CN1067891A - Novel barberry alkane derivatives and contain the medicament of this compounds and their preparation method - Google Patents
Novel barberry alkane derivatives and contain the medicament of this compounds and their preparation method Download PDFInfo
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- CN1067891A CN1067891A CN91104205A CN91104205A CN1067891A CN 1067891 A CN1067891 A CN 1067891A CN 91104205 A CN91104205 A CN 91104205A CN 91104205 A CN91104205 A CN 91104205A CN 1067891 A CN1067891 A CN 1067891A
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- medicament
- barberry
- compound
- salt
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to novel barberry alkane derivatives, also relate to the medicament that contains these compounds and their preparation.
In formula (I), R
1And R
2Represent methylene-dioxy together, R
3Represent the alkyl of 1-6 carbon atoms.
Description
The present invention relates to novel barberry alkane derivatives, also relate to the medicament that contains these compounds and their preparation method.
In the Rauwolfia plant section, has the alkaloid-barberry alkane of physiologically active, in many aspects the better pharmacologically active that demonstrates than indoles.The α of barberry alkane
2-receptor blocking activity (for example, can be referring to ViZi, E, S, Toth, I., Somogyi, G.T., Szabo, L.Barsing, L.G. and Szdntay, cs
2J.of Med Chem medical chemistry magazine 30,1355(1987). European patent EP No 202950) be valuable especially.
The purpose of this invention is to provide a class novel cpd, this compounds is than known α
2-adrenoceptor agonist drug has better choice, thereby can be successfully used to treatment.
The racemize of the formula I that obtains in experimental study process of the present invention and optically-active are novel 13, and the little alkane derivatives of 14-two dehydrogenations has been found out and can have been satisfied these needs
In the formula:
R
1And R
2Represent together methylene-dioxy and
R
3Representative has the straight or branched alkyl of 1-6 carbon atom
According to preparation method of the present invention, formula I novel 13,14-two dehydrogenation barberry alkane derivatives, wherein R
1, R
2And R
3With the racemize or the optically-active of above-mentioned identical-available formula II, 14-hydroxy derivatives elimination of water prepares.
R in the formula
1, R
2And R
3All same as described above
Elimination of water can be realized (referring to L.Szabo I.Toth, L.Toke, Cs.Szantay by known Fei Er David Smail reaction (German Chinese translation) (V.Ismeier reaction); " Libiee is uncommon " chemical record event (Liebigs Ann Chem 1971,642).Being reflected at the dimethylamino benzophenone acid amides exists down.Do to carry out in the cancellation agent with thionyl chloride.Acceptable acid-respons on gained matrix and the physiology (for example, hydrochloric acid, sulfuric acid, citric acid, tartrate) is converted into salt, because these compounds are more suitable for using in biotechnological formulation.
The starting compound of formula II is published among the European patent EP No.202 950 and can makes by the method for narrating in the patent, here cites with for referencial use.
Demonstrate α according to novel cpd of the present invention
2The antagonistic activity of-adrenoceptor so they can use, can be made activeconstituents by the present invention in medicament, and can arbitrarily mix use with other known active compounds.
Can prepare with any known method according to medicament of the present invention, for example use the compound or their salt of formula I to mix arbitrarily with known additives (for example thinner, solvent, lubricant, weighting material etc.), and the mixture that obtains made the form that is suitable for taking, for example non-enterally administer, oral medicine or rectal application.Making medicament can be, for example tablet, pill, soup, and the suspension soup, medicinal powder, spray can prepare.
7, the 8-(methylene-dioxy) (chemical compounds I is preferably to select for use in the formula I compound a) to the other barberry alkane of-13,14 two dehydrogenations-13-carboxylate methyl ester, compares with Yohimbine, shows effectively α
2The antagonistic activity of-adrenoceptor.And this compound does not have any α
1The blocking-up activity of-adrenoceptor.
+ electricity irritation mouse vas deferens, Bayer-1470 antagonistic;
++ mouse vas deferens, a synephrine stimulant
(referring to Vizi, E.S. etc.; Pharmacology and experimental therapeutic magazine (J.pharmacol.Exp.Ther) 1986,288,701-706, Vizi, E.S. etc.: medicine and pharmacology magazine (J.Med.Chem) 1987.
Mean value ± standard error of mean; Provided the experiment number in the bracket;
Competition
The present invention elaborates by the following examples
Embodiment 1
7, the 8-(methylene-dioxy)-13, the other barberry alkane of 14-two dehydrogenations-(chemical compounds I a) is equivalent to the compound of formula I, in the formula to the 13-carboxylate methyl ester
R
1，R
2＝OCH
2O，
R
3＝COOCH
3
C
1-H，C
12-H，C
17-H＝α
At 7 of 2 grams (5.56 mmole), the 8-(methylene-dioxy)-solution that the other barberry alkane-13-carboxylate methyl ester of 14-hydroxyl and 20 milliliters dimethylamino benzophenone acid amides are made in, the thionyl chloride (being dissolved in 20 milliliters of dimethyl formamides) that in the time of 0 ℃, adds 4 milliliters, and room temperature placement 2 days.Mixture is poured in 100 milliliters of frozen water then, uses dense NH
4OH makes alkalize (to PH=9) with the sedimentation and filtration of separating out, drying and with ether or recrystallizing methanol.
Yield: 1.8 grams (94.8%); 187-189 ℃ of fusing point (hydrochloride) (methyl alcohol)
Ultimate analysis: C
20H
23NO
4(341.39)
Calculate: C70.36 H6.79 N4.10
Actual measurement: C70.31 H6.78 N4.05
Mass spectrum: m/z% 341/79/, 340/100/,
326/79/，310/7/，300/25/，
282/12/1，254/0.8/1，252/1/
240/4/，226/7/，216/17/，
214/20/，202/8/，189/83/，
176/9/，175/21/，174/22/
Nuclear magnetic resonance spectrum/CDCl
3/:
7.00/1H，m，C
14-H/，6.74，
6.53/2H，S，C
6-H，C
9-H/，5.86
5.86/2H，S，OCH
2O/，3.77/3H，
S，COOCH
3/
Infrared spectra/KBr/:1720/COOCH
3/, 1650cm
-1/ C=C/.
Embodiment 2
The hydrochloride of chemical compounds I a
The matrix I a of 1 gram (2.93 mmole) mixes with 5 ml methanol and is acidified to PH=3 with hydrochloric acid/methanol mixture of 30%, then with sedimentary crystallisate drying, uses 1: 1 methanol mixture to wash again.
Yield: 1.05 grams (95%); Fusing point: 187-189 ℃ (methyl alcohol)
Claims (7)
1, the preparation method of the racemize of formula I or optically-active compound and salt thereof
In the formula: R
1And R
2Represent methylene-dioxy together
R
3Representative has the alkyl of the straight or branched of 1-6 carbon atom
It is characterized in that elimination of water from the racemize of formula II or optically-active compound
In the formula: R
1, R
2And R
3All same as described above--can disassemble arbitrarily and obtain the formula I compound or the formula I compound is transformed salify or changes into these salt free
2, according to the method for claim 1, it is characterized in that: exist in dimethyl formamide and use the thionyl chloride elimination of water down
3, racemize in the structure formula I or optically-active compound and their salt, R in the formula
1, R
2And R
3All require in 1 identical with aforesaid right.
4,7, the 8-(methylene-dioxy)-13,14-two dehydrogenations-other barberry alkane-13-carboxylate methyl ester.
5,7, the 8-(methylene-dioxy)-13,14-dideoxy-other barberry alkane-13-carboxylate methyl ester-hydrochloride.
6, preparation medicament method is characterized in that the compound or its salt with one or more formula I, R in the formula
1, R
2And R
3All require in 1 identically, mix, then the mixture of gained is made the medicament that is suitable for taking with acceptable additive on one or more pharmacology with aforesaid right.
7, medicament is characterised in that the compound that contains one or more formula I or their salt, R in the formula
1, R
2And R
3All require in 1 identical with aforesaid right.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA914043A ZA914043B (en) | 1990-06-18 | 1991-05-28 | Building block manufacture |
| CN91104205A CN1067891A (en) | 1990-06-18 | 1991-06-22 | Novel barberry alkane derivatives and contain the medicament of this compounds and their preparation method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA904711 | 1990-06-18 | ||
| ZA914043A ZA914043B (en) | 1990-06-18 | 1991-05-28 | Building block manufacture |
| CN91104205A CN1067891A (en) | 1990-06-18 | 1991-06-22 | Novel barberry alkane derivatives and contain the medicament of this compounds and their preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1067891A true CN1067891A (en) | 1993-01-13 |
Family
ID=36778161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN91104205A Pending CN1067891A (en) | 1990-06-18 | 1991-06-22 | Novel barberry alkane derivatives and contain the medicament of this compounds and their preparation method |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1067891A (en) |
| ZA (1) | ZA914043B (en) |
-
1991
- 1991-05-28 ZA ZA914043A patent/ZA914043B/en unknown
- 1991-06-22 CN CN91104205A patent/CN1067891A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ZA914043B (en) | 1992-03-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |