Synthesis and Neurotropic Activity of Novel Condensed Cyclopentanopyrido[3 ' ,2 ' :4,5]-Thieno[3,2- D ]Pyrimidine Deriva
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Pharmaceutical Chemistry Journal, Vol. 54, No. 7, October, 2020 (Russian Original Vol. 54, No. 7, July, 2020)
SYNTHESIS AND NEUROTROPIC ACTIVITY OF NOVEL CONDENSED CYCLOPENTANOPYRIDO[3¢,2¢:4,5]THIENO[3,2-d]PYRIMIDINE DERIVATIVES V. V. Dabaeva,1,* M. R. Bagdasaryan,1 E. G. Paronikyan,1 Sh. Sh. Dashyan,1 R. G. Paronikyan,1 I. M. Nazaryan,1 and A. G. Akopyan1 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 7, pp. 27 – 32, July, 2020.
Original article submitted August 18, 2019. 2-Oxo-2,5,6,7-tetrahydro-3-cyano-1H-cyclopenta[b]pyridine was used as the starting point to develop an accessible synthesis of condensed cyclopentanopyrido[3¢,2¢:4,5]thieno[3,2-d]pyrimidine derivatives. The neurotropic activity of these compounds was studied, and a number of them showed anticonvulsant activity as antagonism to corasol. Compound II, like diazepam, had anti-anxiety and activating effects, while the other compounds had sedative activity. Keywords: synthesis, cyclopentanopyrido[3¢,2¢:4,5]thieno[3,2-d]pyrimidine, neurotropic activity.
logical properties [4 – 6], so there is interest in studying the properties of analogous derivatives containing a cyclopentane ring. The starting compound for synthesis of these latter substances was 2-oxo-2,5,6,7-tetrahydro-3-cyano-1H-cyclopenta[b]pyridine-3-carbonitrile (I) [7]. Boiling of I with phosphorus oxychloride was used to synthesize the 2-chloro derivative II, interaction of which with the ethyl ester of thioglycolic acid yielded the amino ester of condensed thieno[2,3-b]pyridine III (Scheme 1). The Nimentovsky re-
Thieno[3,2-d]pyrimidines are of undoubted interest in the search for novel biologically active compounds, as evidenced by the extensive literature [1 – 3]. Studies of the biological properties of thieno- and furopyridines previously synthesized in our work and condensed with the tetrahydropyrane ring showed these compounds to have valuable bio1
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Science and Technology Center for Organic and Pharmaceutical Chemistry, National Academy of Sciences of the Republic of Armenia, 26 Azatutyan Prospekt, 0014 Erevan, Armenia. e-mail: [email protected]
Scheme 1 CN
I
N H
O
POCl3
HSCH 2COOC 2H 5
,8h
N II N
HCONH 2 ,2h
NH 2
CN
N
,6h
N N
NH C 5H 5N,
,2h
N
S VI
COOC 2H 5
O
H 2NCSNH 2 N C 2H 5OH,
S
,2h
Cl
V N
N N
S III
POCl3
S IV
C 2H 5ONa,
Cl
N
N
NH
S S
SH
707 0091-150X/20/5407-0707 © 2020 Springer Science+Business Media, LLC
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V. V. Dabaeva et al.
action, run by heating amino ester III in formamide, led to cyclization to form a pyrimidine ring (compound IV). The influences of the type of substituent in this compound on its biological activity were investigated by running the chlorodehydroxylation reaction with phosphorus oxychloride followed by substitution of the chlorine atom with thiourea to form thiol VI. This latter can exist in the thiolactam and thiolactime forms. The NH group signal at 3120 cm-1 in the IR spectrum indicates a preference for the thione form. However, substitution reactions with various halogenides invo
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