CS232000B2 - Manufacturing process of new ergoline derovatives - Google Patents

Manufacturing process of new ergoline derovatives Download PDF

Info

Publication number: CS232000B2
Authority: CS; Czechoslovakia
Prior art keywords: group; methyl; ergoline; carbon atoms; yield
Prior art date: 1981-11-06

Application number

CS827752A

Other languages

Czech (cs)

English (en)

Other versions

CS775282A2 (en

Inventor

Luigi Bernardi

Aldemio Temperilli

Daniela Ruggieri

Giuliana Arcari

Patricia Salvati

Original Assignee

Erba Farmitalia

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.)

1981-11-06

Filing date

1982-11-01

Publication date

1985-01-16

1982-11-01 Application filed by Erba Farmitalia filed Critical Erba Farmitalia

1984-01-16 Publication of CS775282A2 publication Critical patent/CS775282A2/cs

1985-01-16 Publication of CS232000B2 publication Critical patent/CS232000B2/cs

Links

AWFDCTXCTHGORH-HGHGUNKESA-N 6-[4-[(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carbonyl]piperazin-1-yl]-1-methylpyridin-2-one Chemical compound O=C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)N(CC1)CCN1C1=CC=CC(=O)N1C AWFDCTXCTHGORH-HGHGUNKESA-N 0.000 title claims abstract description 68
238000004519 manufacturing process Methods 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 42
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
150000003839 salts Chemical class 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 3
125000004414 alkyl thio group Chemical group 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 44
125000004432 carbon atom Chemical group C* 0.000 claims description 11
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
239000012948 isocyanate Substances 0.000 claims description 4
150000002513 isocyanates Chemical class 0.000 claims description 4
150000002540 isothiocyanates Chemical class 0.000 claims description 4
125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
238000009835 boiling Methods 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
239000002904 solvent Substances 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
229910052799 carbon Inorganic materials 0.000 claims 1
230000003276 anti-hypertensive effect Effects 0.000 abstract description 2
125000001183 hydrocarbyl group Chemical group 0.000 abstract 2
125000003118 aryl group Chemical group 0.000 abstract 1
125000004104 aryloxy group Chemical group 0.000 abstract 1
125000000623 heterocyclic group Chemical group 0.000 abstract 1
-1 3-benzoyl-thioureidomethyl Chemical group 0.000 description 28
CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 14
241000700159 Rattus Species 0.000 description 13
RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
VITFJKNVGRZRKB-UHFFFAOYSA-N acetyl isothiocyanate Chemical compound CC(=O)N=C=S VITFJKNVGRZRKB-UHFFFAOYSA-N 0.000 description 5
CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 5
229960002474 hydralazine Drugs 0.000 description 5
230000001262 anti-secretory effect Effects 0.000 description 4
230000035488 systolic blood pressure Effects 0.000 description 4
238000005303 weighing Methods 0.000 description 4
241001465754 Metazoa Species 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
OCKPROYBCPQWJO-UHFFFAOYSA-N acetyl isocyanate Chemical compound CC(=O)N=C=O OCKPROYBCPQWJO-UHFFFAOYSA-N 0.000 description 3
230000001078 anti-cholinergic effect Effects 0.000 description 3
230000000026 anti-ulcerogenic effect Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000002496 gastric effect Effects 0.000 description 3
238000002203 pretreatment Methods 0.000 description 3
101100231508 Caenorhabditis elegans ceh-5 gene Proteins 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 description 2
MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 description 2
230000036772 blood pressure Effects 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
BNTOYYSKEDTQHC-QFIXIFRTSA-N n-[[(6ar,9r,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]methylcarbamoyl]benzamide Chemical compound C([C@@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C)NC(=O)NC(=O)C1=CC=CC=C1 BNTOYYSKEDTQHC-QFIXIFRTSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
230000028327 secretion Effects 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
SJVGFKBLUYAEOK-SFHVURJKSA-N 6-[4-[(3S)-3-(3,5-difluorophenyl)-3,4-dihydropyrazole-2-carbonyl]piperidin-1-yl]pyrimidine-4-carbonitrile Chemical compound FC=1C=C(C=C(C=1)F)[C@@H]1CC=NN1C(=O)C1CCN(CC1)C1=CC(=NC=N1)C#N SJVGFKBLUYAEOK-SFHVURJKSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
229930003347 Atropine Natural products 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241001340534 Eido Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
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 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
IPCRBOOJBPETMF-UHFFFAOYSA-N N-acetylthiourea Chemical compound CC(=O)NC(N)=S IPCRBOOJBPETMF-UHFFFAOYSA-N 0.000 description 1
QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 description 1
206010030201 Oesophageal ulcer Diseases 0.000 description 1
RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
208000007107 Stomach Ulcer Diseases 0.000 description 1
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 1
229930006000 Sucrose Natural products 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
IXCCQSTVBSTCLP-PSOPSSQASA-N [(6ar,9s,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]methanamine Chemical compound C1=CC([C@H]2C[C@@H](CN)CN([C@@H]2C2)C)=C3C2=CNC3=C1 IXCCQSTVBSTCLP-PSOPSSQASA-N 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000002253 acid Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
230000000767 anti-ulcer Effects 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
229960000396 atropine Drugs 0.000 description 1
UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
230000037396 body weight Effects 0.000 description 1
208000006218 bradycardia Diseases 0.000 description 1
230000036471 bradycardia Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000002183 duodenal effect Effects 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
230000027119 gastric acid secretion Effects 0.000 description 1
210000004051 gastric juice Anatomy 0.000 description 1
210000001156 gastric mucosa Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000007774 longterm Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000000203 mixture Substances 0.000 description 1
BNZBMEIFAOYZEA-UHFFFAOYSA-N n-cyanoacetamide Chemical compound CC(=O)NC#N BNZBMEIFAOYZEA-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000001301 oxygen Chemical group 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
230000001175 peptic effect Effects 0.000 description 1
235000020004 porter Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
LYULLJDMUFOQHU-UHFFFAOYSA-N propanoyl isothiocyanate Chemical compound CCC(=O)N=C=S LYULLJDMUFOQHU-UHFFFAOYSA-N 0.000 description 1
230000035485 pulse pressure Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000010992 reflux Methods 0.000 description 1
102000012498 secondary active transmembrane transporter activity proteins Human genes 0.000 description 1
108040003878 secondary active transmembrane transporter activity proteins Proteins 0.000 description 1
238000004062 sedimentation Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000003826 tablet Substances 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
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/10—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hetero atoms directly attached in position 8
- C07D457/12—Nitrogen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CS827752A 1981-11-06 1982-11-01 Manufacturing process of new ergoline derovatives CS232000B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB8133631		1981-11-06

Publications (2)

Publication Number	Publication Date
CS775282A2 CS775282A2 (en)	1984-01-16
CS232000B2 true CS232000B2 (en)	1985-01-16

Family

ID=10525712

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS827752A CS232000B2 (en)	1981-11-06	1982-11-01	Manufacturing process of new ergoline derovatives

Country Status (21)

Country	Link
US (1)	US4500712A (sv)
JP (1)	JPS5885886A (sv)
AT (1)	AT381091B (sv)
AU (1)	AU553903B2 (sv)
BE (1)	BE894927A (sv)
CA (1)	CA1191841A (sv)
CH (1)	CH650506A5 (sv)
CS (1)	CS232000B2 (sv)
DE (1)	DE3240727A1 (sv)
DK (1)	DK494882A (sv)
FI (1)	FI73214C (sv)
FR (1)	FR2516083A1 (sv)
GB (1)	GB2112382B (sv)
GR (1)	GR77055B (sv)
IE (1)	IE54327B1 (sv)
IL (1)	IL67155A (sv)
IT (1)	IT1205272B (sv)
NL (1)	NL8204225A (sv)
SE (1)	SE452884B (sv)
SU (1)	SU1189347A3 (sv)
ZA (1)	ZA828095B (sv)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3151912A1 (de) *	1981-12-23	1983-06-30	Schering Ag, 1000 Berlin Und 4619 Bergkamen	Neue ergolin-aminoderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel
PH21123A (en) *	1983-04-28	1987-07-27	Erba Farmitalia	Ergoline derivatives
DE3413657A1 (de) *	1984-04-09	1985-10-17	Schering AG, 1000 Berlin und 4709 Bergkamen	Neue ergoline
DE3587860D1 (de) *	1984-04-09	1994-07-28	Schering Ag	2-substituierte Ergolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel.
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1982
- 1982-10-29 GB GB08231053A patent/GB2112382B/en not_active Expired
- 1982-11-01 NL NL8204225A patent/NL8204225A/nl not_active Application Discontinuation
- 1982-11-01 SU SU823506255A patent/SU1189347A3/ru active
- 1982-11-01 US US06/438,259 patent/US4500712A/en not_active Expired - Fee Related
- 1982-11-01 FI FI823727A patent/FI73214C/sv not_active IP Right Cessation
- 1982-11-01 CS CS827752A patent/CS232000B2/cs unknown
- 1982-11-02 IL IL67155A patent/IL67155A/xx unknown
- 1982-11-02 AT AT0399682A patent/AT381091B/de not_active IP Right Cessation
- 1982-11-02 AU AU90090/82A patent/AU553903B2/en not_active Ceased
- 1982-11-02 IE IE2614/82A patent/IE54327B1/en unknown
- 1982-11-03 FR FR8218418A patent/FR2516083A1/fr active Granted
- 1982-11-03 GR GR69718A patent/GR77055B/el unknown
- 1982-11-04 JP JP57192620A patent/JPS5885886A/ja active Granted
- 1982-11-04 DE DE19823240727 patent/DE3240727A1/de not_active Ceased
- 1982-11-04 ZA ZA828095A patent/ZA828095B/xx unknown
- 1982-11-04 IT IT24077/82A patent/IT1205272B/it active
- 1982-11-04 SE SE8206282A patent/SE452884B/sv not_active IP Right Cessation
- 1982-11-04 CA CA000414917A patent/CA1191841A/en not_active Expired
- 1982-11-05 BE BE0/209409A patent/BE894927A/fr not_active IP Right Cessation
- 1982-11-05 CH CH6452/82A patent/CH650506A5/de not_active IP Right Cessation
- 1982-11-05 DK DK494882A patent/DK494882A/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
IE822614L (en)	1983-05-06
IE54327B1 (en)	1989-08-30
JPS5885886A (ja)	1983-05-23
JPS628433B2 (sv)	1987-02-23
CA1191841A (en)	1985-08-13
US4500712A (en)	1985-02-19
FR2516083A1 (fr)	1983-05-13
GR77055B (sv)	1984-09-05
SE8206282L (sv)	1983-05-07
CS775282A2 (en)	1984-01-16
IL67155A0 (en)	1983-03-31
DE3240727A1 (de)	1983-05-19
ATA399682A (de)	1986-01-15
SE8206282D0 (sv)	1982-11-04
AU553903B2 (en)	1986-07-31
IT1205272B (it)	1989-03-15
FI73214B (fi)	1987-05-29
DK494882A (da)	1983-05-07
SU1189347A3 (ru)	1985-10-30
FI823727L (fi)	1983-05-07
SE452884B (sv)	1987-12-21
CH650506A5 (de)	1985-07-31
IL67155A (en)	1985-07-31
BE894927A (fr)	1983-05-05
AU9009082A (en)	1983-05-12
NL8204225A (nl)	1983-06-01
FI823727A0 (fi)	1982-11-01
ZA828095B (en)	1983-09-28
GB2112382B (en)	1985-03-06
GB2112382A (en)	1983-07-20
FI73214C (sv)	1987-09-10
AT381091B (de)	1986-08-25
IT8224077A0 (it)	1982-11-04
FR2516083B1 (sv)	1984-05-25

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US4076820A (en)	1978-02-28	Benzoquinolizines and hypotensive compositions containing them
CS232000B2 (en)	1985-01-16	Manufacturing process of new ergoline derovatives
US4125620A (en)	1978-11-14	2-[(2',6'-Disubstituted-phenyl)-imino]-imidazolidines and salts thereof
GB2071095A (en)	1981-09-16	Heterocyclic compounds processes for their preparation and pharmaceutical compositions containing them
KR100717489B1 (ko)	2007-05-14	피리도피리미디논 화합물, 이의 제조 방법 및 이를함유하는 약제 조성물
KR880001317B1 (ko)	1988-07-23	이미다졸릴페닐 아미딘 유도체의 제조방법
HU198713B (en)	1989-11-28	Process for producing ergolin derivatives and pharmaceutical compositions containing them as active components
NZ203956A (en)	1985-11-08	Imidazo(1,2,-a)pyridine derivatives and pharmaceutical compositions
CA1051878A (en)	1979-04-03	Compounds with ergoline skeleton and a process for the preparation thereof
US4472398A (en)	1984-09-18	Condensed pyrimidines
US4734501A (en)	1988-03-29	N-alkylation of dihydrolysergic acid
US4432990A (en)	1984-02-21	5-Aminoimidazoles as immunoregulants
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US3822262A (en)	1974-07-02	Phenyl acetylimino-imidazolines and-hexahydropyrimidines
IL112364A (en)	1998-01-04	Pharmaceutical preparations containing 3-phenylsulfonyl-3,7-diazabicyclo [1.3.3] nonanan compounds for the treatment of heart rhythm disorders and certain new compounds and their preparation
US4024258A (en)	1977-05-17	Composition of and method for reducing hypertension with a 1-[1-(indol-3-ylethyl)-piperazin-4-yl]-3-substituted urea
US4452982A (en)	1984-06-05	Process for the preparation of nitrogen-bridgehead condensed pyrimidine compounds, and pharmaceutical compositions containing them
US4495189A (en)	1985-01-22	Condensed pyrimidines
CS220336B2 (en)	1983-03-25	Method of producing new guanidine derivatives
SU1258327A3 (ru)	1986-09-15	Способ получени 7-замещенных 9 @ -метоксимитозана
US4681881A (en)	1987-07-21	5-alkoxy-pyrido[4,3-d]pyrimidine derivatives
US4499269A (en)	1985-02-12	Fused 1,3,5-triazines
US4681885A (en)	1987-07-21	5-oxo-pyrido[4,3-]pyrimidine derivatives
US4720499A (en)	1988-01-19	Treating blood vessel diseases with pyrido[4,3-b][1,6]naphthyridine-derivatives
EP1047668B1 (en)	2003-05-21	Triazepinones, process for their preparation and their therapeutic application