- MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
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Page/Page column 59-60
(2020/01/08)
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- Investigating the Underappreciated Hydrolytic Instability of 1,8-Diazabicyclo[5.4.0]undec-7-ene and Related Unsaturated Nitrogenous Bases
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The widespread use of amidine and guanidine bases in synthetic chemistry merits a thorough understanding of their chemical properties. The propensity of these reagents to hydrolyze under mild conditions and generate aminolactams and aminoureas, respectively, has not been adequately described previously. During the synthesis of uprifosbuvir (MK-3682), we became aware of this liability for 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) by observing the formation of an unexpected reaction impurity and traced the root cause to low levels of N-(3-aminopropyl)-?-caprolactam present in the commercial bottle. A controlled stability study over a period of two months at 25 °C demonstrated that, above a threshold water content, DBU steadily hydrolyzed over time. Rates of hydrolysis for DBU, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and N,N,N′,N′-tetramethylguanidine (TMG) in organic, aqueous, and mixed solvent systems were then measured to gain a more general appreciation of what conditions to avoid in order to maintain their integrity. Our findings indicate that these bases are hydrolytically unstable in unbuffered and very basic solutions but become significantly more stable in buffered solutions at pH values below 11.6.
- Hyde, Alan M.,Calabria, Ralph,Arvary, Rebecca,Wang, Xiao,Klapars, Artis
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supporting information
p. 1860 - 1871
(2019/10/11)
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- HIV INTEGRASE INHIBITORS
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The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
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- Synthesis of potentially bioactive PABA-related N-(aminoalkyl)lactamic amino acids and esters via selective SNAr reactions
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Potentially bioactive N-(aminoalkyl)lactamic amino acids and esters were synthesized in satisfactory to good yields by SNAr reactions of aromatic acids with N-(3-aminopropyl)lactams followed by esterification with tertiary amino alcohols. The addition-elimination SNAr mechanism was confirmed by NMR and MS measurements. Graphical Abstract: [Figure not available: see fulltext.]
- Goncalves, Renato S.,Abdelnur, Patricia V.,Santos, Vanessa G.,Simas, Rosineide C.,Eberlin, Marcos N.,Magalhaes, Alvicler,Perez Gonzalez, Eduardo R.
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experimental part
p. 197 - 204
(2011/10/05)
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- A comparative solid state 13C NMR and thermal study of CO 2 capture by amidines PMDBD and DBN
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The present work shows study of the CO2 capture by amidines DBN and PMDBD using 13C solid-state NMR and thermal techniques. The solid state 13C NMR analyses demonstrate the formation of a single PMDBD-CO2 product which was assigned to stable bicarbonate. In the case of DBN, it is shown that two DBN-CO2 products are formed, which are suggested to be stable bicarbonate and unstable carbamate. The role of water in the DBN-CO2 capture as well as the stability of the products to environmental moisture was also investigated. The results suggest that the carbamate formation is favored in dry DBN, but in the presence of water it decompose to form bicarbonate. Thermal analysis shows a good gravimetric CO 2 absorption of DBN. Release of CO2 was found to be almost quantitative from the PMDBDH+ bicarbonate about 110 °C.
- Pereira, Fernanda Stuani,Lincon Da Silva Agostini, Deuber,Do Espirito Santo, Rafael Dias,Deazevedo, Eduardo Ribeiro,Bonagamba, Tito Jose,Job, Aldo Eloizo,Gonzalez, Eduardo Rene Perez
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scheme or table
p. 2146 - 2153
(2011/10/09)
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- Synthesis and evaluation of novel N-substituted-6-methoxynaphthalene-2- carboxamides as potential chemosensitizing agents for cancer
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A novel class of molecules with structure N-[3-(heteroaryl)propyl]-6- methoxynaphthalene-2-carboxamides 8-13 were synthesized by condensing 6-methoxy-2-naphthoyl chloride 1 with 3-(heteroaryl)propyl amines 2-7. Compounds 8-12 were evaluated in vitro, in P388 murine lymphocytic leukemia cell line (P388) using SRB assay for cytotoxicity and in adriamycin resistant P388 murine lymphocytic leukemia cell line (P388/ADR) using MTT assay for resistant reversal activity. Compounds 8-12 were non-toxic at lower dose of 20 μg/ml, and effectively reversed adriamycin resistance. However, at higher doses (40, 80 μg/ml) they showed significant cytotxicity and hence reversal potency was not determined at these concentrations.
- Lokhande, Tushar Narendra,Viswanathan, Chelakara Lakshmann,Juvekar, Aarti Shashikant
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body text
p. 894 - 896
(2009/08/15)
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- 2-aminobenzoxazole derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminobenzoxazole derivative compounds of the following formula: wherein R1 to R4 and Z have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminobenzoxazole derivative compounds.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Rhodium-catalysed hydroformylation and carbonylation of N-alkenyl-1,3-diaminopropanes
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The rhodium catalysed reactions of N-alkenyl-1,3-diaminopropanes with H2/CO usually give mixtures of diazabicycloalkanes and aminopropyl lactams. The chemo- and regioselectivity of these reactions are influenced by the choice of ligand and by the ratio of H2 and CO in the gas mixture and in some cases formation of a single compound can be achieved.
- Bergmann, David J.,Campi, Eva M.,Jackson, W. Roy,McCubbin, Quentin J.,Patti, Antonio F.
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p. 17449 - 17460
(2007/10/03)
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- Control of chemo- and regio-selectivity in rhodium catalysed reaction of unsaturated amines with H2/CO
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The rhodium catalysed reactions of N-allyl- and N-butenyl-1.3-diaminopropanes give single products arising from exclusive hydroformylation at the terminal carbon when the hindered bisphosphite ligand, BIPHEPHOS is used. Reactions using a high carbon monoxide : hydrogen ratio (9 : 1) and triphenylphosphine as ligand give predominantly lactams arising from carbonylation but with poor control of regioselectivity.
- Bergmann, David J.,Campi, Eva M.,Jackson, W. Roy,McCubbin, Quentin J.,Patti, Antonio F.
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p. 4315 - 4318
(2007/10/03)
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