- Toward an understanding of the chemical etiology for DNA minor-groove recognition by polyamides
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Crescent-shaped polyamides composed of aromatic amino acids, i.e., 1-methyl-1H-imidazole Im, 1-methyl-1H-pyrrole Py, and 3-hydroxy-1H-pyrrole Hp, bind in the minor groove of DNA as 2:1 and 1:1 ligand/DNA complexes. DNA-Sequence specificity can be attributed to shape-selective recognition and the unique corners or pairs of corners presented by each heterocycle(s) to the edges of the base pairs on the floor of the minor groove. Here we examine the relationship between heterocycle structure and DNA-sequence specificity for a family of five-membered aromatic amino acids. By means of quantitative DNase-I footprinting, the recognition behavior of polyamides containing eight different aromatic amino acids, i.e., 1-methyl-1H-pyrazole Pz, 1H-pyrrole Nh, 5-methylthiazole Nt, 4-methylthiazole Th, 3-methylthiophene Tn, thiophene Tp, 3-hydroxythiophene Ht, and furan Fr, were compared with the polyamides containing the parent-ring amino acids Py, Im, and Hp for their ability to discriminate between the four Watson - Crick base pairs in the DNA minor groove. Analysis of the data and molecular modeling showed that the geometry inherent to each heterocycle plays a significant role in the ability of polyamides to differentiate between DNA sequences. Binding appears sensitive to changes in curvature complementarity between the polyamide and DNA. The Tn/Py pair affords a modest 3-fold discrimination of T · A vs. A · T and suggests that an S-atom in the thiophene ring prefers to lie opposite T not A.
- Marques, Michael A.,Doss, Raymond M.,Urbach, Adam R.,Dervan, Peter B.
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Read Online
- Monolithic Silica Support for Immobilized Catalysis in Continuous Flow
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Monolithic and packed-bed reactors featuring immobilized catalysts are well-precedented in continuous flow synthesis but can suffer from adverse pressure drops during use due to their small pore sizes and/or structural changes. Herein, we overcome this challenge with the synthesis of a structurally robust silica-based monolith featuring pore sizes on the millimeter scale. The 3-dimensional solid support structure is constructed from a polystyrene foam-based template and features a functional group handle that can be modified to display a reactive catalyst. Here we functionalize the support with palladium(0) for hydrogenation reactions and a modified proline catalyst for the alpha functionalization of aldehydes. Both reactors showed good activity and excellent catalytic longevity when utilized under continuous flow conditions. (Figure presented.).
- Russell, M. Grace,Veryser, Cedrick,Hunter, James F.,Beingessner, Rachel L.,Jamison, Timothy F.
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supporting information
p. 314 - 319
(2019/12/24)
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- Diarylamide compound and application thereof
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The invention discloses a use of a diarylamide compound with a structure shown as a formula (I), and a pharmaceutically acceptable salt thereof in the preparation of a medicine serving as a urea transporter inhibitor, and the novel diarylamide compound. T
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Paragraph 0317-0320
(2020/12/31)
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- IMIDAZOTHIADIAZOLE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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The present invention provides imidazothiadiazole compounds of Formula (I) wherein A, B, D, Rx, R1, R2, R3, X1, X2 and s are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments.
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Paragraph 00260
(2013/11/18)
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- Palladium-catalyzed silane/siloxane reductions in the one-pot conversion of nitro compounds into their amines, hydroxylamines, amides, sulfonamides, and carbamates
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A combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS) facilitates the room-temperature reduction of aromatic nitro compounds to anilines. These reactions tend to be quick (30 min), high-yielding, and tolerate a range of other functional groups. Replacement of PMHS/KF with triethylsilane allows for the reduction of aliphatic nitro compounds to their corresponding hydroxylamines. Depending on the substrate, both conditions can allow for the in situ conversion of the product amines into amides, sulfonamides, and carbamates. Georg Thieme Verlag Stuttgart.
- Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
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p. 3316 - 3340
(2008/09/17)
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- Pd-catalyzed silicon hydride reductions of aromatic and aliphatic nitro groups
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(Chemical Equation Presented) Room-temperature reduction of aromatic nitro groups to amines can be accomplished in high yield, with wide functional group tolerance and short reaction times (30 min) using a combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS). Replacing PMHS/KF with triethylsilane allows aliphatic nitro groups to be reduced to their hydroxylamines.
- Rahaim Jr., Ronald J.,Maleczka Jr., Robert E.
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p. 5087 - 5090
(2007/10/03)
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- Heterocyclic self-immolative linkers and conjugates
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The present invention provides heterocyclic linker compounds useful for linking drug moieties to ligands. The compounds also include drug-ligand conjugates comprising a ligand capable of targeting a selected cell population, and a drug connected to the li
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Page/Page column 30
(2008/06/13)
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- Diels-Alder Reaction of 2-Amino-Substituted Furans as a Method for Preparing Substituted Anilines
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5-Amino-2-furancarboxylic acid methyl ester undergoes a facile Diels-Alder cycloaddition with a variety of dienophiles to afford ring-opened cycloadducts that are readily dehydrated using BF3-OEt2 to give polysubstituted anilines. In each case, the cycloaddition proceeds with high regioselectivity, with the electron-withdrawing group being located ortho to the amino group. The most favorable FMO interaction is between the HOMO of the furanamine and the LUMO of the dienophile. The atomic coefficient at the ester carbon of the furan is larger than that at the amino center, and this nicely accommodates the observed regioselectivity. The [4 + 2]-cycloaddition of N-(5-nitrofuranyl)morpholine with methyl vinyl ketone affords a mixture of three phenols. One of the phenols is derived from a Diels - Alder reaction followed by nitro group ejection and subsequent aromatization. The remaining two phenols are the result of cleavage of the initially formed oxabicyclic intermediate with concomitant migration of the nitro group. The mild reaction conditions with which furan-2-carbamic acid tert-butyl ester undergoes Diels - Alder cycloaddition with N-phenylmaleimide allow for the ready isolation of the initial oxybridged cycloadduct.
- Padwa, Albert,Dimitroff, Martin,Waterson, Alex G.,Wu, Tianhua
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p. 4088 - 4096
(2007/10/03)
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- Disubstituted aryl and heteroaryl imines having retinoid-like biological activity
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Compounds of the formula STR1 wherein the R 1 groups independently are hydrogen, lower alkyl, or two geminal R 1 groups jointly represent an oxo ( O) or a thio ( S) group; R 2 is hydrogen or lower alkyl, or halogen; M is or --N CR 4 -- or --R 4 C N-- where R 4 is hydrogen or lower alkyl; X is C(R 1) 2 ; Y is phenyl optionally substituted with an R 3 group which is lower alkyl or halogen; A is (CH 2) n where n is 0-5, lower branched chain alkyl, cycloalkyl, alkenyl, alkynyl; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8, CONR 9 R 10, --CH 2 OH, CH 2OR 11, CH 2 OCOR 11, CHO, CH(OR 12) 2, CHOR 13 O, --COR 7, CR 7 (OR 12) 2, or CR 7 OR 13 O, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons have retinoid-like biological activity.
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- Synthesis of polysubstituted anilines using the Diels-Alder reaction of methyl 5-aminofuroate
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Methyl 5-aminofuroate undergoes a facile [4+2]-cycloaddition with a variety of dienophiles to afford ring opened cycloadducts which are readily dehydrated using BF3·OEt2 to give polysubstituted anilines.
- Cochran, John E.,Wu, Tianhua,Padwa, Albert
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p. 2903 - 2906
(2007/10/03)
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- A practical synthesis of 5-(chloromethyl)furo[2,3-b]pyridine, a key intermediate for the HIV protease inhibitor, L-754,394
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A practical synthesis of 5-(chloromethyl)furo[2,3-b]pyridine (10), the side chain used to incorporate a key pharmacophore of the HIV protease inhibitor, L-754,394, is described. The synthesis was accomplished in ten steps and in 15% overall yield from com
- Bhupathy,Conlon,Wells,Nelson,Reider,Rossen,Sager,Volante,Dorsey,Hoffman Jr.,Joseph,McDaniel
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p. 1283 - 1287
(2007/10/03)
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