Discovery of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides as small molecule inhibitors of PCSK9.


:A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier lead structures.


Bioorg Med Chem Lett


Londregan AT,Aspnes G,Limberakis C,Loria PM,McClure KF,Petersen DN,Raymer B,Ruggeri RB,Wei L,Xiao J,Piotrowski DW




Has Abstract


2018-12-15 00:00:00














  • Submonomer synthesis of azapeptide ligands of the Insulin Receptor Tyrosine Kinase domain.

    abstract::Azapeptide ligands of the Insulin Receptor Tyrosine Kinase (IRTK) were developed by solid-phase submonomer azapeptide synthesis in sufficient isolated yields (36-55%) and purities >95% for structure-activity relationship studies. The azapeptides adopted folded geometries with some proportion of random coil according t...

    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Kurian LA,Silva TA,Sabatino D

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  • Nitrone derivatives of trolox as neuroprotective agents.

    abstract::Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities com...

    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Balogh GT,Vukics K,Könczöl A,Kis-Varga A,Gere A,Fischer J

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  • Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent.

    abstract::A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cushman M,Insaf S,Ruell JA,Schaeffer CA,Rice WG

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  • Identification of arylsulfonamides as ExoU inhibitors.

    abstract::ExoU is a potent virulence factor of Pseudomonas aeruginosa and is considered a potential therapeutic target. In order to discover novel ExoU inhibitors, we screened an in-house chemical library utilizing a yeast-based screening system. Some sulfonamides displayed significant activity without nonspecific cytotoxicity....

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kim D,Baek J,Song J,Byeon H,Min H,Min KH

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  • Antimalarial activity of ferrocenyl chalcones.

    abstract::A series of ferrocenyl chalcones were synthesized and evaluated for in vitro antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum. The most active compounds were 1-(3-pyridyl)-3-ferrocenyl-2-propen-1-one (6) and 1-ferrocenyl-3-(4-nitrophenyl)-2-propen-1-one (28) with IC(50) of 4.5 and ...

    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Wu X,Wilairat P,Go ML

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  • Synthesis and antitumor activity of cyclodepsipeptide zygosporamide and its analogues.

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Wang Y,Zhang F,Zhang Y,Liu JO,Ma D

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  • 1-[(Benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles - potent competitive inhibitors of aromatase.

    abstract::The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles is described. The compounds were tested for human placental aromatase inhibition in vitro, using [1beta-3H]-androstenedione as the substrate for the aromatase enzyme, the percentage inhibition and IC50 data is included. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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  • Recent encounters with atropisomerism in drug discovery.

    abstract::Atropisomerism is stereochemistry arising from restricted bond rotation that creates a chiral axis. Atropisomers are subject to time-dependent inversion of chirality via bond rotation, a property which in drug molecules introduces complexity and challenges for drug discovery and development processes. Greater recognit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审


    authors: Glunz PW

    更新日期:2018-01-15 00:00:00

  • Differential modulation of the antifungal activity of amphotericin B by natural and ent-cholesterol.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Richter RK,Mickus DE,Rychnovsky SD,Molinski TF

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  • Uridine phosphorylase inhibitors: chemical modification of benzyloxybenzyl-barbituric acid and its effects on urdpase inhibition.

    abstract::5-(o-Benzyloxy)benzylbarbituric acid (6) and 5-(p-benzyloxy)benzylbarbituric acid (7) were prepared and their inhibitory activities compared to 5-(m-benzyloxy)-benzylbarbituric acid (BBB) a known, potent inhibitor of uridine phosphorylase (UrdPase). Compounds 6 and 7 were 18-fold and 51-fold less active, respectively,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Guerin DJ,Mazeas D,Musale MS,Naguib FN,Al Safarjalani ON,el Kouni MH,Panzica RP

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    abstract::A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and the cis-configuration of the olefinic bond was restricted by th...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ashraf M,Shaik TB,Malik MS,Syed R,Mallipeddi PL,Vardhan MVPSV,Kamal A

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  • Compelling P1 substituent affect on metalloprotease binding profile enables the design of a novel cyclohexyl core scaffold with excellent MMP selectivity and HER-2 sheddase inhibition.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

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  • Synthesis of 3-[4-(dimethylamino)phenyl]alkyl-2-oxindole derivatives and their effects on neuronal cell death.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Furuta K,Kawai Y,Mizuno Y,Hattori Y,Koyama H,Hirata Y

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Lau CK,Bayly CI,Gauthier JY,Li CS,Therien M,Asante-Appiah E,Cromlish W,Boie Y,Forghani F,Desmarais S,Wang Q,Skorey K,Waddleton D,Payette P,Ramachandran C,Kennedy BP,Scapin G

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  • Trifluoromethylation of flavonoids and anti-tumor activity of the trifluoromethylated flavonoid derivatives.

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Wang CL,Li HQ,Meng WD,Qing FL

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  • Non-peptide alphavbeta3 antagonists. Part 6: design and synthesis of alphavbeta3 antagonists containing a pyridone or pyrazinone central scaffold.

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    journal_title:Bioorganic & medicinal chemistry letters

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    authors: Breslin MJ,Duggan ME,Halczenko W,Fernandez-Metzler C,Hunt CA,Leu CT,Merkle KM,Naylor-Olsen AM,Prueksaritanont T,Stump G,Wallace A,Rodan SB,Hutchinson JH

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Napier SE,Letourneau JJ,Ansari N,Auld DS,Baker J,Best S,Campbell-Wan L,Chan JH,Craighead M,Desai H,Goan KA,Ho KK,Hulskotte EG,MacSweeney CP,Milne R,Morphy JR,Neagu I,Ohlmeyer MH,Peeters AW,Presland J,Riviello C,

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Peel M,Scribner A

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Liu YR,Luo JZ,Duan PP,Shao J,Zhao BX,Miao JY

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kim KH,Moon E,Kim HK,Oh JY,Kim SY,Choi SU,Lee KR

    更新日期:2012-10-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee J,Kang SU,Kim SY,Kim SE,Kang MK,Jo YJ,Kim S

    更新日期:2001-04-23 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhang Z,Zheng G,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Palmer WS,Alam M,Arzeno HB,Chang KC,Dunn JP,Goldstein DM,Gong L,Goyal B,Hermann JC,Hogg JH,Hsieh G,Jahangir A,Janson C,Jin S,Ursula Kammlott R,Kuglstatter A,Lukacs C,Michoud C,Niu L,Reuter DC,Shao A,Silva T,Tr

    更新日期:2013-03-01 00:00:00

  • Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA-0008) as potent and selective ALK inhibitors for anticancer treatment.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Park CH,Choe H,Jang IY,Kwon SY,Latif M,Lee HK,Lee HJ,Yang EH,Yun JI,Chae CH,Cho SY,Choi SU,Ha JD,Jung H,Kim HR,Kim P,Lee CO,Yun CS,Lee K

    更新日期:2013-11-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Han W,Hu Z,Jiang X,Decicco CP

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    abstract::Two thermostable α-carbonic anhydrases (α-CAs) isolated from thermophilic Sulfurihydrogenibium spp., namely SspCA (from S. yellowstonensis) and SazCA (from S. azorense), were shown in a previous work to possess interesting complementary properties. SspCA was shown to have an exceptional thermal stability, whereas SazC...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: De Simone G,Monti SM,Alterio V,Buonanno M,De Luca V,Rossi M,Carginale V,Supuran CT,Capasso C,Di Fiore A

    更新日期:2015-05-01 00:00:00