DD152559A5 - Verfahren zur herstellung eines antagonisten - Google Patents

Verfahren zur herstellung eines antagonisten Download PDF

Info

Publication number: DD152559A5
Authority: DD; German Democratic Republic
Prior art keywords: acid; fluorodibenzo; thiepin; substituent; carboxylic acid
Prior art date: 1979-06-01

Application number

DD80221520A

Other languages

German (de)

English (en)

Inventor

Joshua Rokach

Edward J Cragoe

Clarence S Rooney

Original Assignee

Merck & Co Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1979-06-01

Filing date

1980-06-02

Publication date

1981-12-02

1980-06-02 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1981-12-02 Publication of DD152559A5 publication Critical patent/DD152559A5/de

Links

239000005557 antagonist Substances 0.000 title claims description 4
238000004519 manufacturing process Methods 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 56
WWDUZVXKZJPKNB-UHFFFAOYSA-N thiepine-3-carboxylic acid Chemical compound OC(=O)C1=CSC=CC=C1 WWDUZVXKZJPKNB-UHFFFAOYSA-N 0.000 claims abstract description 14
239000000203 mixture Substances 0.000 claims description 60
239000002253 acid Substances 0.000 claims description 35
238000000034 method Methods 0.000 claims description 22
101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
150000002148 esters Chemical class 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
150000004820 halides Chemical class 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
238000004587 chromatography analysis Methods 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
230000003287 optical effect Effects 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
150000008064 anhydrides Chemical group 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
125000006178 methyl benzyl group Chemical group 0.000 claims description 3
SAHGCTPARQWSQG-UHFFFAOYSA-N 3-fluoro-11-oxobenzo[b][1]benzothiepine-9-carboxylic acid Chemical compound C1=CC2=CC(F)=CC=C2S(=O)C2=CC(C(=O)O)=CC=C21 SAHGCTPARQWSQG-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
125000004404 heteroalkyl group Chemical group 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
229910021645 metal ion Inorganic materials 0.000 claims description 2
RKEXPBCMGJAOLM-UHFFFAOYSA-N n-methyl-2-phenylacetamide Chemical compound CNC(=O)CC1=CC=CC=C1 RKEXPBCMGJAOLM-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
102100040141 Aminopeptidase O Human genes 0.000 claims 1
108050008333 Aminopeptidase O Proteins 0.000 claims 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims 1
229910052757 nitrogen Inorganic materials 0.000 claims 1
208000006673 asthma Diseases 0.000 abstract description 9
238000011282 treatment Methods 0.000 abstract description 6
BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 abstract description 5
201000009961 allergic asthma Diseases 0.000 abstract description 3
208000026935 allergic disease Diseases 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
-1 PGF 2 Chemical class 0.000 description 19
239000007787 solid Substances 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
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238000001914 filtration Methods 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
230000007062 hydrolysis Effects 0.000 description 12
238000006460 hydrolysis reaction Methods 0.000 description 12
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
150000003180 prostaglandins Chemical class 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
150000003857 carboxamides Chemical class 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
239000000575 pesticide Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
IUHXGZHKSYYDIL-UHFFFAOYSA-N 2-(2-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1I IUHXGZHKSYYDIL-UHFFFAOYSA-N 0.000 description 8
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
230000003647 oxidation Effects 0.000 description 8
238000007254 oxidation reaction Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
230000002378 acidificating effect Effects 0.000 description 7
125000000896 monocarboxylic acid group Chemical group 0.000 description 7
229940094443 oxytocics prostaglandins Drugs 0.000 description 7
229920005989 resin Polymers 0.000 description 7
239000011347 resin Substances 0.000 description 7
150000003839 salts Chemical class 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
229910052500 inorganic mineral Inorganic materials 0.000 description 6
235000010755 mineral Nutrition 0.000 description 6
239000011707 mineral Substances 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
239000003513 alkali Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000002089 prostaglandin antagonist Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000000926 separation method Methods 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
239000002904 solvent Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
HNGQQUDFJDROPY-UHFFFAOYSA-N 3-bromobenzenethiol Chemical compound SC1=CC=CC(Br)=C1 HNGQQUDFJDROPY-UHFFFAOYSA-N 0.000 description 3
DESYAKABISSNRU-UHFFFAOYSA-N 3-fluorobenzo[b][1]benzothiepine-9-carboxylic acid Chemical compound C1=CC2=CC(F)=CC=C2SC2=CC(C(=O)O)=CC=C21 DESYAKABISSNRU-UHFFFAOYSA-N 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
150000002440 hydroxy compounds Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
150000004965 peroxy acids Chemical class 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
239000000725 suspension Substances 0.000 description 3
150000003551 thiepines Chemical class 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
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UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 2
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238000011287 therapeutic dose Methods 0.000 description 2
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230000003435 bronchoconstrictive effect Effects 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
150000001989 diazonium salts Chemical class 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
208000024711 extrinsic asthma Diseases 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
150000002780 morpholines Chemical class 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003140 primary amides Chemical class 0.000 description 1
239000000047 product Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000004317 sodium nitrate Substances 0.000 description 1
235000010344 sodium nitrate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
208000000995 spontaneous abortion Diseases 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000005720 sucrose 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
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
HPINPCFOKNNWNW-UHFFFAOYSA-N thiete Chemical compound C1SC=C1 HPINPCFOKNNWNW-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
239000010936 titanium Substances 0.000 description 1
150000003609 titanium compounds Chemical class 0.000 description 1
238000001665 trituration Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D337/14—[b,f]-condensed
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/50—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
- C07C205/51—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated
- C07C205/52—Nitro-acetic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

DD80221520A 1979-06-01 1980-06-02 Verfahren zur herstellung eines antagonisten DD152559A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US4444479A	1979-06-01	1979-06-01
US4444579A	1979-06-01	1979-06-01

Publications (1)

Publication Number	Publication Date
DD152559A5 true DD152559A5 (de)	1981-12-02

Family

ID=26721570

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD80221520A DD152559A5 (de)	1979-06-01	1980-06-02	Verfahren zur herstellung eines antagonisten

Country Status (13)

Country	Link
EP (1)	EP0023078B1 (da)
AU (1)	AU534849B2 (da)
DD (1)	DD152559A5 (da)
DE (1)	DE3067522D1 (da)
DK (1)	DK233180A (da)
ES (4)	ES491886A0 (da)
FI (1)	FI801638A7 (da)
GR (1)	GR68550B (da)
IE (1)	IE49833B1 (da)
NO (1)	NO801625L (da)
NZ (1)	NZ193765A (da)
PL (1)	PL121395B1 (da)
PT (1)	PT71280B (da)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NO811187L (no) *	1980-11-24	1982-05-25	Merck & Co Inc	Fremgangsmaate ved fremstilling av 7-fluor-dibenzo-(b,f)-thiepinderivater
US4472586A (en) *	1982-09-30	1984-09-18	Merck Frosst Canada, Inc.	6H-Dibenz[b,e][1,4]oxathiepin derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PT68303A (en) *	1977-07-26	1978-08-01	Merck & Co Inc	Process for the preparation of dibenzo/b,f/thiepin
IT7850376A0 (it) *	1977-07-26	1978-07-19	Merck & Co Inc	Composizioni di dibenzo(b.f)tiepina e procedimento per la loro preparazione

1980
- 1980-05-21 FI FI801638A patent/FI801638A7/fi not_active Application Discontinuation
- 1980-05-21 PT PT71280A patent/PT71280B/pt unknown
- 1980-05-22 GR GR62023A patent/GR68550B/el unknown
- 1980-05-27 ES ES491886A patent/ES491886A0/es active Granted
- 1980-05-30 IE IE1139/80A patent/IE49833B1/en unknown
- 1980-05-30 DK DK233180A patent/DK233180A/da not_active Application Discontinuation
- 1980-05-30 DE DE8080301811T patent/DE3067522D1/de not_active Expired
- 1980-05-30 AU AU58915/80A patent/AU534849B2/en not_active Ceased
- 1980-05-30 EP EP80301811A patent/EP0023078B1/en not_active Expired
- 1980-05-30 NZ NZ193765A patent/NZ193765A/xx unknown
- 1980-05-30 NO NO801625A patent/NO801625L/no unknown
- 1980-05-31 PL PL1980224662A patent/PL121395B1/pl unknown
- 1980-06-02 DD DD80221520A patent/DD152559A5/de unknown
1981
- 1981-02-11 ES ES499340A patent/ES8201998A1/es not_active Expired
- 1981-02-11 ES ES499341A patent/ES499341A0/es active Granted
- 1981-02-11 ES ES499339A patent/ES8201997A1/es not_active Expired

Also Published As

Publication number	Publication date
DE3067522D1 (en)	1984-05-24
EP0023078A1 (en)	1981-01-28
ES499339A0 (es)	1982-01-16
AU5891580A (en)	1980-12-04
ES8105728A1 (es)	1981-06-16
AU534849B2 (en)	1984-02-16
GR68550B (da)	1982-01-18
NO801625L (no)	1980-12-02
IE49833B1 (en)	1985-12-25
FI801638A7 (fi)	1981-01-01
ES8201999A1 (es)	1982-01-16
NZ193765A (en)	1984-07-31
DK233180A (da)	1980-12-02
ES499341A0 (es)	1982-01-16
PL121395B1 (en)	1982-04-30
ES499340A0 (es)	1982-01-16
ES8201998A1 (es)	1982-01-16
PL224662A1 (da)	1981-02-13
EP0023078B1 (en)	1984-04-18
ES8201997A1 (es)	1982-01-16
ES491886A0 (es)	1981-06-16
PT71280B (en)	1981-09-17
IE801139L (en)	1980-12-01
PT71280A (en)	1980-06-01

Publication	Publication Date	Title
DE1695853A1 (de)	1972-03-02	5-unsubstituierte und 5-oxosubstituierte Aza-Dibenzo-cycloheptene und Verfahren zu ihrer Herstellung
CH624949A5 (da)	1981-08-31
DD140746A5 (de)	1980-03-26	Verfahren zur herstellung von prostaglandinantagonisten
DE2907862C2 (da)	1987-10-08
DE2514389A1 (de)	1975-10-09	6-oxo-7-substituiert-6h-indeno- (5,4-b)-furan(und thiophen)carbonsaeuren
DE2224655A1 (de)	1972-12-07	Tricyclische Verbindungen und Verfahren zu deren Herstellung
DE1804691B2 (de)	1973-06-07	Taurocholensaeurederivate
DD152559A5 (de)	1981-12-02	Verfahren zur herstellung eines antagonisten
DE2624352C3 (de)	1979-06-28	Dibenzo [bfl thiepine, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende entzündungshemmende Zubereitungen
DE2841644C2 (da)	1989-09-21
CH643255A5 (en)	1984-05-30	4-Amino-2-(piperazin-1-yl or homopiperazin-1-yl)quinazoline derivatives, processes for their preparation and medicaments containing them
CH616934A5 (en)	1980-04-30	Process for the preparation of chromone derivatives
DE1470314C3 (da)	1975-02-20
DE3927370A1 (de)	1991-02-21	Verfahren zur herstellung von clausenamid und neoclausenamid und deren derivate
CH631452A5 (de)	1982-08-13	Halogen-benzofuranon-carbonsaeuren und verfahren zu deren herstellung.
CH618698A5 (da)	1980-08-15
DE2804777A1 (de)	1978-08-17	Verfahren zur herstellung von benzoheterocyclylglyoxylsaeurederivaten
CH510009A (de)	1971-07-15	Verfahren zur Herstellung von neuen heterocyclischen Carbonsäuren
AT371100B (de)	1983-05-25	Verfahren zur herstellung von neuen indan-1carbons[ure-derivaten und deren salzen
DD271330A5 (de)	1989-08-30	Verfahren zur herstellung von rechtdrehender 3-(3-pyridyl)-2h,3h-pyrrolo[1,2-c]]-thiazol-7-carbonsaeure
AT371099B (de)	1983-05-25	Verfahren zur herstellung von neuen indan-1carbons[ure-derivaten und deren salzen
DE1963824B2 (de)	1980-04-30	3-Benzylphenylessigsäurederivate, Verfahren zu ihrer Herstellung und Verwendung zur Herstellung von Derivaten der 2-(3-Benzoyl-2-hydroxyphenyl)-essigsäure
AT289128B (de)	1971-04-13	Verfahren zur Herstellung von neuen, in 8- und 10-Stellung substituierten 10, 11-Dihydrodibenzo[b,f]thiepinderivaten und deren Salzen
AT381938B (de)	1986-12-10	Verfahren zur herstellung von neuen spirobenzofuranonverbindungen
AT369732B (de)	1983-01-25	Verfahren zur herstellung von neuen 1,4-diphenylpyrazolderivaten