isosteres for vision and memory disorders
US7338976B1 (en)	1998-08-14	2008-03-04	Gpi Nil Holdings, Inc.	Heterocyclic esters or amides for vision and memory disorders
US6376517B1 (en)	1998-08-14	2002-04-23	Gpi Nil Holdings, Inc.	Pipecolic acid derivatives for vision and memory disorders
US6337340B1 (en)	1998-08-14	2002-01-08	Gpi Nil Holdings, Inc.	Carboxylic acids and isosteres of heterocyclic ring compounds having multiple heteroatoms for vision and memory disorders
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1986
- 1986-03-19 CN CN198686101850A patent/CN86101850A/zh active Pending
- 1986-03-20 JP JP61064660A patent/JPS61227594A/ja active Pending
- 1986-03-21 GR GR860755A patent/GR860755B/el unknown
- 1986-03-21 HU HU861192A patent/HUT40143A/hu unknown
- 1986-03-21 ES ES553266A patent/ES8801930A1/es not_active Expired
- 1986-03-21 EP EP86302111A patent/EP0196841A1/en not_active Withdrawn
- 1986-03-21 IL IL78219A patent/IL78219A0/xx unknown
- 1986-03-21 FI FI861210A patent/FI861210A7/fi not_active IP Right Cessation
- 1986-03-21 AU AU55023/86A patent/AU5502386A/en not_active Abandoned
- 1986-03-21 DD DD86288166A patent/DD243932A5/de unknown
- 1986-03-21 DK DK133686A patent/DK133686A/da not_active Application Discontinuation
- 1986-03-21 NO NO861141A patent/NO861141L/no unknown
- 1986-03-21 ZA ZA862139A patent/ZA862139B/xx unknown
- 1986-03-21 PT PT82250A patent/PT82250B/pt unknown
- 1986-03-22 KR KR1019860002141A patent/KR860007287A/ko not_active Ceased
1988
- 1988-03-30 ES ES557827A patent/ES8900017A1/es not_active Expired

Also Published As

Publication number	Publication date
NO861141L (no)	1986-09-23
GR860755B (en)	1986-05-27
ES553266A0 (es)	1988-03-16
ZA862139B (en)	1987-11-25
PT82250A (en)	1986-04-01
PT82250B (en)	1988-01-07
IL78219A0 (en)	1986-07-31
KR860007287A (ko)	1986-10-10
FI861210A0 (fi)	1986-03-21
EP0196841A1 (en)	1986-10-08
AU5502386A (en)	1986-09-25
CN86101850A (zh)	1987-02-04
JPS61227594A (ja)	1986-10-09
ES557827A0 (es)	1988-11-16
HUT40143A (en)	1986-11-28
ES8900017A1 (es)	1988-11-16
DK133686D0 (da)	1986-03-21
ES8801930A1 (es)	1988-03-16
DK133686A (da)	1986-09-23
FI861210A7 (fi)	1986-09-23

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