- PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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The invention relates to novel heteroaryl compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cardiovascular diseases, and methods treating sepsis or septic shock, using the novel heterocyclic compounds disclosed herein.
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- PCSK9 INHIBITORS AND METHODS OF USE THEREOF
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The invention relates to a novel inhibitor pharmacophore of PCSK9 and heteroaryl compounds that bind the PCSK9 protein.
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Page/Page column 146-147
(2020/07/31)
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- STING MODULATOR COMPOUNDS, AND METHODS OF MAKING AND USING
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The present disclosure provides STING modulators/agonists, and methods of synthesis and methods for using for the prophylaxis or treatment of cancer and other STING-related diseases. The present disclosure relates to a compound represented by the Formula (I): wherein each symbol is as defined in the description, or a pharmaceutically acceptable salt thereof.
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- Preparation method of optical pure cyclopentene alcohol serving as medical intermediate
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The invention relates to a preparation method of optical pure cyclopentene alcohol serving as a medical intermediate. The preparation method comprises the following steps: by taking 3-butenal and a 3-bit or 4-bit derivative thereof as raw materials, synthesizing an optical pure hydroxyaldehyde condensation product under the existence of a catalytic amount of (S)-proline, reducing an aldehyde group into a hydroxyl group, protecting the hydroxyl group with benzyl bromide, and performing efficient double-bond translocation closed loop reaction, thus obtaining (1S, 2R)-2-benzoxymethylcyclopentyl-3-alkene-1-alcohol. According to the method provided by the invention, reaction conditions are mild, the raw materials and reagents are low in cost and readily available, the yield is high, and the method is suitable for industrial production.
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- The synthesis of possible transition state analogue inhibitors of thymidine phosphorylase
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The synthetically challenging SN2 transition state mimic for thymidine phosphorylase, along with its phosphonate analogue, were synthesised via a modified Corey-Link reaction in good overall yields and ensuring the correct stereochemical outcome.
- Evans, Gary B.,Gainsford, Graeme J.,Schramm, Vern L.,Tyler, Peter C.
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p. 406 - 409
(2015/04/27)
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- N-O bond as a glycosidic-bond surrogate: Synthetic studies toward polyhydroxylated N-alkoxypiperidines
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A series of novel polyhydroxylated N-alkoxypiperidines has been synthesized by ring-closing double reductive amination (DRA) of highly functionalized 1,5-dialdehydes with various hydroxylamines. The required saccharide-based dialdehydes were prepared efficiently from sodium cyclopentadienylide in seven steps. A two-step protocol has been developed for the DRA; it led, after deprotection, to isofagomine, 3-deoxyisofagomine, and numerous other N-alkoxy analogues. The barrier to inversion in these polyhydroxylated N-alkoxypiperidine derivatives was found by variable-temperature NMR methods to be approximately 15 kcal mol-1. With the exception of N-hydroxyisofagomine itself, none of the compounds prepared showed significant inhibitory activity against sweet almond β-glucosidase. Copyright
- Malik, Ga?lle,Ferry, Angélique,Guinchard, Xavier,Cresteil, Thierry,Crich, David
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p. 2168 - 2179
(2013/03/29)
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- Asymmetric synthesis of polyhydroxylated N -alkoxypiperidines by ring-closing double reductive amination: Facile preparation of isofagomine and analogues
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A de novo synthesis of novel polyhydroxylated N-alkoxypiperidines based on the ring-closing double reductive amination of 1,5-dialdehydes, obtained by oxidative cleavage of cyclopentene derivatives, with O-substituted hydroxylamines is reported. Isofagomine was accessed by cleavage of the N-O bond of an N-alkoxypiperidine.
- Malik, Gaelle,Guinchard, Xavier,Crich, David
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p. 596 - 599
(2012/02/16)
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- Properties of oligonucleotide with phenyl-substituted carbocyclic nucleoside analogs for the formation of duplex and triplex DNA
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(1S,3S,4R)-1-Phenyl-1-thymidyl-3-hydroxy-4-hydroxymethylcyclopentane (10) and their analogs were synthesized, incorporated into the oligodeoxynucleotides, and their properties were evaluated for the formation of duplex and triplex DNA. The known chiral cyclopentanone derivative was converted into the corresponding ketimine sulfonamide derivative, which was subjected to a stereoselective PhLi addition. The formed sulfonamide was hydrolyzed to afford the primary amino group, on which the thymine moiety was built. The benzyl protecting groups were removed to form the nucleoside analog having a phenyl group and the thymine unit at the 1 position of a carbocyclic skeleton (10). In the estimation of the oligodeoxynucleotides incorporating 10 for duplex and triplex formation, the carbocyclic nucleoside analog 10 did not show the stabilizing effect for duplex formation; on the other hand, it stabilized the triplex. Therefore, the skeleton of the phenyl-substituted carbocyclic nucleoside analog 10 may be a platform for the formation of stable triplex DNA.
- Nasr, Tamer,Taniguchi, Yosuke,Takaki, Tomoko,Okamura, Hidenori,Sasaki, Shigeki
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p. 841 - 860
(2013/02/23)
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- Synthesis of [13C4]Baraclude (entecavir)
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Entecavir, labeled as 1H-[13C4]purin-6(9H)-one, was prepared from commercially available [13C]guanidine HCl, 1 and diethyl [1,2,3-13C3]malonate, 2. The reagents were condensed together to give 2-amino-4,6-dichloro[2,4,5,6-13C 4]pyrimidine 3, which in turn was coupled to an optically active amino cyclopentanol derivative, 9. A further sequence of eight reaction steps completed the constructions of the purine ring system and the exocyclic olefin attachment on the cyclic pentyl portion, 18. The removal of the methoxide and benzyl protecting groups gave [13C4]entecavir, 20 in an overall yield of 6.8%. The chemical purity of the title compound was determined by HPLC to be 99.23%. The percent isotopic [13C4] abundance was found by mass spectral analysis to be 96.7%. No detectable level of the unlabeled entecavir was found by LC-MS analysis. Copyright
- Tran, Scott B.,Ekhato, Ihoezo V.,Rinehart, J. Kent
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scheme or table
p. 485 - 489
(2010/07/04)
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- Novel 3′-deoxy analogs of the anti-HBV agent entecavir: Synthesis of enantiomers from a single chiral epoxide
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A synthesis of novel 3′-deoxy analogs of the anti-HBV agent entecavir (BMS-200475) was devised using regioselective ring opening of suitable cyclopentene epoxides as the key step. This versatile approach afforded access to an enantiomeric pair of carbocyclic nucleosides from a single chiral intermediate.
- Ruediger, Edward,Martel, Alain,Meanwell, Nicholas,Solomon, Carola,Turmel, Brigitte
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p. 739 - 742
(2007/10/03)
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- New convergent synthesis of carbocyclic nucleoside analogues
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Two convergent approaches towards the synthesis of carbocyclic nucleoside analogs will be described. Both approaches start from the stereochemically pure cyclopentenol 8 that has been prepared enantioselectively from an alkylated cyclopentadiene. Using these approaches, carbocyclic analogues of dT, FdU and BVdU have been prepared. Moreover, the conversion into the cycloSalpronucleotide and the corresponding nucleotide will be presented for one example.
- Ludek, Olaf R.,Meier, Chris
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p. 2101 - 2109
(2007/10/03)
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- Stereoselective synthesis of 3-substituted 2-aminocyclopentanecarboxylic acid derivatives and their incorporation into short 12-helical β-peptides that fold in water
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A stereoselective synthetic route is reported for the introduction of side chains at the 3-position of trans-2-aminocyclopentanecarboxylic acid (ACPC). Ring opening of the aziridine 2-benzyloxymethyl-6-azabicyclo[3.1.0]hexane with selected nucleophiles occurs in a regioselective manner and provides ACPC precursors with functional groups at the 3-position, trans to the 2-amino group. Oligomers composed of the 3-substituted ACPC residues maintain the 12-helical conformation displayed by the nonsubstituted analogues, as shown by their similar circular dichroism signatures. The added diversity of the new residues provides good dispersion of NMR signals, allowing the assignment of nearly all the NOE signals of a selected hexamer in aqueous solution. The NOEs between protons on nonadjacent residues are characteristic of the 12-helix. 3-Substituted ACPC residues allow one to arrange specific functional groups in a geometrically defined fashion, which should facilitate the design of β-peptides for biological applications.
- Woll, Matthew G.,Fisk, John D.,LePlae, Paul R.,Gellman, Samuel H.
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p. 12447 - 12452
(2007/10/03)
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- BMS-200475, a novel carbocyclic 2'-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro
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BMS-200475, a never carbocyclic analog of 2'-deoxyguanosine, is a potent inhibitor of hepatitis B virus in vitro (ED50 = 3 nM) with relatively low cytotoxicity (CC50 = 21-120 μM). A practical 10-step asymmetric synthesis was developed affording BMS-200475 in 18% overall chemical yield and > 99% optical purity. The enantiomer of BMS-200475 as well as the adenine, thymine, and iodouracil analogs are much less active.
- Bisacchi,Chao,Bachard,Daris,Innaimo,Jacobs,Kocy,Lapointe,Martel,Merchant,Slusarchyk,Sundeen,Young,Colonno,Zahler
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p. 127 - 132
(2007/10/03)
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- Hydroxymethyl (methylenecyclopentyl) purines and pyrimidines
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Antiviral activity is exhibited by compounds having the formula STR1 and its pharmaceutically acceptable salts.
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- Use of Diethylaminosulphur Trifluoride (DAST) in the Preparation of Synthons of Carbocyclic Nucleosides
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Diethylaminosulphur trifluoride (DAST) converted the protected amino triol (4) into the fluorine-containing compounds (8) and (10).The same reagent converted the alcohol (9) into compounds (10), (5), and (11) and transformed the azido alcohol (15) into the fluoroazides (16) and (19).The fluorinated compounds (5), (8), and (16) are useful synthons for fluorocarbocyclic nucleosides.The effect of neighbouring groups on the course of some DAST reactions is discussed.
- Biggadike, Keith,Borthwick, Alan D.,Evans, Derek,Exall, Anne M.,Kirk, Barrie E.,et al.
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p. 549 - 554
(2007/10/02)
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