- FUNCTIONALIZED HETEROCYCLES AS ANTIVIRAL AGENTS
-
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Paragraph 0231
(2020/04/10)
-
- Facile preparation of protected benzylic and heteroarylmethyl amines via room temperature Curtius rearrangement
-
A step-wise, room temperature procedure for acyl azide formation and the subsequent Curtius rearrangement of phenyl and heteroaryl acetic acids is described. We have developed a protocol for room temperature Curtius rearrangement in MeOH or CHCl3 that provides an improvement over standard conditions, avoiding the use of additives or heat. This room temperature optimization of the Curtius rearrangement prevents the formation of side products often observed with benzylic acids, allowing access to a variety of benzylic and heteroarylmethyl amines.
- Leathen, Matthew L.,Peterson, Emily A.
-
supporting information; experimental part
p. 2888 - 2891
(2010/06/14)
-
- 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697): Identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists
-
P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.
- Kaila, Neelu,Janz, Kristin,Huang, Adrian,Moretto, Alessandro,DeBernardo, Silvano,Bedard, Patricia W.,Tam, Steve,Clerin, Valerie,Keith Jr., James C.,Tsao, Desirée H.H.,Sushkova, Natalia,Shaw, Gray D.,Camphausen, Raymond T.,Schaub, Robert G.,Wang, Qin
-
-
- Intramolecular carbenoid insertions: Reactions of α-diazo ketones derived from furanyl-, thienyl-, (benzofuranyl)-, and (benzothienyl)acetic acids with rhodium(II) acetate
-
α-Diazo ketones tethered to furan, benzofuran, thiophene, and benzothiophene by a single methylene spacer have been shown to undergo atypical, rhodium(II) acetate catalyzed chemistry. For example, while treatment of 1-diazo-3-(3-furanyl)-2-propanone with Rh2(OAc)4 resulted in the expected 2-(4-oxo-2-cyclopentenylidene)acetaldehyde, isomeric 1-diazo-3- (2-furanyl)-2-propanone undergoes a vinylogous Wolff rearrangement and in the presence of water gives a mixture of 6a-methyl-2,3,3a,6a-tetrahydrofuro [2,3- b]furan-2-one and 2-(2-methyl-3-furyl)acetic acid. Rhodium acetate catalyzed decomposition of 1-diazo-3-(3-benzofuranyl)-2-propanone and 1-diazo-3-(2- benzofuranyl)-2-propanone are also shown to undergo vinylogous Wolff rearrangement despite the fact that this chemistry is not observed with homologous benzofuranyl systems. α-Diazo ketones derived from benzothienyl propionic acids undergo the expected cyclization with 1-diazo-4-(3- benzothienyl)-2-butanone and 1-diazo-4-(2-benzothienyl)-2-butanone giving rise to 1,2,3,4-tetrahydrodibenzo[b,d]thiophen-3-one and 1,2,3,4- tetrahydrodibenzo[b,d]thiophen-2-one, respectively. While decomposition of 1- diazo-3(3-benzothienyl)-2-propanone resulted in the formation of 2,3-dihydro- 1H-benzo[b]cyclopenta[d]thiophen-2-one, the isomeric 1-diazo-3-(2- benzothienyl)-2-propanone gave a dimer which resulted from a [3 + 2] cycloaddition followed by a [1,3]-alkyl shift. Overall, the results from this study of intramolecular carbenoid insertion into five-membered heteroaromatic systems show that the resultant chemistry is dependent on the nature of the heteroatom, position of substitution, and the length of the aliphatic tether.
- Yong, Kelvin,Salim, Mohamed,Capretta, Alfredo
-
p. 9828 - 9833
(2007/10/03)
-