180793-00-4Relevant academic research and scientific papers
Molecular modelling insights into a physiologically favourable approach to eicosanoid biosynthesis inhibition through novel thieno[2,3-b]pyridine derivatives
Mohamed, Mosaad S.,Mansour, Yara E.,Amin, Hatem K.,El-Araby, Moustafa E.
, p. 755 - 767 (2018)
In this research, we exploited derivatives of thieno[2,3-b]pyridine as dual inhibitors of the key enzymes in eicosanoid biosynthesis, cyclooxygenase (COX, subtypes 1 and 2) and 5-lipoxygensase (5-LOX). Testing these compounds in a rat paw oedema model revealed potency higher than ibuprofen. The most active compounds 7a, 7b, 8b, and 8c were screened against COX-1/2 and 5-LOX enzymes. Compound 7a was the most powerful inhibitor of 5-LOX with IC50 = 0.15 μM, while its p-chloro analogue 7b was more active against COX-2 (IC50 = 7.5 μM). The less desirable target COX-1 was inhibited more potently by 8c with IC50 = 7.7 μM. Surflex docking programme predicted that the more stable anti- conformer of compound (7a) formed a favourable complex with the active site of 5-LOX but not COX-1. This is in contrast to the binding mode of 8c, which resembles the syn-conformer of series 7 and binds favourably to COX-1.
Synthesis of some new pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and pyrido[3′,2′: 4,5]thieno[2,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives
Ho, Yuh-Wen
, p. 1163 - 1174 (2007/10/03)
2,3-Disubstituted-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4( 3H) -ones 8a-8c, 9a-9c were obtained by treatment of pyrido[3′,2′:4,5]thieno[3,2-d][1,3]oxazin-4(3H)-one derivative 3, 3-diacetylamino-thieno[2,3-b]pyridine derivative 5 and 3-ethoxymethyleneaminothieno[2,3-b]pyridine derivative 7a with appropriate amines, respectively. Condensation of compounds 8b, 9b with appropriate α-chlorocarbonyl compounds gave the corresponding 3-substituted carbonylmethylene-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives 13a-d. 3-N-Substituted-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 15a,b, 16a,b and 18a,b were also obtained by cyclization of carbohydrazide 14 with different reagents under a variety of conditions. On the other hand, cyclization of 3-amino-4-imino-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 21a,b with appropriate orthoesters afforded the corresponding 3,5-dialkyl-pyrido[3′,2′:4,5]thieno[2,3-e]-1,2,4-triazolo[1,5-c] pyrimidines 22a-f.
Synthesis of new 2-[(substituted-pyrazol-1-yl)carbonyl]-thieno[2,3-b]pyridine derivatives using 1,3-diketones, alkylethoxymethylenes and ketene dithioacetals
Ho, Yuh-Wen
, p. 947 - 953 (2007/10/03)
The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide (1) with appropriate 1,3-diketones 2a-2d in glacial acetic acid afforded 3-amino-2-[(3,5-disubstituted-pyrazol-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b] pyridines 3a-3d. 3-Amino-2-[(5-amino-3,4-disubstituted-pyrazol-1-yl)carbonyl]-4,6- dimethylthieno[2,3-b]pyridines 5a-5h were also prepared by treatment of carbohydrazide 1 with appropriate alkylethoxymethylenes and ketene dithioacetals 4a-4h, respectively.
