- Synthesis of [14C]- and [13C6]-labeled potent HIV non-nucleoside reverse transcriptase inhibitor
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5,11-Dihydro-11-ethyl-5-methyl-8-{2-{(1-oxido-4-quinolinyl)oxy}ethyl} -6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one, (1), labeled with carbon-14 in the quinoline-benzene ring, in one of the pyridine rings of the dipyridodiazepinone tricyclic moiety, and in the side chain, was prepared in three different syntheses with specific activities ranging from 44 to 47 mCi/mmol (1.63-1.75 GBq/mmol). In the first synthesis, 5,11-dihydro-11-ethyl-8- (2-hydroxyethyl)-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4] diazepin-6-one (2) was coupled to 4-hydroxyquinoline, [benzene- 14C(U)]-, using Mitsunobu's reaction conditions, followed by the oxidation of the quinoline nitrogen with 3-chloroperoxybenzoic acid to give ([14C]-(1a)) in 43% radiochemical yield. Second, 3-amino-2- chloropyridine, [2,6-14C]-, was used to prepare 8-bromo-5,11-dihydro- 11-ethyl-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (8), and then Stille coupled to allyl(tributyl)tin followed by ozonolysis of the terminal double bond and in situ reduction of the resulting aldehyde to alcohol (10). Mitsunobu etherification and oxidation as seen before gave ([ 14C]-(1b)) in eight steps and in 11% radiochemical yield. Finally, carbon-14 potassium cyanide was used to prepare isopropyl cyanoacetate (12), which was used to transform bromide (8) to labeled aryl acetic acid (13) under palladium catalysis. Trihydroborane reduction of the acid gave alcohol (14) labeled in the side chain, which was used as described above to prepare ([ 14C]-(1c)) in 4.3% radiochemical yield. The radiochemical purities of these compounds were determined by radio-HPLC and radio-TLC to be more than 98%. To prepare [13C6]-(1), [13C 6]-4-hydroxyquinoline was prepared from [13C 6]-aniline and then coupled to (2) and oxidized as seen before. Copyright
- Latli, Bachir,Hrapchak, Matt,Busacca, Carl A.,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
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- HETEROARYL COMPOUNDS AS NECROSIS INHIBITORS, COMPOSITION AND METHOD USING THE SAME
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The present disclosure provides heteroaryl compounds of Formula (I), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from or related to necrosis. Formula (I) i
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Paragraph 00189-00191
(2020/07/25)
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- MITOCHONDRIAL ALDEHYDE DEHYDROGENASE 2 (ALDH2) BINDING POLYCYCLIC AMIDES AND THEIR USE FOR THE TREATMENT OF CANCER
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The present invention provides compounds of formula I that bind to mitochondrial aldehyde dehydrogenase-2 (ALDH2), and methods of using said compounds to treat patients with i.a. cancer, Fanconi anemia and alcohol-related disorders. [Formula should be ins
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Page/Page column 148
(2015/09/28)
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- Iridium-catalyzed C-H borylation of heteroarenes: Scope, regioselectivity, application to late-stage functionalization, and mechanism
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A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were found to be amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodology for the synthesis of complex heteroaryl structures. Application of this methodology to the synthesis and late-stage functionalization of biologically active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen.
- Larsen, Matthew A.,Hartwig, John F.
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supporting information
p. 4287 - 4299
(2014/04/03)
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- HETEROCYCLIC COMPOUNDS AS INHIBITORS OF FATTY ACID BIOSYSNTHESIS FOR BACTERIAL INFECTIONS
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The present invention relates to novel heterocyclic compounds which specifically inhibit bacterial FabI and can be used for the treatment of Staphylococcal infections.
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Paragraph 0086; 0087; 0101
(2014/09/16)
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- 6-Benzylamino 4-oxo-1,4-dihydro-1,8-naphthyridines and 4-oxo-1,4- dihydroquinolines as HIV integrase inhibitors
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SAR studies on the quinolone carboxylic acid class of HIV-1 integrase inhibitors focused on improving the metabolic stability and led to the discovery of 27 and 38.
- Nagasawa, Johnny Y.,Song, Jenny,Chen, Huanming,Kim, Hong-Woo,Blazel, Julie,Ouk, Samedy,Groschel, Bettina,Borges, Virginia,Ong, Voon,Yeh, Li-Tain,Girardet, Jean-Luc,Vernier, Jean-Michel,Raney, Anneke K.,Pinkerton, Anthony B.
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scheme or table
p. 760 - 763
(2011/03/18)
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- Synthesis of [14C]- and [13C6]-labeled potent HIV non-nucleoside reverse transcriptase inhibitor
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Compound 1 (Figure 1), labeled with carbon-14 in the quinoline-benzene ring, in one of the pyridine rings of the dipyridodiazepinone tricyclic moiety, and in the side chain, was prepared in three different syntheses with specific activities ranging from 4
- Latli, Bachir,Hrapchak, Matt,Busacca, Carl A.,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
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scheme or table
p. 446 - 448
(2011/05/05)
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- SPIRO CONDENSED BARBITURIC ACID DERIVATIVES FOR USE AS ANTIBACTERIAL
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In one aspect, the present invention relates to compounds of Formula (I): to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to method for their preparation.
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Page/Page column 70
(2009/03/07)
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- Development of a pilot-plant process for a nevirapine analogue HIV NNRT inhibitor
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The pilot-plant synthesis of nevirapine analogue 1 is described. The compound was prepared in eight steps from substituted pyridine raw materials and 4-hydroxyquinoline. The key transformation involves a novel one-pot conversion of an arylhalide to arylac
- Busacca, Carl A.,Cerreta, Mike,Dong, Yong,Eriksson, Magnus C.,Farina, Vittorio,Feng, XuWu,Kim, Ji-Young,Lorenz, Jon C.,Sarvestani, Max,Simpson, Robert,Varsolona, Rieh,Vitous, Jana,Campbell, Scot J.,Davis, Mark S.,Jones, Paul-James,Norwood, Daniel,Qiu, Fenghe,Beaulieu, Pierre L.,Duceppe, Jean-Simon,Hache, Bruno,Brong, Jim,Chiu, Fang-Ting,Curtis, Tom,Kelley, Jason,Lo, Young S.,Powner, Tory H.
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p. 603 - 613
(2013/01/03)
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- MET kinase inhibitors
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The present invention is directed to compounds having the formula I or II: including salts thereof, and methods for using them for the treatment of cancer.
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Page/Page column 40-41
(2008/06/13)
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- MACROLONE COMPOUNDS
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A compound of formula (I) compositions comprising same, processes for their preparation and use of said compounds, particularly in the treatment of microbial infections.
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Page/Page column 51
(2008/06/13)
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- MACROLONES - AMINO SUBSTITUTED QUINOLONES
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Compounds of formula (I) or pharmaceutically acceptable derivatives thereof having antimicrobial activity are disclosed, as are processes for their preparation, compositions containing them and their use in medicine.
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Page/Page column 59-60
(2010/11/30)
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- Non-nucleoside reverse transcriptase inhibitors
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Disclosed are compounds of formula I: wherein R2 is H, halogen, (C1-4)alkyl, O(C1-4)alkyl, NH(C1-4alkyl) or N(C1-4alkyl)2; R4 is H or CH3; R5 is H or CH3; R12 is H, halogen, (C1-4)alkyl, CF3, or NO2; R13 is H, (C1-4)alkyl, halogen, OH, or NH2, with the proviso that R12 and R13 are not both H; and R14 is COOR14a wherein R14a is H or (C1-6)alkyl; or R14 is (C2-4)alkenyl-COOR14a wherein R14a is as defined herein; or R14 is (C1-4)alkyl-COOR14a wherein R14a is as defined above; or a salt or a prodrug thereof, useful as inhibitors of HIV reverse transcriptase.
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- Fused polycyclic pyranyl compounds as antiviral agents
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Novel polycyclic pyranyl compounds, pharmaceutical compositions, and their use as anti-viral agents are disclosed.
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- Some Methyl 2,5- and 5,6-Dihalonicotinates
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The preparation of the methyl esters of eight dihalonicotinic acids is described.The esters were synthesized either by the methanolysis of their respective acid chlorides or by treatment of the appropriate acid with diazomethane in ether.Experimental and spectral data for the methyl dihalonicotinates are presented.
- Setliff, Frank L.,Hule, W. Reeves
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p. 332 - 333
(2007/10/02)
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