Novel Steroid- heterocyclic Derivatives as possible therapeutic compounds for Management of Alzheimer's disease in experimental model
Dina Said AbouElyazeed El-Kady;
Abstract
A number of novel hybrid steroid and curcumin derivatives were synthesized with different substituent fused to the essential starting moiety. The structures of all of the synthesized compounds were confirmed by their spectral and analytical data; IR, 1H NMR, ¹³C NMR and Mass spectra which all agreed with the assigned structures. The prepared compounds were evaluated as anti-Alzheimer's agents.
When curcumin was allowed to react with 3β-hydroxy -17-hydrazone -5α-androstane derivative in boiling ethanol in presence of acetic acid as a catalyst it yielded the hybrid Bis-(andorstanhydrazono)curcumin derivative 4 (Scheme 1).
Scheme 1
When curcumin 1 was submitted to react with phenyl thiosemicarbazide in boiling ethanol afford 5 (Scheme 2).
Scheme 2
Interaction of curcumin 1 with diethyl malonate in the presence of sodium methoxide in boiling ethanol yielded 6(Scheme 3).
Scheme 3
When curcumin 1 was allowed to react with chloroacetyl chloride in pyridine with stirring 24 hours at room temperature yielded 7 Scheme 4.
Scheme 4
When the diazonium salt of Z-aminotetrahydrobenzothiophene carbonitrile derivative was coupled with Curcumin 1 in acetic acid and sodium acetate yielded the coupling product 8. Similarly, when curcumin 1 was submitted to react with 2-aminobenzo]b [thiophene(diazonium salt) in acetic acid and sodium acetate it yielded 9 (Scheme 5).
Scheme 5
When compound 8 or 9 were allowed to react with hydrazines namely, hydrazine hydrate, phenyl hydrazine, and or thiosemicarbazide or cyanoaceticacidhydrazide in boiling ethanol in presence of Et3N it afforded the pyrazole derivatives 10a-d or 11a-d (Scheme 6).
Scheme 6
When a solution of compound 8 in boiling ethanol was allowed to react with ethylcyanoacetate or malononitrile in presence of catalytic amount of piperidine, 12 and 13 respectively (Scheme 7).
Scheme 7
When curcumin 1 was submitted to react with 2-(3-oxoandrost-4-en-17-yl-amino)benzoic acid in boiling benzene (30mL) and H2SO4 (3mL) it yielded 14 (Scheme 8).
Scheme 8
When compound 2 was submitted to react with sulpha drugs namely, sulphathiazole (a), sulphamethoisooxazole (b) and sulphadiazine (c) in least amount of glacial acetic acid in an oil bath at 120oC, it yielded phenylpyrazolocurcminsulfa derivatives 15, 16 and 17 respectively (Scheme 9).
Scheme 9
When compound 3 was submitted to react with sulpha drugs namely, sulphathiazole (a), sulphamethoisooxazole (b) and sulphadiazine (c) (suspension in glacial acetic acid in an oil bath at 120oc), it afforded isoxazolocurcuminsulpha derivatives (18 a-c) (Scheme 10).
When curcumin was allowed to react with 3β-hydroxy -17-hydrazone -5α-androstane derivative in boiling ethanol in presence of acetic acid as a catalyst it yielded the hybrid Bis-(andorstanhydrazono)curcumin derivative 4 (Scheme 1).
Scheme 1
When curcumin 1 was submitted to react with phenyl thiosemicarbazide in boiling ethanol afford 5 (Scheme 2).
Scheme 2
Interaction of curcumin 1 with diethyl malonate in the presence of sodium methoxide in boiling ethanol yielded 6(Scheme 3).
Scheme 3
When curcumin 1 was allowed to react with chloroacetyl chloride in pyridine with stirring 24 hours at room temperature yielded 7 Scheme 4.
Scheme 4
When the diazonium salt of Z-aminotetrahydrobenzothiophene carbonitrile derivative was coupled with Curcumin 1 in acetic acid and sodium acetate yielded the coupling product 8. Similarly, when curcumin 1 was submitted to react with 2-aminobenzo]b [thiophene(diazonium salt) in acetic acid and sodium acetate it yielded 9 (Scheme 5).
Scheme 5
When compound 8 or 9 were allowed to react with hydrazines namely, hydrazine hydrate, phenyl hydrazine, and or thiosemicarbazide or cyanoaceticacidhydrazide in boiling ethanol in presence of Et3N it afforded the pyrazole derivatives 10a-d or 11a-d (Scheme 6).
Scheme 6
When a solution of compound 8 in boiling ethanol was allowed to react with ethylcyanoacetate or malononitrile in presence of catalytic amount of piperidine, 12 and 13 respectively (Scheme 7).
Scheme 7
When curcumin 1 was submitted to react with 2-(3-oxoandrost-4-en-17-yl-amino)benzoic acid in boiling benzene (30mL) and H2SO4 (3mL) it yielded 14 (Scheme 8).
Scheme 8
When compound 2 was submitted to react with sulpha drugs namely, sulphathiazole (a), sulphamethoisooxazole (b) and sulphadiazine (c) in least amount of glacial acetic acid in an oil bath at 120oC, it yielded phenylpyrazolocurcminsulfa derivatives 15, 16 and 17 respectively (Scheme 9).
Scheme 9
When compound 3 was submitted to react with sulpha drugs namely, sulphathiazole (a), sulphamethoisooxazole (b) and sulphadiazine (c) (suspension in glacial acetic acid in an oil bath at 120oc), it afforded isoxazolocurcuminsulpha derivatives (18 a-c) (Scheme 10).
Other data
| Title | Novel Steroid- heterocyclic Derivatives as possible therapeutic compounds for Management of Alzheimer's disease in experimental model | Other Titles | مشتقات استرويديه حلقيه غير متجانسه جديده كمركبات علاجيه محتمله للسيطره على مرض الزهايمرفى نموذج تجريبى | Authors | Dina Said AbouElyazeed El-Kady | Issue Date | 2015 |
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