CS200717B1 - S-substituted derivatives of 8-chlor-10,11-dihydrodibenzo/b,f/thiepin-10-thioles - Google Patents
S-substituted derivatives of 8-chlor-10,11-dihydrodibenzo/b,f/thiepin-10-thioles Download PDFInfo
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- CS200717B1 CS200717B1 CS280478A CS280478A CS200717B1 CS 200717 B1 CS200717 B1 CS 200717B1 CS 280478 A CS280478 A CS 280478A CS 280478 A CS280478 A CS 280478A CS 200717 B1 CS200717 B1 CS 200717B1
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- dihydrodibenzo
- chloro
- thiepin
- thioles
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- -1 3-diethylaminopropyl Chemical group 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- BISQTCXKVNCDDA-UHFFFAOYSA-N thiepine Chemical compound S1C=CC=CC=C1 BISQTCXKVNCDDA-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229960003279 thiopental Drugs 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 3
- 229910001626 barium chloride Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000004899 motility Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-M 3-carboxy-2-(carboxymethyl)-2-hydroxypropanoate Chemical compound OC(=O)CC(O)(C(O)=O)CC([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-M 0.000 description 2
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229960004266 acetylcholine chloride Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- GRTOGORTSDXSFK-XJTZBENFSA-N ajmalicine Chemical compound C1=CC=C2C(CCN3C[C@@H]4[C@H](C)OC=C([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 GRTOGORTSDXSFK-XJTZBENFSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- XJVIPPHGDPEDJL-UHFFFAOYSA-N thiourea;hydrochloride Chemical compound Cl.NC(N)=S XJVIPPHGDPEDJL-UHFFFAOYSA-N 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- INDZTCRIYSRWOH-UHFFFAOYSA-N undec-10-enyl carbamimidothioate;hydroiodide Chemical compound I.NC(=N)SCCCCCCCCCC=C INDZTCRIYSRWOH-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Vynález ee týká S-eubatitučnich derivátů 8-chlor-10,ll-dihydrodibenzo(b,f)thiapin-10-thiolu obecného vzorce IThe invention relates to the S-eubstituted 8-chloro-10,11-dihydrodibenzo (b, f) thiapine-10-thiol derivatives of the general formula I
a jejich aoll e farmaceuticky nezávadnými anorganickými nebo organickými kyselinami.and pharmaceutically acceptable inorganic or organic acids thereof.
Látky vzorce I a Jejich soli ee vyznačuji pestrým apektrem neurotropních efektů, což je činí použitelnými jako léčiva. Z hlediska centrálních efektů, jsou látky podle vynálezu trankvilizéry a sedativy použitelnými v psychiatrii a neurologii ke zklidňováni agitovaných pacientů a dále pacientů trpících stavy úzkoeti, strachu a různými fóbiemi.The compounds of formula I and their salts are characterized by a diverse spectrum of neurotrophic effects, making them useful as medicaments. In terms of central effects, the compounds of the invention are tranquilizers and sedatives useful in psychiatry and neurology to soothe agitated patients and patients suffering from anxiety, fear and various phobias.
V testech na zvířatech se centrálně tlumivá účinnost projevuje potenciaci thiopentalovéhe spánku, lnhlbici spontánní motllity zvířat, hypothermickým, protikřečovým a antiamfetamlnovýn efektem.In animal tests, centrally depressant efficacy is manifested by potentiation of thiopental sleep, deepening of spontaneous animal motility, hypothermic, anticonvulsant and antiamphetamine effects.
Z periferních efektů látek podle vynálezu jeou typické účinky epaemolytické, které se projevuji Jako vůči acetylcholinovým, tak 1 baryumchloridovým kontrakcím hladkéhoThe peripheral effects of the compounds according to the invention are typical epaemolytic effects, which are manifested both against acetylcholine and 1 barium chloride contractions of smooth
200 717200 717
ZOO 717 svalu. Antlcholinsrgni komponenta účinku je- potvrzena táž mydrlitickým účinkem.Látky podlí vynálezu jsou tedy použitelná táž pro uvolňováni spastických stavů hladkých evalč, zvláště zažívacího traktu. Jejich antihietaminový účinek je činí použitelnými při alergických onemocněních. Konečně byl u nich zaznamenán táž účinek lokálně eneetetieký.ZOO 717 muscle. The anticholinergic component of action is confirmed by the same mydrlitic effect. Thus, the compounds of the present invention are useful in releasing spastic states of smooth evalvae, especially the gastrointestinal tract. Their antihietamine effect makes them useful in allergic diseases. Finally, they have the same locally enethetic effect.
Typickými látkami podle vynálezu jsou S-(8-chlor-lO,ll-dihydrodibsnzo/b,f/thyepin-10-yl)ieothiuroniumchlorid (II) , 8-chlor-10-(2-dimsthylaminosthylthio)-10,ll-dihydrodlbanzo(b,f)thiepin (III), který byl testován ve formě hydrochíoridu a konečně 8-chlor-lO(3-dimethylaminopropylthio)-10,ll-dihydrodibenzo(b,f) thiepin (XV), testovaný ve formě dihydrogencitrátu.Typical compounds of the present invention are S- (8-chloro-10,11-dihydrodibenzo [b, f] thyepin-10-yl) iothiuronium chloride (II), 8-chloro-10- (2-dimethylamino-ethylthio) -10,11-dihydrodlbanzo (b, f) thiepine (III), which was tested in the form of the hydrochloride and finally 8-chloro-10 (3-dimethylaminopropylthio) -10,11-dihydrodibenzo (b, f) thiepine (XV), tested in the form of dihydrogen citrate.
Látka II je při orálním podání velmi málo toxiekát její střední emrtná dávka pro myši *-D50 je 1,5 g/kg. V orální dávce 100 až 300 mg/kg látka signifikantně potencuje thiopentalový spánek. U normotensnich krys vyvolává orální dávka 300 mg/kg pokles krevního tlaku o 17 % trvající asi 1 hodinu. Na izolovaném krysím duodenu v testu ln vitro působí látka spasmolyticky proti acetylchollnovým 1 baryumchlorldovým spasmům v koncentracích 1 až 10 ug/ml. V testu detoxikace histeminu u morčat vykazuje látke v orální dávce 100 mg/kg antihietaminový efekt, projevující se tím, že chrání 50 X zvířat před letálnlm efektem 5 mg/kg intrajugulárně aplikovaného histamlnu.Substance II is on oral administration very low toxiekát emrtná its mid dose mice * -D 50 is 1.5 g / kg. At an oral dose of 100 to 300 mg / kg, the substance significantly potentiates thiopental sleep. In normotensive rats, an oral dose of 300 mg / kg causes a 17% decrease in blood pressure lasting about 1 hour. In the isolated rat duodenum in an in vitro test, the compound acts spasmolytically against acetylcholine 1 barium chloride spasm at concentrations of 1 to 10 µg / ml. In a guinea pig detoxification test in guinea pigs, an oral dose of 100 mg / kg exhibits an antihietamine effect by protecting 50 X animals from the lethal effect of 5 mg / kg of intra -ugularly administered histamine.
Hydrochlorid látky III byl rovněž podáván většinou orálně; jeho střední smrtná dávka u myši LD50 je 2,0 g/kg. V dávce 300 mg/kg, látka signifikantně inhibuje spontánní motilitu myši. v dávkách 50 až 100 mg/kg potencuje thiopentalový spánek u myši.Compound III hydrochloride was also administered mostly orally; its mean lethal dose in the LD 50 mouse is 2.0 g / kg. At a dose of 300 mg / kg, the agent significantly inhibited the spontaneous motility of the mouse. at doses of 50 to 100 mg / kg potentiates thiopental sleep in the mouse.
V dávkách 100 až 300 mg/kg sa projevuje její hypothermický efekt u krys, Oávka 100 mg/kg Je účinná protikřečově u myši v testu elektroěoku. V dávkách poněkud vyšších než 300 mg/kg má látka mydriatický účinek u myši (rozšiřuje průměr zornice o 100 %), Podobně Jako u předešlá látky lze konstatovat spasmolytická působeni v testu ln vitro vůči acetylcholinovým i baryumchlorldovým kontrakcím v koncentraci 1 až 10 ug/ml. Hypoteneivnl efekt u normotensnich krys je krátkodobější než u předešlé látky : dávka 100 až 300 mg/kg vyvolává pokles krevního tlaku o 10 % ne dobu 10 minut. Antihietaminový efekt Je ve srovnáni s předešlou látkou asi 2 až 4 vyšší; účinné jsou již děvky 25 sž 50 mg/kg.At doses of 100-300 mg / kg, it exhibits its hypothermic effect in rats. A dose of 100 mg / kg is effective in anti-convulsive mice in an electro-eye test. At doses slightly higher than 300 mg / kg, the substance has a mydriatic effect in mice (extending the pupil diameter by 100%). Similarly to the previous compound, spasmolytic effects in the in vitro test against both acetylcholine and barium chloride contractions at a concentration of 1 to 10 µg / ml . The hypotensive effect in normotensive rats is shorter than the previous compound: a dose of 100 to 300 mg / kg causes a decrease in blood pressure of 10% over 10 minutes. Antihietamine Effect It is about 2 to 4 higher compared to the previous substance; whores 25 to 50 mg / kg are already effective.
Oihydrogencitrát látky IV byl ve většině testů podáván peretsrálně. Akutní toxicita u myši při intravenosnim podáni, L050, je 60 mg/kg. Subkutánnl dávky 5-12 mg/kg signifikantně inhibuji spontánní motilitu myěi. Potenciacs thiopentalováho opánku u myši se projevuje v intravenosnich dávkách 2,5 až 5,0 mg/kg. Antihietaminový efekt jo zřejmý v intravenosni dávce 12 mg/kg. Látka má lokálně ansststickě působeni v testu rohovkové anestesle u králíků i koncentrace 0,5 až 1,0 % je účinná u 50 % zvířat. Spssmolytický účinek v testu in vitro vůči scstylcholinu 1 bsryumchloridu Je stejný Jako u obou předchozích látek.Oihydrogen citrate IV was administered peresally in most tests. Acute toxicity in mice upon intravenous administration, 50 L0 is 60 mg / kg. Subcutaneous doses of 5-12 mg / kg significantly inhibited spontaneous motility in mice. Potency of the thiopental vein in mice is demonstrated at intravenous doses of 2.5 to 5.0 mg / kg. The antihietamine effect is evident at an intravenous dose of 12 mg / kg. The substance has a local anesthetic action in the corneal anesthesia test in rabbits and a concentration of 0.5 to 1.0% is effective in 50% of the animals. The spmolytic effect in the in vitro test against scchylcholine 1 bsryum chloride is the same as the two previous substances.
V příkladech provedení jsou popsány způsoby přípravy látek podle tohoto vynálezu. Společnou výchozí látkou je 8,10-dichlor-l0,ll-dlhydrodibenzo(b,f)thiepln (3. O. Jílek e spol., Collect. Czech. Chem. Commun. 33, 1831, 19681. který ss v prvá řadě alkyluje thiomočovlnou. Získá se S-(8-chlor-lO,ll-dlhydrodibsnzo/b,f/thiapin-10-yl)lsothiuroniumZOO 71 chlorid (II). Oeho zahříváním a vodným hydroxidem sodným dochází k Štěpeni za vzniku 8-chlor-10,ll-dihydrodibenzo-(b,f)thiepin-10-thiolu. Sodná 801 táto látky poskytuje potom alkylaci 2-dimethyleminoethylchloridem nebo 3-dlmethylaminopropylchlorldem baeická thioethery III a IV, která ee převedou neutralieaci kyselinami na eoll. Oalěl podrobnosti způsobů přípravy látek podle vynálezu jeou patrná z příkladů provedeni.Methods for preparing the compounds of the present invention are described in the Examples. The common starting material is 8,10-dichloro-10,11-dlhydrodibenzo (b, f) thiepline (3 O. Jílek et al., Collect. Czech. Chem. Commun. 33, 1831, 19681), which is primarily S- (8-chloro-10,11-dihydrodibenzoyl, 1H, thiapin-10-yl) isothiuronium ZOO 71 chloride (II) is obtained, which is heated with aqueous sodium hydroxide and cleaved to give 8-chloro- Sodium 801 then provides alkylation with 2-dimethyleminoethyl chloride or 3-dimethylaminopropylchloride and the thioethers III and IV which convert the acid neutralization to the eol. according to the invention, it is evident from the examples.
Přiklad 1Example 1
S-(8-chlor-10,11-dihydrodlbenzo/b,f/thiepin-10-yl) isothiuroniumchlorid (II)S- (8-chloro-10,11-dihydrodibenzo [b, f] thiepin-10-yl) isothiuronium chloride (II)
Směs 9,0 g thiomočoviny, 60 ml 95 % ethanolu a 30 g 8,10-dichlor-10,ll-dihydrodibenzo (h,f)thiepinu ae vaří 10 hodin pod zpětným chladičem. Za horka ee zflltruje a filtrát se ponechá krystalizovat a získá es 21,6 g (57 %) látky t. 180 až 183 °C. Látka krystaluj ze směsi 95 % ethanolu a etheru Jako monohydrát, t.t. 183 až 184 °C.A mixture of 9.0 g of thiourea, 60 ml of 95% ethanol and 30 g of 8,10-dichloro-10,11-dihydrodibenzo (h, f) thiepine and refluxed for 10 hours. It is filtered while hot and the filtrate is crystallized to give 21.6 g (57%) of m.p. 180-183 ° C. The material crystallized from a mixture of 95% ethanol and ether as the monohydrate, m.p. Mp 183-184 ° C.
Přiklad 2Example 2
8-Chlor-10-(2-dimethylaminoethylthio)-10,ll-dihydrodibenzo(b.f)thiepin (III)8-Chloro-10- (2-dimethylaminoethylthio) -10,11-dihydrodibenzo (b.f) thiepine (III)
Směs 10,0 g monohydrátu látky II a 10 ml 5 M hydroxidu sodného sa vaří pod zpětným chladičem 2 hodiny v dusíková atmosféře. Po ochlazeni se okyselí 50 ml 1 M kyseliny sirové a produkt se izoluje extrakci benzenem. Zpracováním extraktu se zláká 7,3 g (94 %) 8-chlor-10,ll-dihydrodibanzo(b,f)thiepin-10-thiolu e t.t. 90 až 92 °C. Analytický vzorek 8 t.t. 93 až 94 °c ee získá kryetalizací z hexanu.A mixture of 10.0 g of II monohydrate and 10 ml of 5 M sodium hydroxide was refluxed for 2 hours under a nitrogen atmosphere. After cooling, it is acidified with 50 ml of 1 M sulfuric acid and the product isolated by extraction with benzene. Treatment of the extract yielded 7.3 g (94%) of 8-chloro-10,11-dihydrodibanzo (b, f) thiepine-10-thiol, m.p. Mp 90-92 ° C. Analytical sample 8 m.p. 93 DEG-94 DEG C. was obtained by crystallization from hexane.
Ve 30 ml ethanolu ee rozpustí 0,6 g sodíku, k roztoku se přidá 5,6 g předešlého thiolu a 3,0 g 2-dimethylaminoethylchloridu a směs se vaří 2 hodiny pod zpětným chladičem Po odpařeni ethanolu za anižanáho tlaku se zbytek rozloží vodou e produkt se extrahuje benzenem. Extrakt se protřepe 8 přebytečnou 1:1 zředěnou kyselinou chlorovodíkovou: vyloučí ee 4,5 g (58 %) krystalického hydrochloridu produktu, t.t. 210 až 213 °C. Analytický vzorek, t.t. 210 až 214 °C (voda).0.6 g of sodium are dissolved in 30 ml of ethanol, 5.6 g of the preceding thiol and 3.0 g of 2-dimethylaminoethyl chloride are added to the solution and the mixture is refluxed for 2 hours. After evaporating the ethanol under vacuum, the residue is decomposed with water. the product was extracted with benzene. The extract was shaken with 8 excess 1: 1 dilute hydrochloric acid. Mp 210-213 ° C. Analytical sample, m.p. 210 DEG -214 DEG C. (water).
Přiklad 3Example 3
8-Chlor-10-(3-dimethylaminopropylthio)~10,ll-dihydrodibenzo(b,fthiepin (IV)8-Chloro-10- (3-dimethylaminopropylthio) -10,11-dihydrodibenzo (b, phthiepine (IV))
Podobně jako v předešlém případě ee provede reakce 6,0 g thiolu s 3,2 g 3-dimethyl aminopropylchloridu ve 30 ml ethanolu, ve kterém se předem rozpustí 0,6 g sodíku. Po protřepáni benzenového roztoku base s přebytečnou zředěnou kyselinou chlorovodíkovou se zíeká vodný roztok hydrochloridu, který se oddělí, base se uvolni hydroxidem amonným a izoluje znovu extrakci benzenem; 6,9 g (90 %) oleje. Neutralizaci kyselinou citrónovou v ethanolu se získá krystalický dihydrogencitrát 8 t.t. 122 až 124 °C za rozkladuAs in the previous case, 6.0 g of thiol are reacted with 3.2 g of 3-dimethyl aminopropyl chloride in 30 ml of ethanol, in which 0.6 g of sodium is previously dissolved. After shaking the benzene solution of the base with excess dilute hydrochloric acid, the aqueous hydrochloride solution is separated, separated, the base released with ammonium hydroxide and isolated again by benzene extraction; 6.9 g (90%) of an oil. Neutralization with citric acid in ethanol gave crystalline dihydrogen citrate 8 m.p. 122 DEG-124 DEG C. with decomposition
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS280478A CS200717B1 (en) | 1978-05-02 | 1978-05-02 | S-substituted derivatives of 8-chlor-10,11-dihydrodibenzo/b,f/thiepin-10-thioles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS280478A CS200717B1 (en) | 1978-05-02 | 1978-05-02 | S-substituted derivatives of 8-chlor-10,11-dihydrodibenzo/b,f/thiepin-10-thioles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS200717B1 true CS200717B1 (en) | 1980-09-15 |
Family
ID=5366195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS280478A CS200717B1 (en) | 1978-05-02 | 1978-05-02 | S-substituted derivatives of 8-chlor-10,11-dihydrodibenzo/b,f/thiepin-10-thioles |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS200717B1 (en) |
-
1978
- 1978-05-02 CS CS280478A patent/CS200717B1/en unknown
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