CN109336869A - A kind of mesylate of STAT3 inhibitor and preparation method thereof and purposes - Google Patents
A kind of mesylate of STAT3 inhibitor and preparation method thereof and purposes Download PDFInfo
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Abstract
The invention belongs to field of medicinal chemistry, it is related to mesylate of a kind of STAT3 inhibitor and preparation method thereof and purposes, specifically, the present invention relates to 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1, 3, mesylate of 5- triazine -2- amine and preparation method thereof and purposes, 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl the amido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1, 3, the structure of 5- triazine -2- amine mesylate is as follows, its mesylate good water solubility, bioavilability is high, stability is good.
Description
Technical field
The invention belongs to field of medicinal chemistry, be related to mesylate of a kind of STAT3 inhibitor and preparation method thereof with
On the way, in particular it relates to 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -
4H- chromene -4- ketone group) -1,3,5- triazine -2- amine mesylate and preparation method thereof and purposes.
Background technique
Cancer is the general designation of a major class malignant tumour, its main feature is that without limitation, without end hyperplasia.Cancer cell makes patient's body
Interior nutriment is largely consumed, while releasing a variety of toxin, and human body is made to generate a series of symptoms, cause human body it is thin,
Inability, anaemia, loss of appetite, fever and serious organ function are impaired, cause necrotic hemorrhage concurrent infection, patient finally by
It is dead in organ failure.
Signal transduction and (the Signal Transducer and Activator of of activating transcription factor -3
Transcription-3, STAT3) be a kind of GAP-associated protein GAP that can be activated by different cytokine receptors, cell because
Carrier is served as during son-acceptor interaction, the inherence specificity for keeping signal to transmit in the cell, and pass through induction target
The effect effect of biostimulation is expressed in genetic transcription, other than participating in angiogenesis and immune response, also with the increasing of cell
It grows, survive, breaking up, the close associations such as anti-apoptotic.STAT3 is in kinds of tumor cells (including blood such as leukaemia, Huppert's disease
A variety of entity tumors such as liquid tumour and lung cancer, breast cancer, prostate cancer) in abnormal expression increase, generation with malignant tumour,
Develop closely related.
By inhibiting STAT3 activity to be expected to that cancer cell is made apoptosis occur to achieve the purpose that treating cancer, study recently
It was found that inhibiting STAT3 signal that can overcome the chemical drug resistance including kinds of tumors such as retinoblastoma, lung cancer, leukaemia
Property, successfully research and development are a new antitumor target to STAT3.Therefore, new STAT3 inhibitor is actively found for cancer
Treatment have particularly important meaning.
The chemical name of compound (I) is 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N-
(2- methyl -4H- chromene -4- ketone group) -1,3,5-triazines -2- amine, cell in vitro Activity determination find it to prostate gland cancer cell
DU-145 has good inhibitory activity, IC50Value is 8.6nM, is had a good application prospect.But in the patent medicine of compound (I)
During Journal of Sex Research, the inventors found that different compound (I) pharmaceutical salts it is water-soluble, in terms of have
Biggish difference.Therefore, further investigation, which is found, is suitble to medicinal 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl acylamino-
Phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5-triazines -2- amine salt type, it is very necessary.
Summary of the invention
On the one hand, the present invention provides 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- first
Base -4H- chromene -4- ketone group) -1,3,5-triazines -2- amine mesylate, 4- (9- ethyl -9H- carbazole -4- base) -6- (4- alkene
Propionamido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5-triazines -2- amine structural formula such as formula (I) shown in,
Mesylate good water solubility, bioavilability are high, stability is good,
On the other hand, the present invention provides 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2-
Methyl -4H- chromene -4- ketone group) -1,3,5-triazines -2- amine mesylate preparation method, comprising the following steps:
The compound of formula (1) is made in step a:2- hydroxy acetophenone acetylation；
Step b: the compound of formula (2) is made in the compound cyclization of formula (1)；
Step c: the compound of formula (3) is made in the compound bromo of formula (2)；
Step d: the compound amino of formula (3) replaces the compound that formula (4) are made；
The compound of formula (5) is made in step e:4- nitrobenzene methyl and biuret cyclization；
Step f: the compound of formula (6) is made in the compound chloro of formula (5)；
Step g: the compound of formula (6) reacts the compound that formula (7) are made with the compound of formula (4)；
Step h: the compound and 4- (4,4,5,5- tetramethyl -1,3,2- dioxolane borine) -9- ethyl-of formula (7)
The compound of formula (8) is made in 9H- carbazole reaction；
Step i: the compound reduction of formula (8) hydrogenates the compound that formula (9) are made；
Step j: the compound of formula (9) reacts the compound that formula (I) is made with acryloyl chloride；
Step k: the compound of formula (I) is reacted with methanesulfonic acid is made formula (I) compound methanesulfonic acid salt, and reaction route is as follows:
In some preferred embodiments, the solvent that formula (I) compound is reacted with methanesulfonic acid is selected from alcohol, ketone, acetic acid second
Ester or their mixture；In a further preferred embodiment, the solvent that formula (I) compound is reacted with methanesulfonic acid is selected from first
Alcohol, ethyl alcohol, normal propyl alcohol, isopropanol, acetone, methyl ethyl ketone, methyl iso-butyl ketone (MIBK), ethyl acetate or their mixture；?
In embodiment still more preferably, the solvent that formula (I) compound is reacted with methanesulfonic acid is selected from methanol, ethyl alcohol, acetone, acetic acid
Ethyl ester or their mixture.
In some preferred embodiments, the molar ratio that formula (I) compound is reacted with methanesulfonic acid is about 1:1-1.1；?
In further preferred embodiment, the molar ratio that formula (I) compound is reacted with methanesulfonic acid is about 1:1.
In some specific embodiments, formula (I) compound and methanesulfonic acid are in etoh solvent, according to formula (I) chemical combination
The molar ratio of object and methanesulfonic acid is 1:1, reacts 0.5-1h at room temperature to obtain the final product.
The third aspect, the present invention provides a kind of pharmaceutical compositions, contain 4- (9- ethyl -9H- carbazole -4- base) -6-
(4- allyl amido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine mesylate and pharmaceutically
Acceptable carrier.
Fourth aspect, the present invention provides 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N-
(2- methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine mesylate includes the 4- (9- ethyl -9H- carbazole -4-
Base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine mesylate
Pharmaceutical composition preparation for treat and/or the drug of pre- anti-cancer in application, the cancer includes but is not limited to forefront
Gland cancer.
Specific embodiment
The present invention is explained in more detail with reference to embodiments, the embodiment of the present invention is merely to illustrate technology of the invention
Scheme not limits the scope of the invention.
The preparation of 1 2- aminomethyl -4H- chromene -4- keto hydrochloride of embodiment
The preparation of step 1 2- acetoxy acetophenone
2- hydroxy acetophenone (100mmol), chloroacetic chloride (250mmol) and potassium carbonate (500mmol) are added in reaction flask,
300ml acetone is added, back flow reaction 12h, after reaction, water, ethyl acetate extraction, anhydrous sulphur is added in evaporating solvent under reduced pressure
Sour sodium is dry, is concentrated to give grease, directly throws in next step.
The preparation of step 2 2- methyl -4H- chromene -4- ketone
2- acetoxy acetophenone (50mmol) is weighed in reaction flask, 100ml DMSO is added and dissolves, at 0-5 DEG C in batches
It is added sodium hydrogen (150mmol), finishes, be warmed to room temperature stirring 3h and water, dilute hydrochloric acid tune pH are added into reaction solution after reaction
It is worth faintly acid, ethyl acetate extraction, anhydrous sodium sulfate is dry, is concentrated to give grease, and 100ml second is added into gained grease
Acid and 5 drop concentrated hydrochloric acids, back flow reaction about 3h, reaction terminate, reaction solution are spin-dried for, and water, ethyl acetate extraction, anhydrous slufuric acid is added
Sodium is dry, and column chromatographic purifying obtains title compound.
ES:M/Z 161 [M+H]+。
The preparation of step 3 2- bromomethyl -4H- chromene -4- ketone
By step 2 gained 2- methyl -4H- chromene -4- ketone (10mmol), N-bromosuccinimide (NBS, 10mmol) and
Benzoyl peroxide (BPO, 0.95mmol) is added in reaction flask, and 20ml carbon tetrachloride is added to dissolve, back flow reaction 12h, reaction knot
Shu Hou, reaction solution add water, and ethyl acetate extraction, anhydrous sodium sulfate is dry, and column chromatographic purifying obtains title compound.
ES:M/Z 239 [M+H]+。
The preparation of step 4 2- aminomethyl -4H- chromene -4- keto hydrochloride
Step 3 gained 2- bromomethyl -4H- chromene -4- ketone (0.5mmol) is added in reaction flask, it is molten that 5ml DMF is added
Solution is added 2ml ammonium hydroxide, 12h is stirred at room temperature, and after reaction, water, ethyl acetate extraction is added in reaction solution, and anhydrous sodium sulfate is done
Dry, filtering is spin-dried for, and ethyl acetate 5ml is added, and the ethyl acetate hydrogen chloride solution of saturation is added after stirring and dissolving to supernatant layer nothing
Precipitating generates, and filters, dry, obtains title compound.
ES:M/Z 239 [M+H]+。
The preparation of chloro- 6- (4- the nitrobenzophenone) -1,3,5- triazine of 2 2,4- of embodiment bis-
The preparation of step 1 4- nitrobenzene methyl
4- nitrobenzoic acid (250mmol) is weighed in reaction flask, the dissolution of 300mL methanol is added, thionyl chloride is added dropwise
(375mmol) drips and finishes back flow reaction 12h, and after reaction, decompression is spin-dried for, and saturated sodium bicarbonate solution is added and adjusts pH to 7-
8, ethyl acetate extraction, anhydrous sodium sulfate is dry, is concentrated to give title compound, directly throws in next step.
The preparation of step 2 6- (4- nitrobenzophenone) -1,3,5- triazine -2,4- (1H, 3H)-diketone
Biuret (100mmol) is weighed in reaction flask, the dissolution of 150mL glycol dimethyl ether is added, adds in batches at 0-5 DEG C
Enter sodium hydride (83.4mmol), finish, be stirred to react 1h at 50 DEG C, adds 4- nitrobenzene methyl (83.4mmol), add
Finish, be warming up to 85 DEG C of reaction 20h and be after reaction poured into water reaction solution, adjusts pH to acidity with concentrated hydrochloric acid, filter, filter
Cake drying, obtains title compound.
ES:M/Z 235 [M+H]+。
The preparation of step 3 2,4- bis- chloro- 6- (4- nitrobenzophenone) -1,3,5- triazine
6- (4- nitrobenzophenone) -1,3,5-triazines -2,4- (1H, 3H)-diketone (200mmol) is added in reaction flask, is added
Entering 200mL phosphorus oxychloride, phosphorus pentachloride (800mmol), reaction solution is poured into water by 105 DEG C of reaction 12h after reaction, and two
Chloromethanes extraction, anhydrous sodium sulfate is dry, is concentrated to give title compound.
ES:M/Z 275 [M+H]+。
The chloro- 6- of 3 4- of embodiment (4- nitrobenzophenone)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine
Preparation
Chloro- 6- (4- the nitrobenzophenone) -1,3,5- triazine (50mmol) of 2 gains 2,4- of embodiment bis- is weighed in reaction flask
In, the dissolution of 100mL tetrahydrofuran is added, 1 gains 2- aminomethyl -4H- chromene -4- keto hydrochloride 2- (trifluoro of embodiment is added
Methyl)-pyridine -4- amine (55mmol), sodium carbonate (100mmol), back flow reaction 72h, filtering, column chromatographic purifying obtains title compound
Object.
ES:M/Z 416 [M+H]+。
The preparation of 4 4- of embodiment (4,4,5,5- tetramethyl -1,3,2- dioxolane borine) -9- ethyl -9H- carbazole
The preparation of the chloro- 9- ethyl -9H- carbazole of step 1 4-
4- chlorine carbazole (5.46mmol) is weighed in reaction flask, 20mL THF dissolution is added, is cooled to -10 DEG C, NaH is added
(14mmol), finishes, and after stirring 30 minutes, adds bromoethane (6mmol), finishes, reacts at room temperature 3h, and reaction terminates, and water quenching is added to go out,
Ethyl acetate extraction, dry, concentration is prepared chromatogram purification and obtains the chloro- 9- ethyl -9H- carbazole of 4-.
ES:M/Z 230 [M+H]+。
The preparation of step 2 4- (4,4,5,5- tetramethyl -1,3,2- dioxolane borine) -9- ethyl -9H- carbazole
Weigh the chloro- 9- ethyl -9H- carbazole (1mmol) of step 1 gains 4-, connection pinacol borate (1.1mmol), vinegar
Sour potassium (2mmol) and 1,1'- bis(diphenylphosphino) ferrocene dichloropalladium (Pd (dppf) Cl2, 2mmol) and in reaction flask, add
Entering 5mL1,4- dioxane, for 24 hours, after reaction, water is added in 100 DEG C of reactions under the conditions of nitrogen protection, ethyl acetate extraction,
Merge organic phase, saturated common salt water washing merges organic phase, dries, filters, and is concentrated, and column chromatographic purifying obtains title compound.
5 4- of embodiment (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5- triazine -2- amine preparation
Step 1 4- (9- ethyl -9H- carbazole -4- base) -6- (4- nitrobenzophenone)-N- (2- methyl -4H- chromene -4- ketone
Base) -1,3,5- triazine -2- amine preparation
In 30ml microwave reaction bottle, embodiment 3 gained mixture 4- chloro- 6- (4- nitrobenzophenone)-N- (2- is sequentially added
Methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine (10mmol), 4 gains 4- (4,4,5,5- tetramethyl-of embodiment
1,3,2- dioxolane borine) -9- ethyl -9H- carbazole (10mmol), [bis- (diphenylphosphine) ferrocene of 1,1'-] dichloride
Palladium dichloromethane complex (0.1mmol), x-phos (0.4mmol), cesium carbonate (100mmol) and 1,4- dioxane/H2O
(60ml/10ml), dissolution, argon gas displacement, 105 DEG C of microwave reaction 90min, concentration, column chromatographic purifying obtain title compound.
ES:M/Z 575 [M+H]+。
Step 2 4- (9- ethyl -9H- carbazole -4- base) -6- (4- aminophenyl)-N- (2- methyl -4H- chromene -4- ketone
Base) -1,3,5- triazine -2- amine preparation
Weigh step 1 gains 4- (9- ethyl -9H- carbazole -4- base) -6- (4- nitrobenzophenone)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5-triazines -2- amine (1mmol), 10%Pd-C (10mg) in reaction flask, be added 15ml methanol, at 1
Normal atmosphere pressure, H21h is restored, reaction is stopped, title compound is concentrated in filtering, is directly used in next step.
ES:M/Z 545 [M+H]+。
Step 3 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- chromene -
4- ketone group) -1,3,5- triazine -2- amine preparation
Weigh step 2 gains 4- (9- ethyl -9H- carbazole -4- base) -6- (4- aminophenyl)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5-triazines -2- amine (0.1mmol), diisopropylethylamine (0.3mmol) in reaction flask, be added 15ml
Anhydrous methylene chloride dissolution, is slowly dropped into methylene chloride (1ml) solution dissolved with allyl acyl chlorides (0.12mmol), 10min
Fully reacting, concentration, column chromatographic purifying obtain title compound.
1H NMR(600MHz,CDCl3) (δ, ppm): 10.12 (s, 1H), 8.12 (m, 1H), 7.80~7.82 (m, 2H),
7.78~7.79 (m, 1H), 7.67~7.69 (m, 2H), 7.50~7.52 (m, 2H), 7.43~7.45 (m, 2H), 7.31~
7.32 (m, 2H), 7.07~7.09 (m, 2H), 6.97~6.99 (m, 1H), 6.68~6.70 (m, 1H), 6.02~6.04 (m,
1H), 5.56 (s, 1H), 5.50~5.52 (m, 1H), 4.88 (s, 1H), 4.46~4.51 (m, 3H), 3.06~3.08 (m, 2H),
2.81~2.84 (m, 2H), 2.01~2.03 (brs, 2H), 1.91~1.93 (brs, 1H), 1.30~1.31 (t, 3H)
ES:M/Z 599 [M+H]+。
Embodiment 6:4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5- triazine -2- amine mesylate preparation
5 compound of embodiment (0.5mmol) is weighed in reaction flask, adds ethyl alcohol 10mL, at room temperature after stirring and dissolving, is added dropwise
Methanesulfonic acid acetone soln (containing methanesulfonic acid 0.5mmol) 1mL, drop finish, continue to stir 0.5h, evaporating solvent under reduced pressure, room temperature at room temperature
Lower vacuum drying obtains title compound.
Embodiment 7:4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5- triazine -2- amine mesylate preparation
5 compound of embodiment (0.5mmol) is weighed in reaction flask, adds ethyl acetate 10mL, at room temperature after stirring and dissolving,
Methanesulfonic acid acetone soln (contain methanesulfonic acid 0.55mmol) 1mL is added dropwise, drop finishes, continue to stir 0.5h at room temperature, evaporating solvent under reduced pressure,
Vacuum drying obtains title compound at room temperature.
Experimental example 1: biological activity determination
Compound prepares: the full-automatic microwell plate pretreatment system of POD810 is prepared the embodiment of the present invention 5 and embodiment 6
Compound be added in orifice plate, compound initial concentration is 100uM, and each compound does duplicate hole, 2 times of dilutions, 10 points.
The culture of cell: prostate gland cancer cell DU-145, human breast cancer cell MDA-MB-468 are used contain 15% tire respectively
The RPMI-1640 culture medium of cow's serum (FBS) is cultivated in 37 degree of incubators, and logarithmic growth phase cell is for testing.
The experiment of MTT cells viability: prostate gland cancer cell DU-145, human breast cancer cell MDA-MB-468 are inoculated with respectively
(5-10 × 10 in 96 orifice plates4Cells/well), 48h is handled with the compound of embodiment 5 and 6 respectively, 20 μ is added in every hole
L 3- (4,5- dimethylthiazole -2) -2,5- diphenyltetrazolium bromide bromide (MTT) hatches 4h, and 100 μ l in every hole is then added
DMSO sets low-speed oscillation 10min on shaking table, dissolves crystal sufficiently.It is measured at enzyme-linked immunosorbent assay instrument OD 490nm each
The light absorption value in hole handles to obtain homologous thread and IC using GraphPad Prism50Value, the results are shown in Table 1.
Table 1
The experimental results showed that the present invention is thin to the active MDA-MB-468 cell of STAT3, DU-145 with sustained activation
Born of the same parents have good inhibiting effect.
The water-soluble evaluation of experimental example 2
By pharmacopeia four water-soluble experiments in 2015, experimental result was shown in Table 2.
Table 2
| Compound | It is water-soluble |
| 6 compound of embodiment | 50.48mg/ml |
3 stability study of experimental example
Weigh 3 parts of 4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- color
Alkene -4- ketone group) -1,3,5-triazines -2- amine mesylate 1.0g, it is laid in culture dish respectively, 1 part of opening is placed in illumination illumination
To place 10 days under the conditions of 4500Lx ± 500Lx, 1 part of opening, which is placed under the conditions of 85% relative humidity of room temperature (RH), places 10 days, and 1
Part opening, which is placed under the conditions of 95% relative humidity of room temperature (RH), places 10 days, samples in the 0th, 5,10 day, examination largest single impurity, always
The variation of impurity, experimental result are shown in Table 3.
Table 3
Above-mentioned experimental result shows 4- of the invention (9- ethyl -9H- carbazole -4- base) -6- (4- acrylyl aminobenzene
Base)-N- (2- methyl -4H- chromene -4- ketone group) -1,3,5- triazine -2- amine mesylate have good chemical stability.
Claims (7)
1.4- (9- ethyl -9H- carbazole -4- base) -6- (4- allyl amido phenyl)-N- (2- methyl -4H- chromene -4- ketone group) -
The mesylate of 1,3,5-triazines -2- amine, structural formula are as follows:
2. the preparation method of mesylate described in claim 1, comprising the following steps:
The compound of formula (1) is made in step a:2- hydroxy acetophenone acetylation；
Step b: the compound of formula (2) is made in the compound cyclization of formula (1)；
Step c: the compound of formula (3) is made in the compound bromo of formula (2)；
Step d: the compound amino of formula (3) replaces the compound that formula (4) are made；
The compound of formula (5) is made in step e:4- nitrobenzene methyl and biuret cyclization；
Step f: the compound of formula (6) is made in the compound chloro of formula (5)；
Step g: the compound of formula (6) reacts the compound that formula (7) are made with the compound of formula (4)；
Step h: the compound and 4- (4,4,5,5- tetramethyl -1,3,2- dioxolane borine) -9- ethyl -9H- click of formula (7)
Azoles reacts the compound that formula (8) are made；
Step i: the compound reduction of formula (8) hydrogenates the compound that formula (9) are made；
Step j: the compound of formula (9) reacts the compound that formula (I) is made with acryloyl chloride；
Step k: the compound of formula (I) is reacted with methanesulfonic acid is made formula (I) compound methanesulfonic acid salt, and reaction route is as follows:
3. preparation method as claimed in claim 2, it is characterised in that: the solvent that formula (I) compound is reacted with methanesulfonic acid is selected from
Alcohol, ketone, ethyl acetate or their mixture；Preferably, the solvent that formula (I) compound is reacted with methanesulfonic acid is selected from methanol, second
Alcohol, acetone, ethyl acetate or their mixture.
4. preparation method as claimed in claim 2, it is characterised in that: the molar ratio that formula (I) compound is reacted with methanesulfonic acid is
About 1:1-1.1；Preferably, the molar ratio that formula (I) compound is reacted with methanesulfonic acid is about 1:1.
5. the pharmaceutical composition comprising mesylate and pharmaceutically acceptable carrier described in claim 1.
6. pharmaceutical composition described in mesylate described in claim 1 and claim 5 is in preparation for treating and/or pre-
Application in the drug of anti-cancer.
7. application as claimed in claim 6, the cancer is prostate cancer.
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2018
- 2018-10-31 CN CN201811283109.5A patent/CN109336869A/en not_active Withdrawn
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|---|---|---|---|---|
| CN1578663A (en) * | 2001-09-14 | 2005-02-09 | 梅特希尔基因公司 | Inhibitors of histone deacetylase |
| US20140045908A1 (en) * | 2011-02-25 | 2014-02-13 | Synta Pharmaceuticals Corp. | Hsp90 inhibitory compounds in treating jak/stat signaling-mediated cancers |
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| Title |
|---|
| A. STEPHEN K. HASHMI， 等: "Gold(I)-Catalyzed Rearrangement of 3-Silyloxy-1,5-enynes: An Efficient Synthesis of Benzo[b]thiophenes, Dibenzothiophenes, Dibenzofurans, and Indole Derivatives" * |
| CARMEN ESCOLANO，等: "Aryl radical cyclisation onto pyrroles" * |
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