170508-14-2Relevant articles and documents
BICYCLIC CARBOXAMIDES AND METHODS OF USE THEREOF
-
Paragraph 1036; 1037, (2019/10/29)
Compounds, compositions and methods are provided for modulating the activity of EP2 and EP4 receptors, and for the treatment, prevention and amelioration of one or more symptoms of diseases or disorders related to the activity of EP2 and EP4 receptors. In certain embodiments, the compounds are antagonists of both the EP2 and EP4 receptors.
(±)-N9-(2-(hydroxymethyl)spiro[3.3]hept-6-yl)adenine. The first biologically active saturated analogue of adenallene with axial dissymmetry
Jones,Drach,Corbett,Kessel,Zemlicka
, p. 6277 - 6280 (2007/10/03)
Synthesis of the title analogue 2 is described. Fecht's acid (3) was esterified with N,N-dimethylformamide dimethyl acetal to give monoester 4 along with diester 5. Compound 4 was transformed to ester amide 6 by the reaction with isobutyl chloroformate and triethylamine followed by ammonolysis. Hoffman rearrangement of 6 effected by lead tetraacetate in tert-butyl alcohol led to the N-tert-butoxycarbonyl ester 7. The latter was reduced with Ca(BH4)2 to give the protected amino alcohol 8. Removal of the N-tert-butoxycarbonyl group with 2 M HCl in methanol afforded the hydrochloride of amino alcohol 2. Reaction of 9 with 5-amino-4,6-dichloropyrimidine and triethylamine gave the pyrimidine derivative 10 which, in turn, was cyclized to 6-chloropurine 11a. Ammonolysis of the latter intermediate afforded the title analogue 2. The 1H NMR spectrnm of Fecht's acid (3) in CD3COCD3 showed that four methylene protons were magnetically nonequivalent (two quartets) whereas the other four were equivalent, forming a single doublet. Compound 2 inhibited the replication of human cytomegalovirus (IC50 32 μM) and growth of murine leukemia L1210 cells (IC50 30 μM). Zone assays showed inhibition of the following tumor cultures at 0.5 mg/disk: murine leukemia P388, mouse tumors PO3, C38, and M17/Adr as well as human tumors MCF-7 and CX-1.