49545-52-0Relevant academic research and scientific papers
Structure-activity relationship study of tricyclic necroptosis inhibitors
Jagtap, Prakash G.,Degterev, Alexei,Choi, Sungwoon,Keys, Heather,Yuan, Junying,Cuny, Gregory D.
, p. 1886 - 1895 (2008/02/03)
Necroptosis is a regulated caspase-independent cell death mechanism that can be induced in multiple cell types and is characterized by morphological features resembling necrosis. Here we describe a series of tricyclic heterocycles (i.e., 3-phenyl-3,3a,4,5-tetrahydro-2H-benz[g]indazoles, 3-phenyl-2,3,3a,4-tetrahydro-[1]benzopyrano[4,3-c]pyrazoles, 3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles, and 5,5-dioxo-3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles], collectively termed Nec-3, that can potently inhibit necroptosis. For example, compounds 8, 22, 41, 53, and 55 inhibit necroptosis in an FADD-deficient variant of human Jurkat T cells treated for 24 h with TNF-α with EC50 values in the range 0.15-0.29 μM. Distinct from the previously described series of hydantoin-containing indole derivatives (Nec-1), the Nec-3 series exhibits specificity in inhibiting TNF-α-induced necroptosis. A structure-activity relationship (SAR) study revealed that the (3R,3aR)-rel-diastereomers were more active than the (3R,3aS)-rel-diastereomers for all four ring systems. Introduction of fluorine or methoxy to the 8-position of the tricyclic ring and a methoxy to the 4-position of the pendent phenyl ring increased activity. Amides at the 2-position of the tricyclic ring were best. The Nec-3 series provides new tools for elucidating caspase-independent cell death pathways and potentially lead compounds for therapeutic development.
Synthesis of 3,3a-trans/cis-2-phenyl/acetyl-3-aryl-tetrahydroindeno/naphtho-and hexahydrobenzocycloheptapyrazoles as antiimplantation agents
Sinha, Anoop Kumar,Rastogi, Shri Nivas
, p. 684 - 692 (2007/10/02)
Reaction of benzocycloalkanones (1-3 and 24) and araldehydes (4-6) gives the arylideno-alkanones (7-12, 25 and 26) of which 11 and 12 on alkylation and acetylation afford alkyl ethers (13, 14 and 17) and acetates (15 and 16) respectively.Condensation of a
Heterocycles. Part VIII. Synthesis of New Substituted Benzindazoles
El-Rayyes, N. R.,Al-Jawhary, A.
, p. 135 - 140 (2007/10/02)
Aryl aldehydes I reacted with α-tetralone to give the corresponding 2-arylidene-1-tetralone II.Condensation of the latter chalcones with hydrazine, methylhydrazine and phenylhydrazine produced the corresponding benzoindazoles III, V and VI respectively
